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Cheng Z, Liu D, Park JY, Meng X, Yang Y, Dang M, Dai X, Yang J, Yuan M, Li M, Wang L, Huang Y, Wang J, Liang Y, Fei W. Evaluation of the management of rotator cuff injuries utilising superparamagnetic iron oxide tracking stem cells. Tissue Cell 2025; 95:102836. [PMID: 40081255 DOI: 10.1016/j.tice.2025.102836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 02/11/2025] [Accepted: 03/01/2025] [Indexed: 03/15/2025]
Abstract
BACKGROUND The ultrastructure of the tendon-bone interface (TBI) is inherently complex. After arthroscopic reconstruction, it is often replaced by disorganized scar tissue, which increases the risk of re-tearing.Stem cell therapies offer a promising approach to regenerate the original tissue structure and enhance the healing environment. The effectiveness of these therapies depends on understanding the localization, proliferation, and overall behavior of the implanted stem cells. This study aimed to track the distribution of stem cells in a rat model of rotator cuff injury using Magnetic Resonance Imaging (MRI) and superparamagnetic iron oxide nanoparticles (SPIO) and to evaluate the mechanisms and therapeutic effects of stem cell therapy. METHODS Adipose-derived mesenchymal stem cells (ADSCs) were isolated and expanded, then labeled with SPIO at an optimized concentration. The visibility of these labeled cells was assessed via MRI, along with evaluations of their viability, potential toxicity, and migration capacity in vitro.For the in vivo study, rats with rotator cuff tears were divided into two groups: a control group that received a PBS injection, and a treatment group that received SPIO-labeled ADSCs (designated as S-A). MRI scans were conducted at 1, 2, and 4 weeks post-surgery, followed by histological analysis after the rats were euthanized. At 8 weeks post-surgery, rats were sacrificed, and their shoulder joints were analyzed biomechanically and histologically to assess the overall treatment efficacy. RESULTS SPIO nanoparticles were successfully incorporated into ADSCs, and MRI imaging demonstrated that these SPIO-labeled cells significantly enhanced MRI contrast without affecting cell viability, proliferation, or migration ability. Both MRI and histological analyses confirmed that the implanted stem cells survived and remained localized for at least two weeks. Further histological and biomechanical evaluations indicated that the stem cells facilitated the repair of the TBI. This repair process appeared to be mediated by an increase in M2 macrophage activity within the injured tissue, promoting improved local healing conditions. CONCLUSION This study confirms that labeling ADSCs with SPIO nanoparticles is an effective method for tracking these cells in vivo using MRI, providing a non-invasive approach to monitor the repair of injured TBI. Moreover, the localized survival of transplanted stem cells supports their role in enhancing TBI repair by modulating the local inflammatory response.
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Affiliation(s)
- Ziang Cheng
- Department of Orthopedics and Sports Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, P. R. China
| | - Dianwei Liu
- The Yangzhou school of clinical medicine of Dalian Medical University, Dalian 116000, P. R. China
| | - Jin-Young Park
- Center for Shoulder, Elbow and Sports, Neon Orthopaedic Clinic, Seoul, Republic of Korea
| | - Xiangji Meng
- The Yangzhou school of clinical medicine of Dalian Medical University, Dalian 116000, P. R. China
| | - Yuxia Yang
- Department of Orthopedics and Sports Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, P. R. China
| | - Mengbo Dang
- The Yangzhou school of clinical medicine of Dalian Medical University, Dalian 116000, P. R. China
| | - Xiaomei Dai
- Department of Orthopedics and Sports Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, P. R. China
| | - Jian Yang
- Department of Orthopedics and Sports Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, P. R. China
| | - Meijuan Yuan
- Department of Orthopedics and Sports Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, P. R. China
| | - Mingjun Li
- Department of Orthopedics and Sports Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, P. R. China
| | - Liang Wang
- Department of Orthopedics and Sports Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, P. R. China
| | - Yao Huang
- Department of Orthopedics and Sports Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, P. R. China
| | - Jingcheng Wang
- Department of Orthopedics and Sports Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, P. R. China.
| | - Yuan Liang
- Department of Orthopedics and Sports Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, P. R. China.
| | - Wenyong Fei
- Department of Sports Medicine, Northern Jiangsu People's Hospital, Yangzhou 225001, P. R. China; Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, P. R. China.
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Vieira Ferreira N, Andrade R, Pinto Freitas T, de Campos Azevedo C, Espregueira-Mendes J, Salgado AJ, Sevivas N. The role of injections of mesenchymal stem cells as an augmentation tool in rotator cuff repair: a systematic review. JSES REVIEWS, REPORTS, AND TECHNIQUES 2025; 5:231-242. [PMID: 40321851 PMCID: PMC12047555 DOI: 10.1016/j.xrrt.2024.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/08/2025]
Abstract
Background Arthroscopic repair is currently the gold standard for the surgical treatment of rotator cuff tears, but the retear rates remain unacceptably high. Mesenchymal stem cells (MSCs) may play a role in the local biology and enhance tendon-to-bone healing during rotator cuff repair. However, the scientific literature is still not well systematized on the effects of injection of MSCs as an augmentation tool for rotator cuff repair. Our goal was to investigate the effect of injections of MSCs to augment rotator cuff repair in patients with rotator cuff tear. Methods PubMed and EMBASE were searched up to June 2022 for clinical studies that applied MSCs injections to augment rotator cuff repair. Imaging, patient-reported outcomes measures, shoulder range of motion and strength were collected. Quantitative synthesis included within- and between-group mean differences with the within-group percentage of minimal clinically important difference for each study and continuous outcomes, and relative risks (RR) for retears and adverse events. Quantitative synthesis was computed with 95% confidence intervals (CIs). Results We included 5 studies comprising a total of 228 individuals with a weighted mean age of 59.3 ± 1.2 years. Three studies used bone marrow MSCs and two studies applied adipose-derived MSCs. Patient-reported outcomes measures, shoulder range of motion, and strength improved significantly in all MSCs groups, with minimal clinically important differences ranging from 120% to 679% of established cut-off. When compared to rotator cuff repair alone, the MSCs groups did not result in improved outcomes. The MSCs group showed significant protective effect at the mid-term (RR = 0.52, 95% CI 0.27-0.98) and long-term (RR = 0.24, 95% CI 0.11-0.53). Conclusion There are no differences in clinical and functional outcomes between rotator cuff repair with or without augmentation with MSCs. However, there may be a protective effect against retear at the mid-term and long-term follow-up when augmenting the repair with MSCs. The literature on this topic is still preliminary and the quality and certainty of evidence is limited.
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Affiliation(s)
- Nuno Vieira Ferreira
- Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal
- ICVS/3B’s, PT Government Associate Laboratory, Braga/Guimarães, Portugal
- Hospital de Santa Maria Maior Barcelos, Barcelos, Portugal
- Hospital dos Lusíadas Braga, Braga, Portugal
- Instituto de Investigação em Ortopedia e Medicina Desportiva, Braga, Portugal
| | - Renato Andrade
- Clínica Espregueira - FIFA Medical Centre of Excellence, Porto, Portugal
- Dom Henrique Research Centre, Porto, Portugal
- Porto Biomechanics Laboratory (LABIOMEP), University of Porto, Porto, Portugal
| | - Tânia Pinto Freitas
- Hospital de Santa Maria Maior Barcelos, Barcelos, Portugal
- Hospital dos Lusíadas Braga, Braga, Portugal
- Instituto de Investigação em Ortopedia e Medicina Desportiva, Braga, Portugal
| | | | - João Espregueira-Mendes
- ICVS/3B’s, PT Government Associate Laboratory, Braga/Guimarães, Portugal
- Clínica Espregueira - FIFA Medical Centre of Excellence, Porto, Portugal
- Dom Henrique Research Centre, Porto, Portugal
- School of Medicine, University of Minho, Braga, Portugal
- 3B’s Research Group – Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal
| | - António J. Salgado
- Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal
- ICVS/3B’s, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Nuno Sevivas
- Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal
- ICVS/3B’s, PT Government Associate Laboratory, Braga/Guimarães, Portugal
- School of Medicine, University of Minho, Braga, Portugal
- Trofa Saúde Group, Vila do Conde, Portugal
- Centro Hospitalar Médio Ave, Famalicão, Portugal
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Han SC, Han J, Kim YK, Hyun MJ, Jeong HJ, Oh JH. Bone Marrow Aspirate Concentrate Combined With an Appropriate Carrier Effectively Promotes Bone-Tendon Interface Healing in a Rabbit Model of Chronic Rotator Cuff Tear. Am J Sports Med 2025; 53:600-611. [PMID: 39876035 DOI: 10.1177/03635465241313124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2025]
Abstract
BACKGROUND The efficacy of bone marrow aspirate concentrate (BMAC) in promoting bone-tendon interface (BTI) healing without any carriers remains a subject of debate. PURPOSE To evaluate BMAC effects with different carriers on tendon regeneration in a rabbit model of chronic rotator cuff tear. STUDY DESIGN Controlled laboratory study. METHODS In vitro, the amount of growth factor and the differentiation potential of BMAC with different carriers (polydeoxyribonucleotide [PDRN] and atelocollagen [ATC]) were assessed. In vivo, 64 rabbits were randomly allocated into 4 groups. Different materials were injected into the repair site according to the allocated group: control, saline; BMAC, BMAC and saline; BMAC-PDRN, BMAC with PDRN; BMAC-ATC, BMAC with ATC (n = 16 in each). Genetic and histologic analyses were conducted at 4 and 12 weeks after repair, while biomechanical evaluations were performed at 12 weeks after repair. RESULTS In vitro, the degree of multilineage differentiation was much stronger using BMAC with ATC as compared with administration of BMAC alone or BMAC with PDRN (P < .001). In vivo, the BMAC-ATC group had the highest levels of aggrecan expression, bone morphogenetic protein 2, and collagen type I alpha 1 among all groups (all P < .001) at 4 weeks after repair. Furthermore, the BMAC-ATC group showed collagen fiber continuity, denser collagen fibers, and more mature BTI as compared with the other groups (all P < .001) at 12 weeks after repair. Concurrently, the BMAC-ATC group also demonstrated significantly higher load-to-failure versus the remaining groups (all P < .001) at 12 weeks after repair. CONCLUSION Local application of BMAC without appropriate carriers could not enhance BTI healing. However, BMAC with 2 different carriers effectively accelerated BTI healing, particularly in the ATC environment. Therefore, the combination of BMAC and ATC may act as a powerful biological agent to promote healing after rotator cuff repair in a chronic rotator cuff tear model using rabbits. CLINICAL RELEVANCE Local application of BMAC without appropriate carriers could not enhance BTI healing. However, the combination of BMAC and ATC may synergistically promote rotator cuff tendon healing.
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Affiliation(s)
- Sheng Chen Han
- Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Jian Han
- Department of Orthopaedic Surgery, The First People's Hospital of Huzhou, First Affiliated Hospital of Huzhou University, Huzhou, China
| | - Young Kyu Kim
- Department of Orthopaedic Surgery, Bundang Jesaeng Hospital, Seongnam, Republic of Korea
| | - Myung Jae Hyun
- Department of Orthopaedic Surgery, Yonsei the Baro Hospital, Siheung, Republic of Korea
| | - Hyeon Jang Jeong
- Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Joo Han Oh
- Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
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Christogiannis IF, Mastrokalos DS, Papagelopoulos PJ, Lakiotaki E, Karatrasoglou E, Bami M, Milonaki M, Koulalis D. The addition of mesenchymal stem cells in a bioabsorbable scaffold does not enhance tendon healing after a repair of rotator cuff tear. Knee Surg Sports Traumatol Arthrosc 2025; 33:707-715. [PMID: 39077836 DOI: 10.1002/ksa.12385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Revised: 07/03/2024] [Accepted: 07/08/2024] [Indexed: 07/31/2024]
Abstract
PURPOSE The purpose of the study is to evaluate the healing potential of a full-thickness tendon defect in the rotator cuff of rabbits using a bioabsorbable scaffold impregnated with bone marrow-mesenchymal stem cells (BM-MSCs) or rotator cuff-derived mesenchymal stem cells (RC-MSCs). METHODS Sixteen adult rabbits were subjected to a full-thickness rotator cuff deficit. Rabbits were randomly assigned to four groups of four animals. In Group 0 (control), the deficit was left untreated. In Group 1, the deficit was treated with a single synthetic scaffold alone. In Group 2, the deficit was treated with the previous scaffold loaded with allogeneic BM-MSCs. In Group 3, the deficit was treated with the previous scaffold loaded with allogenic RC-MSCs. After animal sacrifice, tissue samples were subjected to histological and immunohistochemical analysis. RESULTS Group 1 showed the highest mean tendon maturing score (15.3 ± 0.9) postoperatively, being significantly higher, in comparison to groups 0, 2 and 3 (p = 0.01, 0.02 and 0.01, respectively). Group 1 showed the highest mean collagen I/collagen III ratio (1.4 ± 0.8) postoperatively but without any statistical significance. CONCLUSIONS The utilization of MSCs in rotator cuff repair in a rabbit model has not been associated with an enhancement in tendon healing in 16 weeks postoperatively, in comparison to controls and bioabsorbable scaffolds. The addition of MSCs does not result in better rotator cuff healing. LEVEL OF EVIDENCE Not applicable. This is an animal study.
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Affiliation(s)
- Ioannis F Christogiannis
- 1st Department of Orthopaedic Surgery, School of Medicine, Attikon University General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios S Mastrokalos
- 1st Department of Orthopaedic Surgery, School of Medicine, Attikon University General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Panayiotis J Papagelopoulos
- 1st Department of Orthopaedic Surgery, School of Medicine, Attikon University General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Eleftheria Lakiotaki
- 1st Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Eleni Karatrasoglou
- 1st Department of Oncology, Saint Savvas Anticancer Hospital, Athens, Greece
| | - Myrto Bami
- 'Panayotis N. Soucacos' Orthopaedic Research and Education Center (OREC), Attikon University General Hospital, Athens, Greece
| | - Mandy Milonaki
- 'Panayotis N. Soucacos' Orthopaedic Research and Education Center (OREC), Attikon University General Hospital, Athens, Greece
| | - Dimitrios Koulalis
- 1st Department of Orthopaedic Surgery, School of Medicine, Attikon University General Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Jiang X, Xu C, Yuan C, Gao W, Liu W, Wang Y, Wang H, Yu W, He Y. The Effect of Postoperative Tranexamic Acid and Dexamethasone on Quality of Recovery After Arthroscopic Rotator Cuff Repair: a Double-Blinded, Randomized Controlled Trial. J Pain Res 2025; 18:259-270. [PMID: 39867540 PMCID: PMC11759578 DOI: 10.2147/jpr.s497297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 01/13/2025] [Indexed: 01/28/2025] Open
Abstract
PURPOSE Arthroscopic rotator cuff repair (ARCR) commonly results in significant postoperative pain. Adjuncts like dexamethasone (DEX) and tranexamic acid (TXA) are used to enhance postoperative recovery. This study aimed to determine whether the combined application of TXA and DEX could improve postoperative recovery during the first 24 hours in ARCR patients. Our goal is to relieve the acute postoperative pain and promote fast recovery and rapid discharge for ARCR patients. PATIENTS AND METHODS Ninety-six patients who underwent ARCR from December 2023 to March 2024 were enrolled in this double-blinded, randomized control trial (Registration number, ChiCTR2300078507). Patients were randomized to intravenously receive 200mL of normal saline (control group), 200mL of 1g TXA in saline (TXA group), or 200 mL of 1g TXA and 5mg DEX in saline (TXA+DEX group) within 2 hours postoperatively. The primary outcome was the Quality of Recovery-15 (QoR-15) score at 24 hours post-surgery. Secondary outcomes included mean visual analog scale (VAS) scores every four hours within 24 hours, postoperative blood test results the day after surgery, and American Shoulder and Elbow Surgeons (ASES) score at 3 months postoperatively. RESULTS No significant differences in QoR-15 scores at 24 hours were observed among the groups [control, 127.0 (112.8, 138.0); TXA, 125.0 (116.5, 136.8); TXA+DEX, 132.0 (120.3, 140.8), p = 0.176]. VAS scores at 5-8 (placebo vs TXA+DEX, p = 0.014; TXA vs TXA+DEX, p = 0.002), 9-12 (placebo vs TXA+DEX, p = 0.008; TXA vs TXA+DEX, p < 0.001), and 13-16 (placebo vs TXA+DEX, p = 0.035; TXA vs TXA+DEX, p = 0.013) hours postoperatively showed a significant decrease for the TXA+DEX group compared with the control or TXA group. There were no significant differences in postoperative blood test results and ASES score at 3 months postoperatively. CONCLUSION Postoperative application of TXA alone could not facilitate postoperative recovery during the first 24 hours in ARCR patients. Although the combination of TXA and DEX presented better levels of postoperative pain between 5 and 16 hours than the control and TXA alone, it did not significantly improve postoperative recovery quality. Further large-scale and multi-center investigation is required to determine if the combined application of TXA and DEX or TXA alone is beneficial for postoperative recovery in ARCR patients.
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Affiliation(s)
- Xiping Jiang
- Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China
| | - Cheng Xu
- Department of Anesthesiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China
| | - Chenrui Yuan
- Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China
| | - Wenliang Gao
- Department of Orthopedics, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, 364000, People’s Republic of China
| | - Wencai Liu
- Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China
| | - Yifei Wang
- Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China
| | - Haiming Wang
- Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China
| | - Weilin Yu
- Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China
| | - Yaohua He
- Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China
- Department of Orthopedic Surgery, Jinshan District Central Hospital Affiliated to Shanghai University of Medicine & Health Sciences, Jinshan Branch of Shanghai Sixth People’s Hospital, Shanghai, 201500, People’s Republic of China
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Trapana J, Weinerman J, Lee D, Sedani A, Constantinescu D, Best TM, Hornicek FJ, Hare JM. Cell-based therapy in the treatment of musculoskeletal diseases. Stem Cells Transl Med 2024; 13:959-978. [PMID: 39226104 PMCID: PMC11465182 DOI: 10.1093/stcltm/szae049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 05/21/2024] [Indexed: 09/04/2024] Open
Abstract
A limited number of tissues can spontaneously regenerate following injury, and even fewer can regenerate to a state comparable to mature, healthy adult tissue. Mesenchymal stem cells (MSCs) were first described in the 1960s-1970s by Friedenstein et al as a small population of bone marrow cells with osteogenic potential and abilities to differentiate into chondrocytes. In 1991, Arnold Caplan coined the term "mesenchymal cells" after identifying these cells as a theoretical precursor to bone, cartilage, tendon, ligament, marrow stroma, adipocyte, dermis, muscle, and connective tissues. MSCs are derived from periosteum, fat, and muscle. Another attractive property of MSCs is their immunoregulatory and regenerative properties, which result from crosstalk with their microenvironment and components of the innate immune system. Collectively, these properties make MSCs potentially attractive for various therapeutic purposes. MSCs offer potential in sports medicine, aiding in muscle recovery, meniscal tears, and tendon and ligament injuries. In joint disease, MSCs have the potential for chondrogenesis and reversing the effects of osteoarthritis. MSCs have also demonstrated potential application to the treatment of degenerative disc disease of the cervical, thoracic, and lumbar spine.
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Affiliation(s)
- Justin Trapana
- Department of Orthopaedics, University of Miami Miller School of Medicine, Miami, United States
- Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, United States
| | - Jonathan Weinerman
- Department of Orthopaedics, University of Miami Miller School of Medicine, Miami, United States
| | - Danny Lee
- Department of Orthopaedics, University of Miami Miller School of Medicine, Miami, United States
| | - Anil Sedani
- Department of Orthopaedics, University of Miami Miller School of Medicine, Miami, United States
| | - David Constantinescu
- Department of Orthopaedics, University of Miami Miller School of Medicine, Miami, United States
| | - Thomas M Best
- Department of Orthopaedics, University of Miami Miller School of Medicine, Miami, United States
- Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, United States
| | - Francis J Hornicek
- Department of Orthopaedics, University of Miami Miller School of Medicine, Miami, United States
- Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, United States
| | - Joshua M Hare
- Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, United States
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Timmer KB, Killian ML, Harley BAC. Paracrine signals influence patterns of fibrocartilage differentiation in a lyophilized gelatin hydrogel for applications in rotator cuff repair. Biomater Sci 2024; 12:4806-4822. [PMID: 39150417 PMCID: PMC11404831 DOI: 10.1039/d4bm00543k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/17/2024]
Abstract
Rotator cuff injuries present a clinical challenge for repair due to current limitations in functional regeneration of the native tendon-to-bone enthesis. A biomaterial that can regionally instruct unique tissue-specific phenotypes offers potential to promote enthesis repair. We have recently demonstrated the mechanical benefits of a stratified triphasic biomaterial made up of tendon- and bone-mimetic collagen scaffold compartments connected via a continuous hydrogel, and we now explore the potential of a biologically favorable enthesis hydrogel for this application. Here we report in vitro behavior of human mesenchymal stem cells (hMSCs) within thiolated gelatin (Gel-SH) hydrogels in response to chondrogenic stimuli as well as paracrine signals derived from MSC-seeded bone and tendon scaffold compartments. Chondrogenic differentiation media promoted upregulation of cartilage and entheseal fibrocartilage matrix markers COL2, COLX, and ACAN as well as the enthesis-associated transcription factors SCX, SOX9, and RUNX2 in hMSCs within Gel-SH. Similar effects were observed in response to TGF-β3 and BMP-4, enthesis-associated growth factors known to play a role in entheseal development and maintenance. Conditioned media generated by hMSCs seeded in tendon- and bone-mimetic collagen scaffolds influenced patterns of gene expression regarding enthesis-relevant growth factors, matrix markers, and tendon-to-bone transcription factors for hMSCs within the material. Together, these findings demonstrate that a Gel-SH hydrogel provides a permissive environment for enthesis tissue engineering and highlights the significance of cellular crosstalk between adjacent compartments within a spatially graded biomaterial.
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Affiliation(s)
- Kyle B Timmer
- Dept. Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, 110 Roger Adams Laboratory, 600 S. Mathews Ave., Urbana, IL 61801, USA.
| | - Megan L Killian
- Department of Orthopaedic Surgery, University of Michigan Ann Arbor, Ann Arbor, Michigan 48109, USA
- Department of Molecular and Integrative Physiology, University of Michigan Ann Arbor, Ann Arbor, Michigan 48109, USA
| | - Brendan A C Harley
- Dept. Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, 110 Roger Adams Laboratory, 600 S. Mathews Ave., Urbana, IL 61801, USA.
- Cancer Center at Illinois, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA
- Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA
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Savoie Iii FH, Delvadia BP, Tate JP, Winter JE, Williams GH, Sherman WF, O'Brien MJ. Biologics in rotator cuff repair. Bone Joint J 2024; 106-B:978-985. [PMID: 39216849 DOI: 10.1302/0301-620x.106b9.bjj-2024-0513.r1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Rotator cuff tears are common in middle-aged and elderly patients. Despite advances in the surgical repair of rotator cuff tears, the rates of recurrent tear remain high. This may be due to the complexity of the tendons of the rotator cuff, which contributes to an inherently hostile healing environment. During the past 20 years, there has been an increased interest in the use of biologics to complement the healing environment in the shoulder, in order to improve rotator cuff healing and reduce the rate of recurrent tears. The aim of this review is to provide a summary of the current evidence for the use of forms of biological augmentation when repairing rotator cuff tears.
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Affiliation(s)
- Felix H Savoie Iii
- Department of Orthopaedic Surgery, Tulane University School of Medicine, New Orleans, Louisiana, USA
- Tulane Doctors-Sports Medicine Plus, University Medical Center New Orleans, Lakeside Hospital, Omega Hospital Surgery Center, East Jefferson Hospital, and Slidell Memorial Hospital, Slidell, Louisiana, USA
| | - Bela P Delvadia
- Department of Orthopaedic Surgery, Tulane University School of Medicine, New Orleans, Louisiana, USA
- Tulane Doctors-Sports Medicine Plus, University Medical Center New Orleans, Lakeside Hospital, Omega Hospital Surgery Center, East Jefferson Hospital, and Slidell Memorial Hospital, Slidell, Louisiana, USA
| | - Jackson P Tate
- Department of Orthopaedic Surgery, Tulane University School of Medicine, New Orleans, Louisiana, USA
- Tulane Doctors-Sports Medicine Plus, University Medical Center New Orleans, Lakeside Hospital, Omega Hospital Surgery Center, East Jefferson Hospital, and Slidell Memorial Hospital, Slidell, Louisiana, USA
| | - Julianna E Winter
- Department of Orthopaedic Surgery, Tulane University School of Medicine, New Orleans, Louisiana, USA
- Tulane Doctors-Sports Medicine Plus, University Medical Center New Orleans, Lakeside Hospital, Omega Hospital Surgery Center, East Jefferson Hospital, and Slidell Memorial Hospital, Slidell, Louisiana, USA
| | - Garrett H Williams
- Department of Orthopaedic Surgery, Tulane University School of Medicine, New Orleans, Louisiana, USA
- Tulane Doctors-Sports Medicine Plus, University Medical Center New Orleans, Lakeside Hospital, Omega Hospital Surgery Center, East Jefferson Hospital, and Slidell Memorial Hospital, Slidell, Louisiana, USA
| | - William F Sherman
- Department of Orthopaedic Surgery, Tulane University School of Medicine, New Orleans, Louisiana, USA
- Tulane Doctors-Sports Medicine Plus, University Medical Center New Orleans, Lakeside Hospital, Omega Hospital Surgery Center, East Jefferson Hospital, and Slidell Memorial Hospital, Slidell, Louisiana, USA
| | - Michael J O'Brien
- Department of Orthopaedic Surgery, Tulane University School of Medicine, New Orleans, Louisiana, USA
- Tulane Doctors-Sports Medicine Plus, University Medical Center New Orleans, Lakeside Hospital, Omega Hospital Surgery Center, East Jefferson Hospital, and Slidell Memorial Hospital, Slidell, Louisiana, USA
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Villarreal-Espinosa JB, Berreta RS, Boden SA, Khan ZA, Carter AJ, Cole BJ, Verma NN. Inlay Scaffold Augmentation of Rotator Cuff Repairs Enhances Histologic Resemblance to Native Enthesis in Animal Studies: A Systematic Review. Arthroscopy 2024:S0749-8063(24)00499-7. [PMID: 39029812 DOI: 10.1016/j.arthro.2024.06.048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 06/21/2024] [Accepted: 06/25/2024] [Indexed: 07/21/2024]
Abstract
PURPOSE To investigate the outcomes of inlay positioned scaffolds for rotator cuff healing and regeneration of the native enthesis after augmentation of rotator cuff tendon repairs in preclinical studies. METHODS A literature search was performed using the PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature databases according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Preclinical studies reporting on outcomes after inlay tendon augmentation in rotator cuff repair were included. Preclinical study quality was assessed using an adapted version of the Gold Standard Publication Checklist for animal studies. The level of evidence was defined based on the inclusion of clinical analyses (grade A), biomechanical analyses (grade B), biochemical analyses (grade C), semiquantitative analyses (grade D), and qualitative histologic analyses (grade E). RESULTS Thirteen preclinical studies met the inclusion criteria. Quality assessment scores ranged from 4 to 8 points, and level-of-evidence grades ranged from B to E. Sheep/ewes were the main animal rotator cuff tear model used (n = 7). Demineralized bone matrix or demineralized cortical bone was the most commonly investigated scaffold (n = 6). Most of the preclinical evidence (n = 10) showed qualitative or quantitative differences regarding histologic, biomechanical, and biochemical outcomes in favor of interpositional scaffold augmentation of cuff repairs in comparison to controls. CONCLUSIONS Inlay scaffold positioning in preclinical studies has been shown to enhance the healing biology of the enthesis while providing histologic similarities to its native 4-zone configuration. CLINICAL RELEVANCE Although onlay positioned grafts and scaffolds have shown mixed results in preclinical and early clinical studies, inlay scaffolds may provide enhanced healing and structural support in comparison owing to the ability to integrate with the bone-tendon interface.
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Affiliation(s)
| | - Rodrigo Saad Berreta
- Department of Orthopaedics, Rush University Medical Center, Chicago, Illinois, U.S.A
| | - Stephanie A Boden
- Department of Orthopaedics, Rush University Medical Center, Chicago, Illinois, U.S.A
| | | | - Andrew J Carter
- Prince of Wales Clinical School, UNSW Medicine at the University of New South Wales, Sydney, Australia
| | - Brian J Cole
- Department of Orthopaedics, Rush University Medical Center, Chicago, Illinois, U.S.A
| | - Nikhil N Verma
- Department of Orthopaedics, Rush University Medical Center, Chicago, Illinois, U.S.A..
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10
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Yozgatli TK, Gelenli Dolanbay E, Cingoz T, Paksoy AE, Uslu U, Ovali E, Kocaoglu B. Satellite myoblast and mesenchymal stem cell injections decrease fatty degeneration after rotator cuff tear in rats. J Exp Orthop 2024; 11:e12087. [PMID: 39050590 PMCID: PMC11267176 DOI: 10.1002/jeo2.12087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 04/30/2024] [Accepted: 05/14/2024] [Indexed: 07/27/2024] Open
Abstract
Purpose Rotator cuff (RC) tears cause fatty degeneration, aggravated by delayed treatment. Surgical repair alone cannot reverse fatty degeneration. It was aimed to test if local injections of satellite cell-derived myoblasts or satellite myoblasts (SM) from the deltoid region and mesenchymal stem cells (MSCs) from the subcutaneous abdominal fat pad would stimulate myogenesis and decrease adipogenesis in the rat model of fatty degenerated RC tear. Methods A standardized RC tear surgery was performed on both shoulders of 24 Wistar albino rats at t = 0, and rats were followed for 8 weeks to create a chronic degeneration model. The animals were randomly divided into repair + SM and MSC (n = 12) or repair only (n = 12) groups. Transosseous repair with or without stem cell-based injection was performed on the right shoulder of all rats on week 8, with additional injections on weeks 9 and 10. The left shoulders were used as control. The animals were followed until week 14 for recovery. Results Histological and histomorphometric analyses were performed in week 14. The repair + SM and MSC group had a significantly greater supraspinatus muscle mass than the repair only and control groups. The adipose tissue ratio was significantly lower in the repair + SM and MSC groups versus the repair only and control groups. Conclusion Histologically, the repair + SM and MSC group had improved muscle and tendon organization. In treating chronically degenerated RC tear in a rat model, surgical repair combined with injections of SM and MSC improved fatty degeneration, tendon healing and myogenesis. Level of Evidence Level III.
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Affiliation(s)
- Tahir Koray Yozgatli
- Department of Orthopedic SurgeryAcibadem University Faculty of MedicineIstanbulTurkey
| | - Elif Gelenli Dolanbay
- Department of Histology and EmbryologyIstanbul Medeniyet University Faculty of MedicineIstanbulTurkey
| | - Tunca Cingoz
- Department of Orthopedic SurgeryAcibadem University Faculty of MedicineIstanbulTurkey
| | - Ahmet Emre Paksoy
- Department of Orthopedic SurgeryAtatürk University Faculty of MedicineErzurumTurkey
| | - Unal Uslu
- Department of Histology and EmbryologyIstanbul Medeniyet University Faculty of MedicineIstanbulTurkey
| | - Ercument Ovali
- Acibadem Labcell Cellular Therapy LaboratoryIstanbulTurkey
| | - Baris Kocaoglu
- Department of Orthopedic SurgeryAcibadem University Faculty of MedicineIstanbulTurkey
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11
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Celikten M, Sahin H, Senturk GE, Bilsel K, Pulatkan A, Kapicioglu M, Sakul BU. The effect of platelet-rich fibrin, platelet-rich plasma, and concentrated growth factor in the repair of full thickness rotator cuff tears. J Shoulder Elbow Surg 2024; 33:e261-e277. [PMID: 37898418 DOI: 10.1016/j.jse.2023.09.028] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 09/11/2023] [Accepted: 09/24/2023] [Indexed: 10/30/2023]
Abstract
BACKGROUND Rotator cuff lesions rank among the prevalent causes of shoulder pain. Combining surgical interventions with growth factors, scaffolds, and stem cell therapies can effectively decrease the likelihood of rotator cuff repair recurrence. Platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and concentrated growth factor (CGF), isolated from blood and rich in growth factors, have a critical role in cell migration, cell proliferation, and angiogenesis during the tissue regeneration process. Investigations have further substantiated the beneficial impact of PRP and PRF on the biomechanical and histologic attributes of the tendon-bone interface. We aimed to investigate the effectiveness of CGF compared with PRF and PRP in the repair of rotator cuff lesions as a new treatment strategy. METHODS Incision was performed on both shoulder regions of 21 adult rabbits. After 8 weeks, both shoulders of the rabbits were repaired by suturing. PRF and CGF were administered to 2 separate groups along with the repair. Tissues were collected for biomechanical measurements and histologic evaluations. RESULTS Histologically, CGF, PRF, and PRP showed similar results to the healthy control group. The level of improvement was significant in the PRF and PRP groups. In the PRF group, the distribution of Ki67 (+), CD31 (+), and CD34 (+) cells was determined intensely in the tendon-bone junction regions. Apoptotic cells increased significantly in the repair group compared with the healthy group, whereas fewer apoptotic cells were found in the PRF-, PRP-, and CGF-applied groups. In the biomechanical results, no statistical difference was recorded among the groups. CONCLUSION The use of PRF, PRP, and CGF in rotator cuff repair shows promise in shortening the treatment period and preventing the recurrence of rotator cuff lesions.
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Affiliation(s)
- Mert Celikten
- Department of Anatomy, Health Sciences Institute, Istanbul Medipol University, Istanbul, Turkey.
| | - Hakan Sahin
- Department of Histology and Embryology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey
| | - Gozde Erkanli Senturk
- Department of Histology and Embryology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey
| | - Kerem Bilsel
- Department of Orthopaedics and Traumatology, Acibadem Mehmet Ali Aydinlar University, Faculty of Medicine, Istanbul, Turkey
| | - Anil Pulatkan
- Department of Orthopedics and Traumatology, School of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Mehmet Kapicioglu
- Department of Orthopedics and Traumatology, School of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Bayram Ufuk Sakul
- Department of Anatomy, School of Medicine, Istanbul Medipol University, Istanbul, Turkey
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12
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Pang L, Yao L, Wang Z, Li T, Li Y, Zhang C, Tang X. Bone Marrow Stimulation Does Not Lead to Lower Retear Rates, Better Functional Outcomes, or Higher Complication Rates at Short-Term Follow-Up for Arthroscopic Rotator Cuff Repair: A Meta-analysis of Randomized Controlled Trials. Arthroscopy 2024; 40:1453-1472. [PMID: 38922600 DOI: 10.1016/j.arthro.2023.10.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 10/12/2023] [Accepted: 10/20/2023] [Indexed: 06/27/2024]
Abstract
PURPOSE To determine the effect of bone marrow stimulation (BMS) on retear rates, functional outcomes, and complication rates in patients who underwent arthroscopic rotator cuff repair (RCR) through a meta-analysis of randomized controlled trials. METHODS PubMed, EMBASE, Web of Science, and The Cochrane Library were searched on March 25, 2023. Two evaluators independently screened the literature, extracted data, and assessed the methodologic quality of the enrolled studies. Meta-analysis was conducted using RevMan software, version 5.4. RESULTS A total of 7 randomized controlled trials with 638 patients were included. The evaluation of rotator cuff tendon integrity was conducted using distinct imaging modalities. Specifically, 259 patients underwent magnetic resonance imaging whereas 208 patients underwent ultrasound. Additionally, a subset of 95 patients underwent either of these modalities; however, the precise distribution between these 2 modalities was not explicitly delineated. Compared with RCR alone, RCR combined with BMS provided similar retear rates (P = .51, I2 = 46%), Constant-Murley scores (P = .14, I2 = 0%), American Shoulder and Elbow Surgeons (standardized shoulder assessment form) scores (P = .56, I2 = 0%), Western Ontario Rotator Cuff Index scores (P = .20, I2 = 0%), visual analog scale scores (P = .19, I2 = 0%), forward flexion (P = .18, I2 = 0%), external rotation (P = .62, I2 = 0%), severe complication rates (P = .56, I2 = 0%), and mild complication rates (P = .10, I2 = 0%). CONCLUSIONS Compared with the outcomes observed after isolated arthroscopic RCR, arthroscopic RCR with BMS showed comparable results in terms of retear rate, functional outcomes, and incidence of complications. LEVEL OF EVIDENCE Level II, meta-analysis of Level I and II studies.
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Affiliation(s)
- Long Pang
- Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China
| | - Lei Yao
- Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China
| | - Zining Wang
- West China Medical School, Sichuan University, Chengdu, China
| | - Tao Li
- Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China
| | - Yinghao Li
- Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China
| | - Chunsen Zhang
- Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China
| | - Xin Tang
- Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China.
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13
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Eshima K, Ohzono H, Gotoh M, Abe R, Nakamura H, Mitsui Y, Hiraoka K, Okawa T. Effects of adipose-derived cell supplementation on tendon-bone healing in a rat model of chronic rotator cuff tear with suprascapular nerve injury. J Int Med Res 2024; 52:3000605241232550. [PMID: 38456645 PMCID: PMC10924565 DOI: 10.1177/03000605241232550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 01/29/2024] [Indexed: 03/09/2024] Open
Abstract
OBJECTIVE To investigate the effect of adipose-derived cells (ADCs) on tendon-bone healing in a rat model of chronic rotator cuff tear (RCT) with suprascapular nerve (SN) injury. METHODS Adult rats underwent right shoulder surgery whereby the supraspinatus was detached, and SN injury was induced. ADCs were cultured from the animals' abdominal fat. At 6 weeks post-surgery, the animals underwent surgical tendon repair; the ADC (+ve) group (n = 18) received an ADC injection, and the ADC (-ve) group (n = 18) received a saline injection. Shoulders were harvested at 10, 14, and 18 weeks and underwent histological, fluorescent, and biomechanical analyses. RESULTS In the ADC (+ve) group, a firm enthesis, including dense mature fibrocartilage and well-aligned cells, were observed in the bone-tendon junction and fatty infiltration was less than in the ADC (-ve) group. Mean maximum stress and linear stiffness was greater in the ADC (+ve) compared with the ADC (-ve) group at 18 weeks. CONCLUSION ADC supplementation showed a positive effect on tendon-bone healing in a rat model of chronic RCT with accompanying SN injury. Therefore, ADC injection may possibly accelerate recovery in massive RCT injuries.
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Affiliation(s)
- Kenichiro Eshima
- Department of Orthopedic Surgery, Social insurance Tagawa Hospital, 10-18 kamihon-machi, Tagawa, Fukuoka 826-0023, Japan
| | - Hiroki Ohzono
- Department of Orthopedic Surgery, Kurume University Medical Center, 151-1 Kokubu-machi, Kurume, Fukuoka 839-0863, Japan
| | - Masafumi Gotoh
- Department of Orthopedic Surgery, Kurume University Medical Center, 151-1 Kokubu-machi, Kurume, Fukuoka 839-0863, Japan
| | - Ryunosuke Abe
- Department of Orthopedic Surgery, Kurume University Medical Center, 151-1 Kokubu-machi, Kurume, Fukuoka 839-0863, Japan
| | - Hidehiro Nakamura
- Department of Orthopedic Surgery, Kurume University Medical Center, 151-1 Kokubu-machi, Kurume, Fukuoka 839-0863, Japan
| | - Yasuhiro Mitsui
- Department of Orthopedic Surgery, Hyakutake Hospital, 4-2-15 mizugae, Saga city, Saga 840-0054, Japan
| | - Koji Hiraoka
- Department of Orthopedic Surgery, Kurume University Hospital, 67 Asahi-machi, Kurume Fukuoka 830-0011, Japan
| | - Takahiro Okawa
- Department of Orthopedic Surgery, Kurume University Medical Center, 151-1 Kokubu-machi, Kurume, Fukuoka 839-0863, Japan
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14
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Park JM, Han SH, Cho BC, Lee SM, Shin MS, Yu JH, Kim HJ, Noh HD, Cho MS, Kim MK. Enhancing Post-Surgical Rehabilitation Outcomes in Patients with Chronic Ankle Instability: Impact of Subtalar Joint Axis Balance Exercises Following Arthroscopic Modified Broström Operation. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:328. [PMID: 38399615 PMCID: PMC10890246 DOI: 10.3390/medicina60020328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 02/08/2024] [Accepted: 02/11/2024] [Indexed: 02/25/2024]
Abstract
Background and Objectives: This study aimed to evaluate the effects of subtalar joint axis-based balance exercises on the anterior talofibular ligament (ATFL) thickness, ankle strength, and ankle stability after an arthroscopic modified Broström operation (AMBO) for chronic ankle instability (CAI). Materials and Methods: The study included 47 patients diagnosed with CAI who underwent AMBO and were randomly divided into three groups: control (n = 11), general balance exercise (n = 17), and subtalar joint axis balance exercise (n = 19), regardless of the affected area. Participants in the exercise rehabilitation group performed exercises for 60 min twice a week for six weeks, starting six weeks after AMBO. ATFL thickness, ankle strength, and ankle dynamic stability were measured using musculoskeletal ultrasonography, Biodex, and Y-balance test, respectively, before and after treatment. Results: Compared with the remaining groups, the subtalar joint axis balance exercise group had reduced ATFL thickness (p = 0.000), improved ankle strength for eversion (p = 0.000) and inversion (p = 0.000), and enhanced ankle stability (p = 0.000). Conclusions: The study results suggest that subtalar joint axis-based balance exercises may contribute to the early recovery of the ankle joint after AMBO.
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Affiliation(s)
- Ji-Myeong Park
- Sports Medical Research Center, Daechan Hospital, 590 Inju-daero, Namdong-gu, Incheon 21570, Republic of Korea; (J.-M.P.); (S.-H.H.); (H.-D.N.)
| | - Sang-Ho Han
- Sports Medical Research Center, Daechan Hospital, 590 Inju-daero, Namdong-gu, Incheon 21570, Republic of Korea; (J.-M.P.); (S.-H.H.); (H.-D.N.)
| | - Byeong-Chae Cho
- Nowon Samsung Orthopedics, 456 Nohae-ro, Nowon-gu, Seoul 01762, Republic of Korea; (B.-C.C.); (S.-M.L.)
| | - Se-Min Lee
- Nowon Samsung Orthopedics, 456 Nohae-ro, Nowon-gu, Seoul 01762, Republic of Korea; (B.-C.C.); (S.-M.L.)
| | - Mal-Soon Shin
- Department of Global Sport Studies, Korea University, 2511 Sejong-ro, Jochiwon-eup, Sejong 30019, Republic of Korea;
| | - Jae-Ho Yu
- Department of Physical Therapy, Sunmoon University, 70, Seonmun-ro 221beon-gil, Tangjeong-myeon, Asan-si 31460, Republic of Korea;
| | - Ho-Jin Kim
- Department of Sports and Exercise Medicine, Biomedical Science, Korea University, 2511 Sejong-ro, Jochiwon-eup, Sejong 30019, Republic of Korea; (H.-J.K.); (M.-S.C.)
| | - Hyun-Dong Noh
- Sports Medical Research Center, Daechan Hospital, 590 Inju-daero, Namdong-gu, Incheon 21570, Republic of Korea; (J.-M.P.); (S.-H.H.); (H.-D.N.)
| | - Min-Suk Cho
- Department of Sports and Exercise Medicine, Biomedical Science, Korea University, 2511 Sejong-ro, Jochiwon-eup, Sejong 30019, Republic of Korea; (H.-J.K.); (M.-S.C.)
| | - Myung-Ki Kim
- Department of Global Sport Studies, Korea University, 2511 Sejong-ro, Jochiwon-eup, Sejong 30019, Republic of Korea;
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15
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Ponz-Lueza V, Lopiz Y, Rodríguez-Bobada C, Tornero-Esteban P, Arvinius C, García-Fernández C, Seara-Lifante D, Rojo-Pérez FJ, Marco F. Efficacy of transplantation of lipoaspired mesenchymal stem cells in the treatment of chronic rotator cuff tears. Experimental model in rats. Rev Esp Cir Ortop Traumatol (Engl Ed) 2024; 68:9-17. [PMID: 37230410 DOI: 10.1016/j.recot.2023.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 05/17/2023] [Accepted: 05/18/2023] [Indexed: 05/27/2023] Open
Abstract
BACKGROUND AND AIM Rotator cuff tears emerge in approximately 30% of the population over 60 years of age. Arthroscopic surgical treatment of these lesions is the treatment of choice, however, despite the improved repair techniques, the rate of re-tears ranges between 11 and 94%. Therefore, researchers seek to improve the biological healing process through the use of different alternatives such as mesenchymal stem cells (MSCs). Our objective is to evaluate the efficacy of a Cellular Therapy Drug made from allogeneic stem cells derived from adipose tissue in a rat model of chronic rotator cuff injury. MATERIAL AND METHODS The supraspinatus lesion was created in 48 rats for subsequent suturing at 4 weeks. MSCs in suspension were added to 24 animals after suturing, and HypoThermosol-FRS® (HTS) to 24 animals as a control group. Histology (Åström and Rausing scale) and the maximum load, displacement and elastic constant of the supraspinatus tendon were analyzed in both groups 4 months after the repair. RESULTS No statistically significant differences were found in the histological score comparing the tendons treated with MSCs with respect to the tendons treated with HTS (P=.811) nor in the results of maximum load (P=.770), displacement (P=.852) or elastic constant (P=.669) of the tendon in both groups. CONCLUSIONS The addition of adipose-derived cells in suspension to the repair of a chronic cuff injury does not improve the histology or biomechanics of the sutured tendon.
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Affiliation(s)
- V Ponz-Lueza
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Clínico San Carlos, Madrid, España.
| | - Y Lopiz
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Clínico San Carlos, Universidad Complutense, Madrid, España
| | - C Rodríguez-Bobada
- Unidad de Medicina y Cirugía Experimental, Hospital Clínico San Carlos, Madrid, España
| | - P Tornero-Esteban
- Instituto de Investigación Sanitaria, Hospital Clínico San Carlos (IdISSC), Madrid, España
| | - C Arvinius
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Clínico San Carlos, Madrid, España
| | - C García-Fernández
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Clínico San Carlos, Madrid, España
| | - D Seara-Lifante
- Departamento de Ciencia de Materiales, Universidad Politécnica de Madrid, Centro de Tecnología Biomédica, Madrid, España; Univerdad Politécnica, Silk Biomed S.L., Madrid, España
| | | | - F Marco
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Clínico San Carlos, Universidad Complutense, Madrid, España
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16
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Ponz-Lueza V, Lopiz Y, Rodríguez-Bobada C, Tornero-Esteban P, Arvinius C, García-Fernández C, Seara-Lifante D, Rojo-Pérez FJ, Marco F. [Translated article] Efficacy of transplantation of lipoaspired mesenchymal stem cells in the treatment of chronic rotator cuff tears. Experimental model in rats. Rev Esp Cir Ortop Traumatol (Engl Ed) 2024; 68:T9-T17. [PMID: 37992858 DOI: 10.1016/j.recot.2023.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 05/18/2023] [Indexed: 11/24/2023] Open
Abstract
BACKGROUND AND AIM Rotator cuff tears emerge in approximately 30% of the population over 60 years of age. Arthroscopic surgical treatment of these lesions is the treatment of choice, however, despite the improved repair techniques, the rate of re-tears ranges between 11 and 94%. Therefore, researchers seek to improve the biological healing process through the use of different alternatives such as mesenchymal stem cells (MSCs). Our objective is to evaluate the efficacy of a cellular therapy drug made from allogeneic stem cells derived from adipose tissue in a rat model of chronic rotator cuff injury. MATERIAL AND METHODS The supraspinatus lesion was created in 48 rats for subsequent suturing at 4 weeks. MSCs in suspension were added to 24 animals after suturing, and HypoThermosol-FRS® (HTS) to 24 animals as a control group. Histology (Åström and Rausing scale) and the maximum load, displacement and elastic constant of the supraspinatus tendon were analysed in both groups 4 months after the repair. RESULTS No statistically significant differences were found in the histological score comparing the tendons treated with MSCs with respect to the tendons treated with HTS (P=0.811) nor in the results of maximum load (P=0.770), displacement (P=0.852) or elastic constant (P=0.669) of the tendon in both groups. CONCLUSIONS The addition of adipose-derived cells in suspension to the repair of a chronic cuff injury does not improve the histology or biomechanics of the sutured tendon.
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Affiliation(s)
- V Ponz-Lueza
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Clínico San Carlos, Madrid, Spain.
| | - Y Lopiz
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Clínico San Carlos, Universidad Complutense, Madrid, Spain
| | - C Rodríguez-Bobada
- Unidad de Medicina y Cirugía Experimental, Hospital Clínico San Carlos, Madrid, Spain
| | - P Tornero-Esteban
- Instituto de Investigación Sanitaria, Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - C Arvinius
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Clínico San Carlos, Madrid, Spain
| | - C García-Fernández
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Clínico San Carlos, Madrid, Spain
| | - D Seara-Lifante
- Departamento de Ciencia de Materiales, Universidad Politécnica de Madrid, Centro de Tecnología Biomédica, Madrid, Spain; Univerdad Politécnica, Silk Biomed S.L., Madrid, Spain
| | | | - F Marco
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Clínico San Carlos, Universidad Complutense, Madrid, Spain
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17
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von Witzleben M, Hahn J, Richter RF, de Freitas B, Steyer E, Schütz K, Vater C, Bernhardt A, Elschner C, Gelinsky M. Tailoring the pore design of embroidered structures by melt electrowriting to enhance the cell alignment in scaffold-based tendon reconstruction. BIOMATERIALS ADVANCES 2024; 156:213708. [PMID: 38029698 DOI: 10.1016/j.bioadv.2023.213708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 11/21/2023] [Accepted: 11/23/2023] [Indexed: 12/01/2023]
Abstract
Tissue engineering of ligaments and tendons aims to reproduce the complex and hierarchical tissue structure while meeting the biomechanical and biological requirements. For the first time, the additive manufacturing methods of embroidery technology and melt electrowriting (MEW) were combined to mimic these properties closely. The mechanical benefits of embroidered structures were paired with a superficial micro-scale structure to provide a guide pattern for directional cell growth. An evaluation of several previously reported MEW fiber architectures was performed. The designs with the highest cell orientation of primary dermal fibroblasts were then applied to embroidery structures and subsequently evaluated using human adipose-derived stem cells (AT-MSC). The addition of MEW fibers resulted in the formation of a mechanically robust layer on the embroidered scaffolds, leading to composite structures with mechanical properties comparable to those of the anterior cruciate ligament. Furthermore, the combination of embroidered and MEW structures supports a higher cell orientation of AT-MSC compared to embroidered structures alone. Collagen coating further promoted cell attachment. Thus, these investigations provide a sound basis for the fabrication of heterogeneous and hierarchical synthetic tendon and ligament substitutes.
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Affiliation(s)
- Max von Witzleben
- Technische Universität Dresden, University Hospital Carl Gustav Carus and Faculty of Medicine, Centre for Translational Bone, Joint and Soft Tissue Research, Fetscherstr. 74, 01307 Dresden, Germany
| | - Judith Hahn
- Leibniz-Institut für Polymerforschung Dresden e. V. (IPF), Institute of Polymer Materials, Hohe Str. 6, 01069 Dresden, Germany
| | - Ron F Richter
- Technische Universität Dresden, University Hospital Carl Gustav Carus and Faculty of Medicine, Centre for Translational Bone, Joint and Soft Tissue Research, Fetscherstr. 74, 01307 Dresden, Germany
| | - Bianca de Freitas
- Technische Universität Dresden, University Hospital Carl Gustav Carus and Faculty of Medicine, Centre for Translational Bone, Joint and Soft Tissue Research, Fetscherstr. 74, 01307 Dresden, Germany
| | - Emily Steyer
- Technische Universität Dresden, University Hospital Carl Gustav Carus and Faculty of Medicine, Centre for Translational Bone, Joint and Soft Tissue Research, Fetscherstr. 74, 01307 Dresden, Germany
| | - Kathleen Schütz
- Technische Universität Dresden, University Hospital Carl Gustav Carus and Faculty of Medicine, Centre for Translational Bone, Joint and Soft Tissue Research, Fetscherstr. 74, 01307 Dresden, Germany
| | - Corina Vater
- Technische Universität Dresden, University Hospital Carl Gustav Carus and Faculty of Medicine, Centre for Translational Bone, Joint and Soft Tissue Research, Fetscherstr. 74, 01307 Dresden, Germany
| | - Anne Bernhardt
- Technische Universität Dresden, University Hospital Carl Gustav Carus and Faculty of Medicine, Centre for Translational Bone, Joint and Soft Tissue Research, Fetscherstr. 74, 01307 Dresden, Germany
| | - Cindy Elschner
- Leibniz-Institut für Polymerforschung Dresden e. V. (IPF), Institute of Polymer Materials, Hohe Str. 6, 01069 Dresden, Germany
| | - Michael Gelinsky
- Technische Universität Dresden, University Hospital Carl Gustav Carus and Faculty of Medicine, Centre for Translational Bone, Joint and Soft Tissue Research, Fetscherstr. 74, 01307 Dresden, Germany.
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Zhou T, Han C, Weng X. Present situation and development prospects of the diagnosis and treatment of rotator cuff tears. Front Surg 2023; 10:857821. [PMID: 37440927 PMCID: PMC10333593 DOI: 10.3389/fsurg.2023.857821] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 05/24/2023] [Indexed: 07/15/2023] Open
Abstract
Rotator cuff tears are an important cause of shoulder pain and are caused by degeneration or trauma of the shoulder tendon at the anatomical neck of the humeral head. The understanding and research of rotator cuff tears have a history of hundreds of years, and their etiology, diagnosis, and treatment have a complete system, but some detailed rules of diagnosis and treatment still have room for development. This research paper briefly introduces the diagnosis and treatment of rotator cuff tears. The current situation and its valuable research direction are described.
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Affiliation(s)
- Tianjun Zhou
- Department of Orthopedic, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
| | - Chang Han
- Department of Orthopedic, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
| | - Xisheng Weng
- Department of Orthopedic, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
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Dai H, Zhang H, Qiu Z, Shi Q. Periosteum-derived skeletal stem cells encapsulated in platelet-rich plasma enhance the repair of bone defect. Tissue Cell 2023; 83:102144. [PMID: 37354707 DOI: 10.1016/j.tice.2023.102144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 06/09/2023] [Accepted: 06/14/2023] [Indexed: 06/26/2023]
Abstract
BACKGROUND Spontaneous restoration of large bone defects remains a challenge under infections, tumors, and crushing conditions. Current stem cell-based therapies for treating bone defects need improvement, because the used stem cells are isolated by a traditional protocol, which is based on their properties of in-vitro plastic adherence and fibroblastic colony formation. The stem cells isolated by the traditional protocol belong to a multicellular type mixture, individual cells vary in proliferative and osteogenic potential. Thus, developing a protocol capable of isolating stem cell subset with higher purity is required and urgent. AIM This study aimed to sort a subpopulation of stem cells from periosteum using flow cytometry (named as FC-PSCs), and evaluate the proliferative and osteogenic capacity of FC-PSCs in-vitro, and then establish a new stem cell-based therapies for treating bone defects by delivering the FC-PSCs within platelet-rich plasma (PRP). METHODS Mouse periosteum was used to sort FC-PSCs using flow cytometry with CD45-TER119-TIE2-ITGAV+CD90 + 6C3-CD105- markers, or isolate periosteum-derived stem cells with the traditional protocol (TP-PSCs) as control. After evaluating the FC-PSCs proliferation and osteogenic differentiation in-vitro as well as the promotive efficacy of platelet-rich plasma (PRP) on FC-PSCs proliferation and osteogenic differentiation, the FC-PSCs were delivered into the femoral epiphysis bone defect site of a mouse model by platelet-rich plasma (PRP). At postoperative 14 or 28 days, these mice were euthanized for harvest the femur specimens for micro-CT, histological evaluation. RESULTS In-vitro results determined that the FC-PSCs showed more capacity for proliferation and osteogenic differentiation compared with the TP-PSCs. In addition, in-vitro results showed the promotive efficacy of PRP on FC-PSCs proliferation and osteogenic differentiation. In-vivo results showed that the FC-PSCs delivered by PRP was able to facilitate the repair of bone defects by stimulating new bone formation and remodeling. CONCLUSION FC-PSCs delivered by PRP enhance the repair of bone defects by stimulating new bone formation and remodeling.
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Affiliation(s)
- Haibo Dai
- Department of Orthopedics (Second ward), Xiangtan Central Hospital, Xiangtan 411199, China; Xiangtan Clinical College, Xiangya Medical School, Central South University, Xiangtan 411199, China
| | - Haici Zhang
- Department of Orthopedics (Second ward), Xiangtan Central Hospital, Xiangtan 411199, China; Xiangtan Clinical College, Xiangya Medical School, Central South University, Xiangtan 411199, China
| | - Zhilong Qiu
- Department of Orthopedics (Second ward), Xiangtan Central Hospital, Xiangtan 411199, China; Xiangtan Clinical College, Xiangya Medical School, Central South University, Xiangtan 411199, China
| | - Qiang Shi
- Department of Spine Surgery, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410018, China; Clinical College of Changsha Central Hospital, Xiangya Medical College, Central South University, Changsha 410018, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
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Song Y, Li P, Xu Y, Lin Z, Deng Z, Chen C. Menstrual Blood-Derived Mesenchymal Stem Cells Encapsulated in Autologous Platelet-Rich Gel Facilitate Rotator Cuff Healing in a Rabbit Model of Chronic Tears. Am J Sports Med 2023:3635465231168104. [PMID: 37184028 DOI: 10.1177/03635465231168104] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/16/2023]
Abstract
BACKGROUND Successful management of chronic rotator cuff (RC) tears remains a challenge owing to its limited intrinsic healing capacity and unsatisfactory failure rate. Menstrual blood-derived mesenchymal stem cells (MenSCs) have the potential to differentiate into the chondrogenic or osteogenic lineage. Autologous platelet-rich gel (APG), a gel material derived from platelet-rich plasma (PRP), can be applied as a carrier system for cell delivery and also as a releasing system for endogenous growth factors. PURPOSE To investigate the effect of human MenSCs encapsulated in APG (MenSCs@APG) on the healing of chronic RC tears in a rabbit model. STUDY DESIGN Controlled laboratory study. METHODS After evaluation of the effect of PRP on MenSC proliferation or differentiation, the stem cells were encapsulated in APG for in vivo injection. Supraspinatus tenotomy from the right greater tuberosity was performed on 45 New Zealand White rabbits. After 6 weeks, these rabbits were randomly allocated to 3 supplemental treatments during supraspinatus repair: saline injection (control [CTL] group), APG injection (APG group), and MenSCs@APG injection (MenSCs@APG group). At week 18, these rabbits were sacrificed to harvest the humerus-supraspinatus tendon complexes for micro-computed tomography (CT), histological evaluation, tensile test, and MenSC tracking. RESULTS In vitro results showed that APG can stimulate MenSC proliferation and enhance chondrogenic or osteogenic differentiation. In vivo results showed that APG can act as a carrier for delivering MenSCs into the healing site, and also as a stimulator for enhancing the in vivo performance of MenSCs. Micro-CT showed that bone volume/total volume and trabecular thickness of the new bone in the MenSCs@APG group presented significantly larger values than those of the APG or CTL group (P < .05 for all). Histologically, compared with the CTL or APG group, significantly more mature fibrocartilage regenerated at the healing site in the MenSCs@APG group. A large number of human nuclei-stained cells were observed in the MenSCs@APG group, presenting a similar appearance to fibrochondrocytes or osteocytes. Biomechanically, the MenSCs@APG group showed significantly higher failure load and stiffness than the APG or CTL group (P < .05 for all). CONCLUSION Human MenSCs@APG facilitated RC healing in a rabbit model of chronic tears. CLINICAL RELEVANCE Autogenous MenSCs@APG may be a new stem cell-based therapy for augmenting RC healing in the clinic.
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Affiliation(s)
- Ya Song
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Ping Li
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Department of Obstetrics, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yan Xu
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
| | - Zhangyuan Lin
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhenhan Deng
- Department of Sports Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen University, Shenzhen, China
| | - Can Chen
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Department of Sports Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen University, Shenzhen, China
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Pan Y, Li Y, Dong W, Jiang B, Yu Y, Chen Y. Role of nano-hydrogels coated exosomes in bone tissue repair. Front Bioeng Biotechnol 2023; 11:1167012. [PMID: 37229488 PMCID: PMC10204869 DOI: 10.3389/fbioe.2023.1167012] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 04/26/2023] [Indexed: 05/27/2023] Open
Abstract
With the development of nanotechnology, nanomaterials are widely applied in different areas. Some nanomaterials are designed to be biocompatible and can be used in the medical field, playing an important role in disease treatment. Exosomes are nanoscale vesicles with a diameter of 30-200 nm. Studies have shown that exosomes have the effect of angiogenesis, tissue (skin, tendon, cartilage, et al.) repair and reconstruction. Nano-hydrogels are hydrogels with a diameter of 200 nm or less and can be used as the carrier to transport the exosomes into the body. Some orthopedic diseases, such as bone defects and bone infections, are difficult to handle. The emergence of nano-hydrogels coated exosomes may provide a new idea to solve these problems, improving the prognosis of patients. This review summarizes the function of nano-hydrogels coated exosomes in bone tissue repair, intending to illustrate the potential use and application of nano-hydrogels coated exosomes in bone disease.
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Affiliation(s)
- Yuqi Pan
- Department of Joint Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yige Li
- Department of Rehabilitation, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wenjun Dong
- Department of Joint Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bowei Jiang
- Department of Joint Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuhao Yu
- Department of Joint Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yunsu Chen
- Department of Joint Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Cai J, Xu J, Ye Z, Wang L, Zheng T, Zhang T, Li Y, Jiang J, Zhao J. Exosomes Derived From Kartogenin-Preconditioned Mesenchymal Stem Cells Promote Cartilage Formation and Collagen Maturation for Enthesis Regeneration in a Rat Model of Chronic Rotator Cuff Tear. Am J Sports Med 2023; 51:1267-1276. [PMID: 36917828 DOI: 10.1177/03635465231155927] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
BACKGROUND Poor tendon-to-bone healing in chronic rotator cuff tears (RCTs) is related to unsatisfactory outcomes. Exosomes derived from mesenchymal stem cells reportedly enhance rotator cuff healing. However, the difficulty in producing exosomes with a stronger effect on enthesis regeneration must be resolved. PURPOSE To study the effect of exosomes derived from kartogenin (KGN)-preconditioned human bone marrow mesenchymal stem cells (KGN-Exos) on tendon-to-bone healing in a rat model of chronic RCT. STUDY DESIGN Controlled laboratory study. METHODS Exosome-loaded sodium alginate hydrogel (SAH) was prepared. Moreover, exosomes were labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR) or 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (Dil) for in vivo tracking. Bilateral rotator cuff repair (RCR) was conducted in an established chronic RCT rat model. A total of 66 rats were randomized to control, untreated exosome (un-Exos), and KGN-Exos groups to receive local injections of pure SAH, un-Exos, or KGN-Exos SAH at the repaired site. The presence of DiR/Dil-labeled exosomes was assessed at 1 day and 1 week, and tendon-to-bone healing was evaluated histologically, immunohistochemically, and biomechanically at 4 and 8 weeks. RESULTS Both un-Exos and KGN-Exos exhibited sustained release from SAH for up to 96 hours. In vivo study revealed that un-Exos and KGN-Exos were localized to the repaired site at 1 week. Moreover, the KGN-Exos group showed a higher histological score and increased glycosaminoglycan and collagen II expression at 4 and 8 weeks. In addition, more mature and better-organized collagen fibers with higher ratios of collagen I to collagen III were observed at 8 weeks in the tendon-to-bone interface compared with those in the control and un-Exos groups. Biomechanically, the KGN-Exos group had the highest failure load (28.12 ± 2.40 N) and stiffness (28.57 ± 2.49 N/mm) among the 3 groups at 8 weeks. CONCLUSION Local injection of SAH with sustained KGN-Exos release could effectively promote cartilage formation as well as collagen maturation and organization for enthesis regeneration, contributing to enhanced biomechanical properties after RCR. CLINICAL RELEVANCE KGN-Exos injection may be used as a cell-free therapeutic option to accelerate tendon-to-bone healing in chronic RCT.
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Affiliation(s)
- Jiangyu Cai
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Junjie Xu
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zipeng Ye
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Liren Wang
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ting Zheng
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tianlun Zhang
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yufeng Li
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jia Jiang
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jinzhong Zhao
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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23
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Hu J, Liu S, Fan C. Applications of functionally-adapted hydrogels in tendon repair. Front Bioeng Biotechnol 2023; 11:1135090. [PMID: 36815891 PMCID: PMC9934866 DOI: 10.3389/fbioe.2023.1135090] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 01/23/2023] [Indexed: 02/05/2023] Open
Abstract
Despite all the efforts made in tissue engineering for tendon repair, the management of tendon injuries still poses a challenge, as current treatments are unable to restore the function of tendons following injuries. Hydrogels, due to their exceptional biocompatibility and plasticity, have been extensively applied and regarded as promising candidate biomaterials in tissue regeneration. Varieties of approaches have designed functionally-adapted hydrogels and combined hydrogels with other factors (e.g., bioactive molecules or drugs) or materials for the enhancement of tendon repair. This review first summarized the current state of knowledge on the mechanisms underlying the process of tendon healing. Afterward, we discussed novel strategies in fabricating hydrogels to overcome the issues frequently encountered during the applications in tendon repair, including poor mechanical properties and undesirable degradation. In addition, we comprehensively summarized the rational design of hydrogels for promoting stem-cell-based tendon tissue engineering via altering biophysical and biochemical factors. Finally, the role of macrophages in tendon repair and how they respond to immunomodulatory hydrogels were highlighted.
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Affiliation(s)
- Jiacheng Hu
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, China
| | - Shen Liu
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, China
| | - Cunyi Fan
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, China
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Quintero D, Perucca Orfei C, Kaplan LD, de Girolamo L, Best TM, Kouroupis D. The roles and therapeutic potentialof mesenchymal stem/stromal cells and their extracellular vesicles in tendinopathies. Front Bioeng Biotechnol 2023; 11:1040762. [PMID: 36741745 PMCID: PMC9892947 DOI: 10.3389/fbioe.2023.1040762] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 01/04/2023] [Indexed: 01/20/2023] Open
Abstract
Tendinopathies encompass a highly prevalent, multi-faceted spectrum of disorders, characterized by activity-related pain, compromised function, and propensity for an extended absence from sport and the workplace. The pathophysiology of tendinopathy continues to evolve. For decades, it has been related primarily to repetitive overload trauma but more recently, the onset of tendinopathy has been attributed to the tissue's failed attempt to heal after subclinical inflammatory and immune challenges (failed healing model). Conventional tendinopathy management produces only short-term symptomatic relief and often results in incomplete repair or healing leading to compromised tendon function. For this reason, there has been increased effort to develop therapeutics to overcome the tissue's failed healing response by targeting the cellular metaplasia and pro-inflammatory extra-cellular environment. On this basis, stem cell-based therapies have been proposed as an alternative therapeutic approach designed to modify the course of the various tendon pathologies. Mesenchymal stem/stromal cells (MSCs) are multipotent stem cells often referred to as "medicinal signaling cells" due to their immunomodulatory and anti-inflammatory properties that can produce a pro-regenerative microenvironment in pathological tendons. However, the adoption of MSCs into clinical practice has been limited by FDA regulations and perceived risk of adverse events upon infusion in vivo. The introduction of cell-free approaches, such as the extracellular vesicles of MSCs, has encouraged new perspectives for the treatment of tendinopathies, showing promising short-term results. In this article, we review the most recent advances in MSC-based and MSC-derived therapies for tendinopathies. Preclinical and clinical studies are included with comment on future directions of this rapidly developing therapeutic modality, including the importance of understanding tissue loading and its relationship to any treatment regimen.
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Affiliation(s)
- Daniel Quintero
- Department of Orthopaedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Carlotta Perucca Orfei
- Laboratorio di Biotecnologie Applicate all’Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| | - Lee D. Kaplan
- Department of Orthopaedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Laura de Girolamo
- Laboratorio di Biotecnologie Applicate all’Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| | - Thomas M. Best
- Department of Orthopaedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Dimitrios Kouroupis
- Department of Orthopaedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL, United States,Diabetes Research Institute & Cell Transplant Center, Miller School of Medicine, University of Miami, Miami, FL, United States,*Correspondence: Dimitrios Kouroupis,
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25
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Tindell RK, Busselle LP, Holloway JL. Magnetic fields enable precise spatial control over electrospun fiber alignment for fabricating complex gradient materials. J Biomed Mater Res A 2023; 111:778-789. [PMID: 36594559 DOI: 10.1002/jbm.a.37492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 12/14/2022] [Accepted: 12/16/2022] [Indexed: 01/04/2023]
Abstract
Musculoskeletal interfacial tissues consist of complex gradients in structure, cell phenotype, and biochemical signaling that are important for function. Designing tissue engineering strategies to mimic these types of gradients is an ongoing challenge. In particular, new fabrication techniques that enable precise spatial control over fiber alignment are needed to better mimic the structural gradients present in interfacial tissues, such as the tendon-bone interface. Here, we report a modular approach to spatially controlling fiber alignment using magnetically-assisted electrospinning. Electrospun fibers were highly aligned in the presence of a magnetic field and smoothly transitioned to randomly aligned fibers away from the magnetic field. Importantly, magnetically-assisted electrospinning allows for spatial control over fiber alignment at sub-millimeter resolution along the length of the fibrous scaffold similar to the native structural gradient present in many interfacial tissues. The versatility of this approach was further demonstrated using multiple electrospinning polymers and different magnet configurations to fabricate complex fiber alignment gradients. As expected, cells seeded onto gradient fibrous scaffolds were elongated and aligned on the aligned fibers and did not show a preferential alignment on the randomly aligned fibers. Overall, this fabrication approach represents an important step forward in creating gradient fibrous materials, where such materials are promising as tissue-engineered scaffolds for regenerating functional musculoskeletal interfacial tissues.
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Affiliation(s)
- Raymond Kevin Tindell
- Chemical Engineering, School of Engineering of Matter, Transport and Energy, Arizona State University, Tempe, Arizona, USA
| | - Lincoln P Busselle
- Chemical Engineering, School of Engineering of Matter, Transport and Energy, Arizona State University, Tempe, Arizona, USA
| | - Julianne L Holloway
- Chemical Engineering, School of Engineering of Matter, Transport and Energy, Arizona State University, Tempe, Arizona, USA
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Chae S, Yong U, Park W, Choi YM, Jeon IH, Kang H, Jang J, Choi HS, Cho DW. 3D cell-printing of gradient multi-tissue interfaces for rotator cuff regeneration. Bioact Mater 2023; 19:611-625. [PMID: 35600967 PMCID: PMC9109128 DOI: 10.1016/j.bioactmat.2022.05.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 05/02/2022] [Accepted: 05/02/2022] [Indexed: 12/21/2022] Open
Abstract
Owing to the prevalence of rotator cuff (RC) injuries and suboptimal healing outcome, rapid and functional regeneration of the tendon–bone interface (TBI) after RC repair continues to be a major clinical challenge. Given the essential role of the RC in shoulder movement, the engineering of biomimetic multi-tissue constructs presents an opportunity for complex TBI reconstruction after RC repair. Here, we propose a gradient cell-laden multi-tissue construct combined with compositional gradient TBI-specific bioinks via 3D cell-printing technology. In vitro studies demonstrated the capability of a gradient scaffold system in zone-specific inducibility and multi-tissue formation mimicking TBI. The regenerative performance of the gradient scaffold on RC regeneration was determined using a rat RC repair model. In particular, we adopted nondestructive, consecutive, and tissue-targeted near-infrared fluorescence imaging to visualize the direct anatomical change and the intricate RC regeneration progression in real time in vivo. Furthermore, the 3D cell-printed implant promotes effective restoration of shoulder locomotion function and accelerates TBI healing in vivo. In summary, this study identifies the therapeutic contribution of cell-printed constructs towards functional RC regeneration, demonstrating the translational potential of biomimetic gradient constructs for the clinical repair of multi-tissue interfaces.
A biomimetic cellular TBI scaffold was 3D bioprinted with dECM bioinks. A gradient multi-tissue construct was implanted for RC repair in vivo. Targeted NIR fluorescence imaging facilitated real-time monitoring of TBI regeneration. The scaffolds had therapeutic contribution on gradient TBI regeneration and functional recovery.
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Affiliation(s)
- Suhun Chae
- Department of Mechanical Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Gyeongsangbuk-do, Pohang, 37673, South Korea
- EDmicBio Inc., 111 Hoegi-ro, Dongdaemun-gu, Seoul 02445, South Korea
| | - Uijung Yong
- Department of Convergence IT Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Gyeongsangbuk-do, Pohang, 37673, South Korea
| | - Wonbin Park
- Department of Mechanical Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Gyeongsangbuk-do, Pohang, 37673, South Korea
| | - Yoo-mi Choi
- Department of Convergence IT Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Gyeongsangbuk-do, Pohang, 37673, South Korea
| | - In-Ho Jeon
- Department of Orthopaedic Surgery, Asan Medical Center, College of Medicine, University of Ulsan, 86 Asanbyeongwon-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Homan Kang
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital & Harvard Medical School, 149 13th Street, Boston, MA, 02114, USA
| | - Jinah Jang
- Department of Mechanical Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Gyeongsangbuk-do, Pohang, 37673, South Korea
- Institute for Convergence Research and Education in Advanced Technology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea
- Department of Convergence IT Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Gyeongsangbuk-do, Pohang, 37673, South Korea
- School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Gyeongsangbuk-do, Pohang, 37673, South Korea
| | - Hak Soo Choi
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital & Harvard Medical School, 149 13th Street, Boston, MA, 02114, USA
- Corresponding author.
| | - Dong-Woo Cho
- Department of Mechanical Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Gyeongsangbuk-do, Pohang, 37673, South Korea
- Institute for Convergence Research and Education in Advanced Technology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea
- Corresponding author. Department of Mechanical Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Pohang, 37673, Kyungbuk, South Korea.
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Lebaschi A, Kriscenski DE, Tamburini LM, McCarthy MB, Obopilwe E, Uyeki CL, Cote MP, Rodeo SA, Kumbar SG, Mazzocca AD. Subacromial bursa increases the failure force in a mouse model of supraspinatus detachment and repair. J Shoulder Elbow Surg 2022; 31:e519-e533. [PMID: 35690347 DOI: 10.1016/j.jse.2022.05.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 04/28/2022] [Accepted: 05/07/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND It has been shown that subacromial bursa (SAB) harbors connective tissue progenitor cells. The purpose of this study was to evaluate the effects of implantation of SAB-derived cells (SBCs) suspended in a fibrin sealant bead and implantation of SAB tissue at rotator cuff repair site on biomechanical properties of the repair in a mouse (C57Bl/6) model of supraspinatus tendon (ST) detachment and repair. METHODS Part 1: Murine SAB tissue was harvested and cultured. Viability of SBCs suspended in 10 μL of fibrin sealant beads was confirmed in vitro and in vivo. Eighty mice underwent right ST detachment and repair augmented with either fibrin sealant bead (control group) or fibrin sealant bead with 100,000 SBCs (study group) applied at the repair site. Part 2: 120 mice underwent right ST detachment and repair and were randomized equally into 4 groups: (1) a tissue group, which received a piece of freshly harvested SAB tissue; (2) a cell group, which received SBCs suspended in fibrin sealant bead; (3) a fibrin sealant group, which received plain fibrin sealant bead without cells; and (4) a control group, which received nothing at the ST repair site. An equal number of mice in each group were killed at 2 and 4 weeks. Specimens underwent biomechanical testing to evaluate failure force (part 1 and 2) and histologic analysis of the repair site (part 1 only). RESULTS Part 1: The mean failure force in the study group was significantly higher than controls at 2 and 4 weeks (3.25 ± 1.03 N vs. 2.43 ± 0.56 N, P = .01, and 4.08 ± 0.99 N vs. 3.02 ± 0.8 N, P = .004, respectively). Mean cell density of the ST at the repair site was significantly lower in the study group at 2 weeks than in controls (18,292.13 ± 1706.41 vs. 29,501.90 ± 3627.49, P = .001). Study group specimens had lower proteoglycan contents than controls, but this difference was not statistically significant. Part 2: There was no difference in failure force between cell and tissue groups at the 2- and 4-week time points (P = .994 and P = .603, respectively). There was no difference in failure force between fibrin sealant bead and control groups at the 2- and 4-week time points (P = .978 and P = .752, respectively). CONCLUSION This study shows that the application of SBCs and SAB tissue at the rotator cuff repair site increases the strength of repair in a murine model of rotator cuff detachment and repair.
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Affiliation(s)
- Amir Lebaschi
- Department of Orthopedics and Sports Medicine, University of Connecticut Health Center, Farmington, CT, USA
| | - Danielle E Kriscenski
- Department of Orthopedics and Sports Medicine, University of Connecticut Health Center, Farmington, CT, USA
| | - Lisa M Tamburini
- Department of Orthopedics and Sports Medicine, University of Connecticut Health Center, Farmington, CT, USA
| | - Mary Beth McCarthy
- Department of Orthopedics and Sports Medicine, University of Connecticut Health Center, Farmington, CT, USA
| | - Elifho Obopilwe
- Department of Orthopedics and Sports Medicine, University of Connecticut Health Center, Farmington, CT, USA
| | - Colin L Uyeki
- Department of Orthopedics and Sports Medicine, University of Connecticut Health Center, Farmington, CT, USA
| | - Mark P Cote
- Department of Orthopedics and Sports Medicine, University of Connecticut Health Center, Farmington, CT, USA
| | - Scott A Rodeo
- Sports Medicine and Shoulder Service, Hospital for Special Surgery, New York, NY, USA
| | - Sangamesh G Kumbar
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA
| | - Augustus D Mazzocca
- Division of Sports Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA, USA; Shoulder and Elbow Surgery, Harvard Medical School, Boston, MA, USA.
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Vervaecke AJ, Carbone AD, Abraham A, Bernstein Z, Laudier D, Verborgt O, Galatz LM, Huang AH. Tendon progenitor cells as biological augmentation improve functional gait and reduce scar formation after rotator cuff repair. J Shoulder Elbow Surg 2022; 31:2366-2380. [PMID: 35671924 PMCID: PMC9588545 DOI: 10.1016/j.jse.2022.05.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 05/04/2022] [Accepted: 05/07/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND High rates of structural failure are reported after rotator cuff repairs due to inability to recreate the native enthesis during healing. The development of biological augmentation methods that mitigate scar formation and regenerate the enthesis is still an unmet need. Since neonatal enthesis is capable of regeneration after injury, this study tested whether delivery of neonatal tendon progenitor cells (TPCs) into the adult injured environment can enhance functional and structural supraspinatus enthesis and tendon healing. METHODS TPCs were isolated from Ai14 Rosa26-TdTomato mouse Achilles tendons and labeled using adenovirus-Cre. Fifty-two CB57BL/6J mice underwent detachment and acute repair of the supraspinatus tendon and received either a fibrin-only or TPC-fibrin gel. Immunofluorescence analysis was carried out to determine cellularity (DAPI), fibrocartilage (SOX9), macrophages (F4/80), myofibroblasts (α-smooth muscle actin), and scar (laminin). Assays for function (gait and biomechanical testing) and structure (micro-computed tomography imaging, picrosirius red/Alcian Blue staining, type I and III collagen staining) were carried out. RESULTS Analysis of TdTomato cells after injury showed minimal retention of TPCs by day 7 and day 14, with detected cells localized near the bursa and deltoid rather than the enthesis/tendon. However, TPC delivery led to significantly increased %Sox9+ cells in the enthesis at day 7 after injury and decreased laminin intensity across almost all time points compared to fibrin-only treatment. Similarly, TPC-treated mice showed gait recovery by day 14 (paw area and stride length) and day 28 (stance time), while fibrin-treated mice failed to recover gait parameters. Despite improved gait, biomechanical testing showed no differences between groups. Structural analysis by micro-computed tomography suggests that TPC application improves cortical thickness after surgery compared to fibrin. Superior collagen alignment at the neo-enthesis was also observed in the TPC-augmented group at day 28, but no difference was detected in type I and III collagen intensity. CONCLUSION We found that neonatal TPCs improved and restored functional gait by reducing overall scar formation, improving enthesis collagen alignment, and altering bony composition response after supraspinatus tendon repair. TPCs did not appear to integrate into the healing tissue, suggesting improved healing may be due to paracrine effects at early stages. Future work will determine the factors secreted by TPCs to develop translational targets.
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Affiliation(s)
- Alexander J Vervaecke
- Department of Orthopaedics, The Mount Sinai Hospital, New York, NY, USA; Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Orthopaedic Center Antwerp, AZ Monica, Antwerp, Belgium
| | - Andrew D Carbone
- Department of Orthopaedics, The Mount Sinai Hospital, New York, NY, USA
| | - Adam Abraham
- Department of Orthopaedics, University of Michigan, Ann Arbor, Mich, USA
| | - Zachary Bernstein
- Department of Orthopaedics, The Mount Sinai Hospital, New York, NY, USA
| | - Damien Laudier
- Department of Orthopaedics, The Mount Sinai Hospital, New York, NY, USA
| | - Olivier Verborgt
- Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Orthopaedic Center Antwerp, AZ Monica, Antwerp, Belgium
| | - Leesa M Galatz
- Department of Orthopaedics, The Mount Sinai Hospital, New York, NY, USA.
| | - Alice H Huang
- Department of Orthopedic Surgery, Columbia University, New York, NY, USA.
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Shim IK, Kang MS, Lee ES, Choi JH, Lee YN, Koh KH. Decellularized Bovine Pericardial Patch Loaded With Mesenchymal Stromal Cells Enhance the Mechanical Strength and Biological Healing of Large-to-Massive Rotator Cuff Tear in a Rat Model. Arthroscopy 2022; 38:2987-3000. [PMID: 35716989 DOI: 10.1016/j.arthro.2022.06.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 03/13/2022] [Accepted: 06/03/2022] [Indexed: 02/02/2023]
Abstract
PURPOSE The purpose of this study was to determine whether the addition of decellularized bovine pericardial patch loaded with mesenchymal stromal cells enhanced bone-to-tendon healing and improved the biomechanical strength of large-to-massive rotator cuff tears in a small animal model. METHODS Adipose-derived mesenchymal stromal cells (MSCs) from rat inguinal fat were isolated, cultured, and loaded onto decellularized bovine pericardium patches. To simulate large-to-massive tears, rats were managed with free cage activity for 6 weeks after tear creation. A total of 18 rats were randomly allocated to repair-only (control), repair with pericardial patch augmentation (patch), or repair with MSC loaded pericardial patch augmentation (patch-MSC). Each group had 6 rats (one shoulder of each rat was used for histological evaluation and another for biomechanical evaluation). MSCs seeded on the pericardial patches were traced on four shoulders from 2 other rats at 4 weeks after surgery. Histological evaluation for bone-to-tendon healing and biomechanical testing was carried out at 8 weeks after repair. RESULTS MSCs tagged with a green fluorescent protein were observed in the repair site 4 weeks after the repair. One shoulder each in the control and patch groups showed complete discontinuity between the bone and tendon. One shoulder in the control group showed attenuation with only a tenuous connection. Fibrocartilage and tidemark formation at the bone-to-tendon interface (P = .002) and collagen fiber density (P = .040) and orientation (P = .003) were better in the patch-MSC group than in the control or patch group. Load-to-failure in the patch-MSC and patch groups was higher than that in the control group (P = .001 and .009, respectively). CONCLUSION Decellularized bovine pericardial patches loaded with adipose-derived and cultured mesenchymal stromal cells enhanced healing in terms of both histology and mechanical strength at 8 weeks following rotator cuff repair in a rat model. CLINICAL RELEVANCE Large-to-massive rotator tears need a strategy to prevent retear and enhance healing. The addition of decellularized bovine pericardial patch loaded with MSCs can enhance bone-to-tendon healing and improve biomechanical healing of large-to-massive rotator cuff tears following repair.
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Affiliation(s)
- In Kyong Shim
- Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Michael Seungcheol Kang
- Department of Orthopaedic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eui-Sup Lee
- Department of Orthopaedic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae Hee Choi
- Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yu Na Lee
- Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyoung Hwan Koh
- Department of Orthopaedic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
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Chen C, Shi Q, Li M, Chen Y, Zhang T, Xu Y, Liao Y, Ding S, Wang Z, Li X, Zhao C, Sun L, Hu J, Lu H. Engineering an enthesis-like graft for rotator cuff repair: An approach to fabricate highly biomimetic scaffold capable of zone-specifically releasing stem cell differentiation inducers. Bioact Mater 2022; 16:451-471. [PMID: 35386315 PMCID: PMC8965727 DOI: 10.1016/j.bioactmat.2021.12.021] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 11/29/2021] [Accepted: 12/19/2021] [Indexed: 02/09/2023] Open
Abstract
Rotator cuff (RC) attaches to humerus across a triphasic yet continuous tissue zones (bone-fibrocartilage-tendon), termed "enthesis". Regrettably, rapid and functional enthesis regeneration is challenging after RC tear. The existing grafts bioengineered for RC repair are insufficient, as they were engineered by a scaffold that did not mimic normal enthesis in morphology, composition, and tensile property, meanwhile cannot simultaneously stimulate the formation of bone-fibrocartilage-tendon tissues. Herein, an optimized decellularization approach based on a vacuum aspiration device (VAD) was developed to fabricate a book-shaped decellularized enthesis matrix (O-BDEM). Then, three recombinant growth factors (CBP-GFs) capable of binding collagen were synthesized by fusing a collagen-binding peptide (CBP) into the N-terminal of BMP-2, TGF-β3, or GDF-7, and zone-specifically tethered to the collagen of O-BDEM to fabricate a novel scaffold (CBP-GFs/O-BDEM) satisfying the above-mentioned requirements. After ensuring the low immunogenicity of CBP-GFs/O-BDEM by a novel single-cell mass cytometry in a mouse model, we interleaved urine-derived stem cell-sheets into this CBP-GFs/O-BDEM to bioengineer an enthesis-like graft. Its high-performance on regenerating enthesis was determined in a canine model. These findings indicate this CBP-GFs/O-BDEM may be an excellent scaffold for constructing enthesis-like graft to patch large/massive RC tears, and provide breakthroughs in fabricating graded interfacial tissue.
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Affiliation(s)
- Can Chen
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Qiang Shi
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Muzhi Li
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Rehabilitation, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China
| | - Yang Chen
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Tao Zhang
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Yan Xu
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Yunjie Liao
- Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Shulin Ding
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Zhanwen Wang
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Xing Li
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Chunfeng Zhao
- Division of Orthopedic Research and Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, 55905, United States
| | - Lunquan Sun
- Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Jianzhong Hu
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Corresponding author. Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, 410008, Hunan, China.
| | - Hongbin Lu
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Corresponding author. Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, 410008, Hunan, China.
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Ferracini R, Artiaco S, Daghino W, Falco M, Gallo A, Garibaldi R, Tiraboschi E, Guidotti C, Bistolfi A. Microfragmented Adipose Tissue (M-FATS) for Improved Healing of Surgically Repaired Achilles Tendon Tears: A Preliminary Study. Foot Ankle Spec 2022; 15:472-478. [PMID: 33241717 DOI: 10.1177/1938640020974557] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
INTRODUCTION Tendon healing is a complicated process that results in inferior structural and functional properties when compared with healthy tendon; the purpose of this study was to assess the effects of the adjunct of microfragmented adipose tissue (M-FATS) after the suture of a series of Achilles tendons. METHODS After complete Achilles tendon tear, 8 patients underwent open suture repair in conjunction with perilesional application of a preparation of M-FATS rich in mesenchymal stem cells. Results were compared with a similar group of patients treated with conventional open suture. Outcomes were evaluated based on range of motion, functional recovery, and complications according to the American Orthopedic Foot and Ankle Society (AOFAS) score and Foot and Ankle Disability Index (FADI). Achilles tendons were examined by ultrasound (US) at 3 months. RESULTS The AOFAS and FADI scores showed no differences between the 2 groups. US evaluation showed quicker tendon remodeling in the M-FATS group. Adverse events were not documented for both procedures. CONCLUSIONS The combined application of derived M-FATS for tendon rupture is safe and presents new possibilities for enhanced healing. LEVELS OF EVIDENCE Level IIIb: Case control study.
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Affiliation(s)
- Riccardo Ferracini
- Orthopaedic Unit, Koelliker Hospital, Turin, Italy.,Orthopaedic Clinic, University of Genova, Italy
| | - Stefano Artiaco
- Department of Orthopaedics, Traumatology and Rehabilitation, Hospital Città della Salute e della Scienza, Turin, Italy
| | - Walter Daghino
- Department of Orthopaedics, Traumatology and Rehabilitation, Hospital Città della Salute e della Scienza, Turin, Italy
| | - Mara Falco
- Radiodiagnostic Cellini Humanitas, Turin, Italy
| | - Alessandra Gallo
- Diagnostic Imaging and Radiotherapy, Koelliker Hospital, Turin, Italy
| | | | | | - Claudio Guidotti
- Department of Orthopaedics, Traumatology and Rehabilitation, Hospital Città della Salute e della Scienza, Turin, Italy
| | - Alessandro Bistolfi
- Department of Orthopaedics, Traumatology and Rehabilitation, Hospital Città della Salute e della Scienza, Turin, Italy
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Wu Y, Shao Y, Xie D, Pan J, Chen H, Yao J, Liang J, Ke H, Cai D, Zeng C. Effect of secretory leucocyte protease inhibitor on early tendon-to-bone healing after anterior cruciate ligament reconstruction in a rat model. Bone Joint Res 2022; 11:503-512. [PMID: 35866455 PMCID: PMC9350708 DOI: 10.1302/2046-3758.117.bjr-2021-0358.r2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
AIMS To verify whether secretory leucocyte protease inhibitor (SLPI) can promote early tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction. METHODS In vitro: the mobility of the rat bone mesenchymal stem cells (BMSCs) treated with SLPI was evaluated by scratch assay. Then the expression levels of osteogenic differentiation-related genes were analyzed by real-time quantitative PCR (qPCR) to determine the osteogenic effect of SLPI on BMSCs. In vivo: a rat model of ACL reconstruction was used to verify the effect of SLPI on tendon-to-bone healing. All the animals of the SLPI group and the negative control (NC) group were euthanized for histological evaluation, micro-CT scanning, and biomechanical testing. RESULTS SLPI improved the migration ability of BMSCs and upregulated the expression of genes related to osteogenic differentiation of BMSCs in vitro. In vivo, the SLPI group had higher histological scores at the tendon-bone interface by histological evaluation. Micro-CT showed more new bone formation and bone ingrowth around the grafted tendon in the SLPI group. Evaluation of the healing strength of the tendon-bone connection showed that the SLPI group had a higher maximum failure force and stiffness. CONCLUSION SLPI can effectively promote early tendon-to-bone healing after ACL reconstruction via enhancing the migration and osteogenic differentiation of BMSCs. Cite this article: Bone Joint Res 2022;11(7):503-512.
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Affiliation(s)
- Yongmao Wu
- Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.,The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China.,Department of Orthopedics, Fourth Affiliated Hospital of Guangxi Medical University/ Liuzhou Workers' Hospital, Liuzhou, China
| | - Yan Shao
- Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.,The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China
| | - Denghui Xie
- Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.,The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China
| | - Jianying Pan
- Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.,The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China
| | - Huabin Chen
- Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.,The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Juncheng Yao
- Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.,The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Jiarong Liang
- Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.,The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Haolin Ke
- Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.,The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Daozhang Cai
- Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.,The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China
| | - Chun Zeng
- Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.,The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China
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Muthu S, Jeyaraman N, Patel K, Chellamuthu G, Viswanathan VK, Jeyaraman M, Khanna M. Evidence analysis on the utilization of platelet-rich plasma as an adjuvant in the repair of rotator cuff tears. World J Meta-Anal 2022; 10:143-161. [DOI: 10.13105/wjma.v10.i3.143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 03/23/2022] [Accepted: 06/26/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Platelet-rich plasma has been gaining popularity as an agent for biological augmentation either as the sole treatment modality or as an adjunct to surgical repair. There is substantial discrepancy in the results of the published meta-analyses; and the true efficacy and role of using autologous platelet-rich plasma (PRP) at the time of rotator cuff repair is still ambiguous.
AIM To performed this systematic overview on the overlapping meta-analyses that analyzed autologous PRP as an adjuvant in the repair of rotator cuff tears and identify the studies which provide the current best evidence on this subject and generate recommendations for the same.
METHODS We conducted independent and duplicate electronic database searches in PubMed, Web of Science, Scopus, Embase, Cochrane Database of Systematic Reviews, Reference Citation Analysis and the Database of Abstracts of Reviews of Effects on September 8, 2021 to identify meta-analyses that analyzed the efficacy of PRP as an adjuvant in the repair of rotator cuff tears. Methodological quality assessment was made using Oxford Levels of Evidence, AMSTAR scoring and AMSTAR 2 grades. We then utilized the Jadad decision algorithm to identify the study with the highest quality to represent the current best evidence to generate the recommendation.
RESULTS Twenty meta-analyses fulfilling the eligibility criteria were included. The AMSTAR scores of the included studies varied from 6-10 (mean: 7.9). All the included studies had critically low reliability in their summary of results due to their methodological flaws according to AMSTAR 2 grades. Significant heterogeneity was observed in the reporting of VAS, function outcome scores (long-term UCLA score, ASES score, SST score), operative time and long-term re-tear rates. Recent meta-analyses are more supportive of the role of intra-operative administration of PRPs at the bone-tendon interface in improving the overall healing and re-tear rates, functional outcome and pain. The initial size of the tear and type of repair performed do not seem to affect the benefit of PRPs. Among the different preparations used, leucocyte poor (LP)-PRP possibly offers the greatest benefit as a biological augment in these situations.
CONCLUSION Based on this systematic overview, we give a level II recommendation that intra-operative use of PRPs at the bone-tendon interface can augment the healing rate, reduce re-tears, enhance functional outcome and mitigate pain in patients undergoing arthroscopic rotator cuff repair. LP-PRP possibly offers the greatest benefit in terms of healing rates, as compared with other platelet preparations.
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Affiliation(s)
- Sathish Muthu
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul 624001, Tamil Nadu, India
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201306, Uttar Pradesh, India
- Research Associate, Indian Stem Cell Study GroupAssociation, Lucknow 226010, Uttar Pradesh, India
- Research Associate, Orthopaedic Research Group, Coimbatore 641001, Tamil Nadu, India
| | - Naveen Jeyaraman
- Research Associate, Indian Stem Cell Study GroupAssociation, Lucknow 226010, Uttar Pradesh, India
- Research Associate, Orthopaedic Research Group, Coimbatore 641001, Tamil Nadu, India
- Fellow in Orthopaedic Rheumatology, Dr Ram Manohar Lohiya National Law University, Lucknow 226010, Uttar Pradesh, India
- Fellow in Joint Replacement, Atlas Hospitals (The Tamil Nadu Dr MGR Medical University), Tiruchirappalli 620002, Tamil Nadu, India
| | - Keval Patel
- Research Associate, Indian Stem Cell Study GroupAssociation, Lucknow 226010, Uttar Pradesh, India
- Fellow in Orthopaedic Rheumatology, Dr Ram Manohar Lohiya National Law University, Lucknow 226010, Uttar Pradesh, India
| | - Girinivasan Chellamuthu
- Research Associate, Indian Stem Cell Study GroupAssociation, Lucknow 226010, Uttar Pradesh, India
- Research Associate, Orthopaedic Research Group, Coimbatore 641001, Tamil Nadu, India
- Fellow in Arthroscopy, Ortho-One Orthopaedic Speciality Centre (The Tamil Nadu Dr MGR Medical University), Coimbatore 641005, Tamil Nadu, India
| | - Vibhu Krishnan Viswanathan
- Department of Orthopaedics and Spine Surgery, Ganga Medical Centre and Hospitals, Coimbatore 641043, Tamil Nadu, India
| | - Madhan Jeyaraman
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201306, Uttar Pradesh, India
- Research Associate, Indian Stem Cell Study GroupAssociation, Lucknow 226010, Uttar Pradesh, India
- Research Associate, Orthopaedic Research Group, Coimbatore 641001, Tamil Nadu, India
- Department of Orthopaedics, Faculty of Medicine, Sri Lalithambigai Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600095, Tamil Nadu, India
- South Texas Orthopaedic Research Institute, Laredo, TX 78045, United States
| | - Manish Khanna
- Research Associate, Indian Stem Cell Study GroupAssociation, Lucknow 226010, Uttar Pradesh, India
- Research Associate, Orthopaedic Research Group, Coimbatore 641001, Tamil Nadu, India
- Department of Orthopaedics, Autonomous State Medical College, Ayodhya 224135, Uttar Pradesh, India
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Zuo R, Liu J, Zhang Y, Zhang H, Li J, Wu J, Ji Y, Mao S, Li C, Zhou Y, Wu Y, Cai D, Sun Y, Zhang C. In situ regeneration of bone-to-tendon structures: Comparisons between costal-cartilage derived stem cells and BMSCs in the rat model. Acta Biomater 2022; 145:62-76. [PMID: 35381396 DOI: 10.1016/j.actbio.2022.03.056] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 03/25/2022] [Accepted: 03/30/2022] [Indexed: 11/01/2022]
Abstract
Bone-tendon interface (BTI), also called enthesis, is composed of the bone, fibrocartilage, and tendon/ligament with gradual structural characteristics. The unique gradient structure is particularly important for mechanical stress transfer between bone and soft tissues. However, BTI injuries result in fibrous scar repairs and high incidences of re-rupture, which is attributed to the lack of local stem cells with tenogenic and osteogenic potentials. In the rat model, we identified unique stem cells from costal cartilage (CDSCs) with a high in situ regeneration potential of BTI structures. Compared to bone-marrow mesenchymal stem cells (BMSCs), CDSCs exhibit higher self-renewal capacities, better adaptability to low-oxygen and low-nutrient post-transplantation environments, as well as strong bi-potent differentiation abilities of osteogenesis and tenogenesis. After transplantation, CDSCs can survive, proliferate, and in situ gradually regenerate BTI structures. Therefore, CDSCs have a great potential for tissue engineering regeneration in BTI injuries, and have future clinical application prospects. STATEMENT OF SIGNIFICANCE: Tissue engineering is a promising technique for bone-to-tendon interface (BTI) regeneration after injury, but it is still a long way from clinical application. One of the major reasons is the lack of suitable seed cells. This study found an ideal source of seed cells derived from costal cartilages (CDSCs). Compared to the traditional seed cell BMSCs, CDSCs have higher proliferation ability, strong chondrogenic and tenogenic differentiation potential, and better adaptability to low-oxygen and low nutrient conditions. CDSCs were able to survive, proliferate, and regenerate BTI structures in situ, in contrast to BMSCs. CDSCs transplantation showed strong BTI structures regeneration potential both histologically and biomechanically, making it a suitable seed cell for the tissue engineering regeneration of BTI.
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Wang HN, Rong X, Yang LM, Hua WZ, Ni GX. Advances in Stem Cell Therapies for Rotator Cuff Injuries. Front Bioeng Biotechnol 2022; 10:866195. [PMID: 35694228 PMCID: PMC9174670 DOI: 10.3389/fbioe.2022.866195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Accepted: 04/25/2022] [Indexed: 11/13/2022] Open
Abstract
Rotator cuff injury is a common upper extremity musculoskeletal disease that may lead to persistent pain and functional impairment. Despite the clinical outcomes of the surgical procedures being satisfactory, the repair of the rotator cuff remains problematic, such as through failure of healing, adhesion formation, and fatty infiltration. Stem cells have high proliferation, strong paracrine action, and multiple differentiation potential, which promote tendon remodeling and fibrocartilage formation and increase biomechanical strength. Additionally, stem cell-derived extracellular vesicles (EVs) can increase collagen synthesis and inhibit inflammation and adhesion formation by carrying regulatory proteins and microRNAs. Therefore, stem cell-based therapy is a promising therapeutic strategy that has great potential for rotator cuff healing. In this review, we summarize the advances of stem cells and stem cell-derived EVs in rotator cuff repair and highlight the underlying mechanism of stem cells and stem cell-derived EVs and biomaterial delivery systems. Future studies need to explore stem cell therapy in combination with cellular factors, gene therapy, and novel biomaterial delivery systems.
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Affiliation(s)
- Hao-Nan Wang
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - Xiao Rong
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, China
| | - Lu-Ming Yang
- Musculoskeletal Sonography and Occupational Performance Lab, Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, CA, United States
| | - Wei-Zhong Hua
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - Guo-Xin Ni
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing, China
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Kenmoku T, Nakai D, Nagura N, Onuma K, Sukegawa K, Tazawa R, Otake Y, Takahira N, Takaso M. Tenodesis with bone marrow venting under local anesthesia for recalcitrant lateral epicondylitis: Results of 2 years of follow-up. JSES Int 2022; 6:696-703. [PMID: 35813152 PMCID: PMC9264004 DOI: 10.1016/j.jseint.2022.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Hypothesis We hypothesized that the treatment of recalcitrant lateral epicondylitis requires accurate identification of the painful area to promote remodeling of the degenerated extensor insertion and to stabilize the tendon origin during tendon healing. Thus, we performed tenodesis with bone marrow venting under local anesthesia for recalcitrant lateral epicondylitis. Methods Twenty patients (21 elbows) were treated with bone marrow venting at the painful area of the lateral epicondyle of the elbow and tenodesis using 2 soft anchors lateral to the capitellum (immediately distal to the painful area) and were followed up for ≥2 years. Patients were assessed using the numerical rating scale for pain and the Quick Disabilities of the Arm, Shoulder, and Hand questionnaire, and objective evaluation included active range of motion. Results The mean preoperative and postoperative pain scores were 7.5 and 0.5, respectively, indicating significant pain relief (P < .001). The mean preoperative and postoperative Quick Disabilities of the Arm, Shoulder, and Hand questionnaire scores were 44.2 and 1.0, respectively (P < .001). Two elbows had a slightly positive Thomsen test at the final visit. No recurrence of intra-articular symptoms induced by synovial fringe impingement was observed. Patients experienced more pain at the bone-tendon junction of extensors than at the tendon parenchyma. Conclusion Tenodesis with bone marrow venting under local anesthesia was effective for subjective patient satisfaction and positive clinical outcomes at ≥2 years of follow-up in patients with recalcitrant lateral epicondylitis. Intra-articular symptoms can be improved by stabilization of the lateral soft tissue without treatment for intra-articular lesions.
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Washington KS, Shemshaki NS, Laurencin CT. The Role of Nanomaterials and Biological Agents on Rotator Cuff Regeneration. REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE 2022; 7:440-449. [PMID: 35005215 DOI: 10.1007/s40883-020-00171-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The rotator cuff is a musculotendon unit responsible for movement in the shoulder. Rotator cuff tears represent a significant number of musculoskeletal injuries in the adult population. In addition, there is a high incidence of retear rates due to various complications within the complex anatomical structure and the lack of proper healing. Current clinical strategies for rotator cuff augmentation include surgical intervention with autograft tissue grafts and beneficial impacts have been shown, but challenges still exist because of limited supply. For decades, nanomaterials have been engineered for the repair of various tissue and organ systems. This review article provides a thorough summary of the role nanomaterials, stem cells and biological agents have played in rotator cuff repair to date and offers input on next generation approaches for regenerating this tissue.
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Affiliation(s)
- Kenyatta S Washington
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030, USA
| | - Nikoo Saveh Shemshaki
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030, USA.,Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA.,Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA.,Department of Orthopedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA
| | - Cato T Laurencin
- Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030, USA.,Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA.,Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA.,Department of Orthopedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA.,Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USA.,Department of Chemical & Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA.,Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health, Farmington, CT 06030, USA
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38
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Chen HS, Yau YC, Ko PT, Yen BLJ, Ho CT, Hung SC. Mesenchymal Stem Cells From a Hypoxic Culture Can Improve Rotator Cuff Tear Repair. Cell Transplant 2022; 31:9636897221089633. [PMID: 35438571 PMCID: PMC9021471 DOI: 10.1177/09636897221089633] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
A rotator cuff tear is an age-related common cause of pain and disability. Studies including our previously published ones have demonstrated that mesenchymal stem cells cultured under hypoxic conditions [hypoxic multipotent stromal cells (MSCs)] facilitate the retention of transplanted cells and promote wound healing. However, there are very few, if any, reports targeting the punctured supraspinatus tendons to create more or equally serous wounds as age-related tears of rotator cuff. It remains to be determined whether transplantation of bone-marrow-derived hypoxic MSCs into the punctured supraspinatus tendon improves tendon repair and, when combined with ultrasound-guided delivery, could be used for future clinical applications. In this study, we used a total of 33 Sprague-Dawley rats in different groups for normal no-punched control, hypoxic MSC treatment, nontreated vehicle control, and MSC preparation, and then evaluated treatment outcomes by biomechanical testing and histological analysis. We found that the ultimate failure load of the hypoxic MSC-treated group was close to that of the normal tendon and significantly greater than that of the nontreated vehicle control group. In vivo tracking of cells labeled with superparamagnetic iron oxide (SPIO) nanoparticles revealed an enhanced retention of transplanted cells at the tear site. Our study demonstrates that hypoxic MSCs improve rotator cuff tear repair in a rat model.
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Affiliation(s)
- Hsin-Shui Chen
- PhD Program for Aging, College of Medicine, China Medical University, Taichung.,Department of Physical Medicine & Rehabilitation, National Taiwan University Hospital Yunlin Branch, Yunlin
| | - Yun-Chain Yau
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei
| | - Pin-Tsou Ko
- Department of Pathology, An-Nan Hospital, China Medical University, Tainan
| | - Betty Lin-Ju Yen
- Institute of Cellular & System Medicine, Regenerative Medicine Research Group, National Health Research Institutes, Zhunan
| | - Chun-Te Ho
- Institute of New Drug Development, China Medical University, Taichung.,Integrative Stem Cell Center, China Medical University Hospital, Taichung
| | - Shih-Chieh Hung
- Institute of New Drug Development, China Medical University, Taichung.,Integrative Stem Cell Center, China Medical University Hospital, Taichung
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Day Hazra RO, Ernat JJ, Rakowski DR, Boykin RE, Millett PJ. The Evolution of Arthroscopic Rotator Cuff Repair. Orthop J Sports Med 2021; 9:23259671211050899. [PMID: 34901288 PMCID: PMC8652190 DOI: 10.1177/23259671211050899] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 07/19/2021] [Indexed: 01/08/2023] Open
Abstract
Over the past 30 years, arthroscopic rotator cuff repair (ARCR) has evolved to become the gold standard in treating rotator cuff pathology. As procedural concepts of ARCR continue to improve, it is also continually compared with the open rotator cuff repair as the historical standard of care. This review highlights the evolution of ARCR, including a historical perspective; the anatomic, clinical, and surgical implications of the development of an arthroscopic approach; how arthroscopy improved some of the problems of the open approach; adaptations in techniques and technologies associated with ARCR; future perspectives in orthobiologics as they pertain to ARCR; and lastly, the clinical improvements, or lack of improvements, with all of these adaptations.
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Affiliation(s)
- Rony-Orijit Day Hazra
- Steadman Philippon Research Institute, Vail, Colorado, USA.,The Steadman Clinic, Vail, Colorado, USA
| | - Justin J Ernat
- Steadman Philippon Research Institute, Vail, Colorado, USA.,University of Utah Health, Salt Lake City, Utah, USA
| | | | - Robert E Boykin
- Steadman Philippon Research Institute, Vail, Colorado, USA.,EmergeOrtho, Asheville, North Carolina, USA
| | - Peter J Millett
- Steadman Philippon Research Institute, Vail, Colorado, USA.,The Steadman Clinic, Vail, Colorado, USA
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40
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Significant Improvement in Shoulder Function and Pain in Patients Following Biologic Augmentation of Revision Arthroscopic Rotator Cuff Repair Using an Autologous Fibrin Scaffold and Bone Marrow Aspirate Derived From the Proximal Humerus. Arthrosc Sports Med Rehabil 2021; 3:e1819-e1825. [PMID: 34977636 PMCID: PMC8689277 DOI: 10.1016/j.asmr.2021.08.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Accepted: 08/18/2021] [Indexed: 12/30/2022] Open
Abstract
Purpose To clinically evaluate patients who underwent a biologic augmentation technique in revision arthroscopic rotator cuff repair using an autologous fibrin scaffold and concentrated stem cells isolated from bone marrow aspirate (BMA) obtained from the proximal humerus. Methods This is a retrospective review of prospectively collected data from patients who underwent biologic augmentation of revision arthroscopic rotator cuff repair using an autologous fibrin scaffold and BMA obtained from the proximal humerus between 2014 and 2015. Minimum follow-up was 12 months. Outcome measures were collected preoperatively and postoperatively including range of motion as well as American Shoulder and Elbow Surgeons Shoulder Form, Simple Shoulder Test, single assessment numeric evaluation, and visual analog score. In addition, BMA samples of each patient were assessed for the number of nucleated cells and colony-forming units. Regression analysis was performed to investigate whether the number of nucleated cells and colony-forming units had an influence on outcome and failure. Results Ten patients who underwent biologic augmentation of revision arthroscopic rotator cuff repair using an autologous fibrin scaffold and concentrated BMA obtained from the proximal humerus between 2014 and 2015 were included. The mean follow-up time was 30.7 (range: 12-49) months. Four patients were revised at final follow-up. Postoperative clinical scores improved significantly: American Shoulder and Elbow Surgeons (28.1 ± 5.4 to 60.9 ± 9.0; P < .01), single assessment numeric evaluation (6.6 ± 2.3 to 65.1 ± 10.9; P < .01), visual analog scale (7.2 ± 0.9 to 3.1 ± 0.9; P < .01), and Simple Shoulder Test (1.6 ± 0.5 to 10.3 ± 5.7; P < .01). Postoperative range of motion increased significantly with regard to flexion (97.0 ± 13.6 to 151.0 ± 12.2; P < .01) and abduction (88.0 ± 14.0 to 134.0 ± 15.1; P = .038) but not with external rotation (38.0 ± 5.7 to 50.5 ± 6.5; P = .16). Less pain was correlated to an increased number of nucleated cells (P = .026); however, there was no correlation between failure rate and number of nucleated cells (P = .430). Conclusions Patients who underwent biologic augmentation of revision arthroscopic rotator cuff repair using an autologous fibrin scaffold and concentrated BMA demonstrated a significant improvement in shoulder function along with reduction of pain. However, the overall revision rate for this procedure was 40%. Level of Evidence Level IV, therapeutic case series.
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Anderson LE, Pearson JJ, Brimeyer AL, Temenoff JS. Injection of Micronized Human Amnion/Chorion Membrane Results in Increased Early Supraspinatus Muscle Regeneration in a Chronic Model of Rotator Cuff Tear. Ann Biomed Eng 2021; 49:3698-3710. [PMID: 34766224 DOI: 10.1007/s10439-021-02880-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 10/18/2021] [Indexed: 01/08/2023]
Abstract
Surgical repair of severe rotator cuff tear often results in retear due to unaddressed muscle degeneration. The objective of this study was to test the regenerative potential of micronized dehydrated Human Amnion/Chorion Membrane (dHACM), in a clinically relevant delayed reattachment model of rotator cuff repair. Micronized dHACM was injected into rat supraspinatus muscle during tendon re-attachment surgery, three weeks after original tendon injury. One week after material injection, inflammatory and mesenchymal stem cell infiltration into supraspinatus muscles was assessed via flow cytometry. Histological methods were utilized to assess structural and regenerative changes in muscle one and three weeks after material injection. Micronized dHACM injection resulted in increased M1-like macrophages (17.1 [Formula: see text] fold change over contralateral controls) and regenerating muscle fibers (4.3% vs 1.7% in saline treated muscles) one week after injection compared to saline treated muscles. Tendon reattachment itself exhibited intrinsic healing in this model, demonstrated by a general return of muscle weight and reduced fibrosis. Our results indicate that injection of micronized dHACM may initiate an inflammatory response in degenerated muscle that promotes early muscle regeneration, and that our animal model may be a suitable platform for studying treatments in muscle at early timepoints, before intrinsic healing occurs.
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Affiliation(s)
- Leah E Anderson
- Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech, Emory University, 315 Ferst Dr., Atlanta, GA, 30332, USA
| | - Joseph J Pearson
- Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech, Emory University, 315 Ferst Dr., Atlanta, GA, 30332, USA
| | - Alexandra L Brimeyer
- Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech, Emory University, 315 Ferst Dr., Atlanta, GA, 30332, USA
| | - Johnna S Temenoff
- Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech, Emory University, 315 Ferst Dr., Atlanta, GA, 30332, USA.
- Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
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He S, Qin T. [Research progress of interfacial tissue engineering in rotator cuff repair]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2021; 35:1341-1351. [PMID: 34651491 DOI: 10.7507/1002-1892.202104064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Objective To summarize the research progress of interfacial tissue engineering in rotator cuff repair. Methods The recent literature at home and abroad concerning interfacial tissue engineering in rotator cuff repair was analysed and summarized. Results Interfacial tissue engineering is to reconstruct complex and hierarchical interfacial tissues through a variety of methods to repair or regenerate damaged joints of different tissues. Interfacial tissue engineering in rotator cuff repair mainly includes seed cells, growth factors, biomaterials, oxygen concentration, and mechanical stimulation. Conclusion The best strategy for rotator cuff healing and regeneration requires not only the use of biomaterials with gradient changes, but also the combination of seed cells, growth factors, and specific culture conditions (such as oxygen concentration and mechanical stimulation). However, the clinical transformation of the relevant treatment is still a very slow process.
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Affiliation(s)
- Shukun He
- Laboratory of Stem Cells and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Tingwu Qin
- Laboratory of Stem Cells and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
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Condron NB, Kester BS, Tokish JM, Zumstein MA, Gobezie R, Scheibel M, Cole BJ. Nonoperative and Operative Soft-Tissue, Cartilage, and Bony Regeneration and Orthopaedic Biologics of the Shoulder: An Orthoregeneration Network (ON) Foundation Review. Arthroscopy 2021; 37:3200-3218. [PMID: 34293441 DOI: 10.1016/j.arthro.2021.06.033] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 06/16/2021] [Indexed: 02/02/2023]
Abstract
Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electro-magnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the shoulder including the rotator cuff tendons, glenohumeral articular cartilage, glenoid labrum, the joint capsule, and bone. Promising and established treatment modalities include hyaluronic acid (HA); platelet-rich plasma (PRP) and platelet rich concentrates (PRC); bone marrow aspirate (BMA) comprising mesenchymal stromal cells (MSCs alternatively termed medicinal signaling cells and frequently, misleadingly labelled "mesenchymal stem cells"); MSC harvested from adipose, umbilical, or placental sources; factors including vascular endothelial growth factors (VEGF), basic fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGFβ), bone morphogenic protein (BMP), and matrix metalloproteinases (MMPs); prolotherapy; pulsed electromagnetic field therapy; microfracture and other marrow-stimulation techniques; biologic resurfacing using acellular dermal allografts, allograft Achilles tendons, allograft lateral menisci, fascia lata autografts, and porcine xenografts; osteochondral autograft or allograft); and autologous chondrocyte implantation (ACI). Studies involving hyaluronic acid, platelet rich plasma, and medicinal signaling cells of various origin tissues have shown mixed results to-date as isolated treatments and as surgical adjuncts. Despite varied results thus far, there is great potential for improved efficacy with refinement of current techniques and translation of burgeoning preclinical work. LEVEL OF EVIDENCE: Level V, expert opinion.
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Affiliation(s)
| | | | | | - Matthias A Zumstein
- Orthopaedics Sonnenhof, Bern, and Department of Orthopaedics and Traumatology, University of Bern, Inselspital, Bern, Switzerland
| | | | - Markus Scheibel
- Department for Shoulder and Elbow Surgery, Schulthess Clinic, Zurich, Switzerland; Center for Musculoskeletal Surgery, Charité-Universitaetsmedizin, Berlin, Germany
| | - Brian J Cole
- Midwest Orthopaedics at Rush, Chicago, Illinois, U.S.A..
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Ryan JM, Imbergamo C, Sudah S, Kirchner G, Greenberg P, Monica J, Gatt C. Platelet-Rich Product Supplementation in Rotator Cuff Repair Reduces Retear Rates and Improves Clinical Outcomes: A Meta-analysis of Randomized Controlled Trials. Arthroscopy 2021; 37:2608-2624. [PMID: 33744318 PMCID: PMC8349828 DOI: 10.1016/j.arthro.2021.03.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 03/01/2021] [Accepted: 03/05/2021] [Indexed: 02/02/2023]
Abstract
PURPOSE The purpose of this study was to conduct a comprehensive systematic review and meta-analysis to investigate the clinical and imaging outcomes of all 4 types of platelet-rich therapies (pure platelet-rich plasma [P-PRP], leukocyte and platelet-rich plasma, pure platelet-rich fibrin, and leukocyte and platelet-rich fibrin) in rotator cuff repairs. METHODS A systematic literature search was performed to identify rotator cuff tears comparing any of the 4 types of platelet-rich products (PRP) to a control in rotator cuff repair. Data extracted from the studies included retear rates diagnosed with imaging studies, as well as outcome scores such as Constant, American Shoulder and Elbow Surgeons (ASES), University of California Los Angeles (UCLA), Simple Shoulder Test (SST), and visual analog scale (VAS). Meta-analyses compared postoperative outcome scores and retear rates between the control and study groups. RESULTS Seventeen studies were included in the meta-analysis. When pooling data from all studies, retear rate for the treatment group was 19.3%, compared to 25.4% for the control group (odds ratio [OR] 0.59, P = .0037). When stratified based on PRP type, only P-PRP resulted in a significant reduction in retear rate (OR 0.26, P = .0005). Overall, treatment with PRP significantly improved Constant scores when compared to controls (mean difference [MD] 2.41, P =.0027), as well as VAS scores (MD -0.12, P = .0014), and SST scores (MD 0.41, P = .0126). There was no significant difference in ASES scores (MD 0.37, P = .7762) or UCLA scores (MD 0.76, P =0.2447) between treatment and controls when pooling data from all studies. CONCLUSIONS This analysis demonstrates significant reductions in retear rates when rotator cuff repair is augmented with PRP. P-PRP appears to be the most effective formulation, resulting in significantly improved retear rates and clinical outcome scores when compared with controls.
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Affiliation(s)
- James M Ryan
- Rutgers Robert Wood Johnson Medical School, New Brunswick,
NJ
| | - Casey Imbergamo
- Rutgers Robert Wood Johnson Medical School, New Brunswick,
NJ
| | | | | | | | - James Monica
- Rutgers Robert Wood Johnson Medical School, New Brunswick,
NJ
| | - Charles Gatt
- Rutgers Robert Wood Johnson Medical School, New Brunswick,
NJ
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45
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Xu Y, Zhang WX, Wang LN, Ming YQ, Li YL, Ni GX. Stem cell therapies in tendon-bone healing. World J Stem Cells 2021; 13:753-775. [PMID: 34367476 PMCID: PMC8316867 DOI: 10.4252/wjsc.v13.i7.753] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 05/08/2021] [Accepted: 06/23/2021] [Indexed: 02/06/2023] Open
Abstract
Tendon-bone insertion injuries such as rotator cuff and anterior cruciate ligament injuries are currently highly common and severe. The key method of treating this kind of injury is the reconstruction operation. The success of this reconstructive process depends on the ability of the graft to incorporate into the bone. Recently, there has been substantial discussion about how to enhance the integration of tendon and bone through biological methods. Stem cells like bone marrow mesenchymal stem cells (MSCs), tendon stem/progenitor cells, synovium-derived MSCs, adipose-derived stem cells, or periosteum-derived periosteal stem cells can self-regenerate and potentially differentiate into different cell types, which have been widely used in tissue repair and regeneration. Thus, we concentrate in this review on the current circumstances of tendon-bone healing using stem cell therapy.
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Affiliation(s)
- Yue Xu
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Wan-Xia Zhang
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Li-Na Wang
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Yue-Qing Ming
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Yu-Lin Li
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Guo-Xin Ni
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China.
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Campbell TM, Gao L, Laneuville O, Louati H, Uhthoff HK, Trudel G. Rotator cuff anchor repair: Histological changes associated with the recovering mechanical properties in a rabbit model. J Tissue Eng Regen Med 2021; 15:567-576. [PMID: 33817988 DOI: 10.1002/term.3195] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Accepted: 03/24/2021] [Indexed: 01/08/2023]
Abstract
Rotator cuff anchor repair is an increasingly common surgical procedure but the failure rate remains high. In order to improve surgical outcomes, a better understanding of postrepair histological and cellular responses at the tendon-bone attachment site (enthesis) is needed. We examined operated shoulders from 42 New Zealand female white rabbits. The animals underwent unilateral supraspinatus detachment followed by anchor repair a week later. To assess enthesis reformation, fibrocartilage staining area and the number of chondrocytes or nonchondrocytes were quantified at 0, 1, 2, and 4 weeks postrepair. Using linear regression, we correlated these results with the load to failure and stiffness recorded during mechanical testing of the tendons. Fibrocartilage staining and chondrocyte number increased during the first 2 weeks of enthesis formation. Between 2 and 4 weeks, fibrocartilage staining plateaued while chondrocyte number decreased. The presence of nonchondrocytes remained similar between 0- and 1-week postrepair but then decreased abruptly at 2 weeks. There was a linear correlation between fibrocartilage staining area and load to failure as well as stiffness. Nonchondrocyte number negatively correlated with stiffness. Early plateau of fibrocartilage staining and decrease in chondrocytes between 2 and 4 weeks postrepair suggest a blunted enthesis formation response in our animal model.
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Affiliation(s)
- T Mark Campbell
- Department of Physical Medicine and Rehabilitation, Elisabeth Bruyère Hospital, Ottawa, Ontario, Canada.,Bone and Joint Research Laboratory, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.,Division of Physical Medicine and Rehabilitation, Department of Medicine, The Ottawa Hospital Rehabilitation Centre, Ottawa, Ontario, Canada
| | - Le Gao
- Department of Biology, University of Ottawa, Ottawa, Ontario, Canada
| | - Odette Laneuville
- Department of Biology, University of Ottawa, Ottawa, Ontario, Canada
| | - Hakim Louati
- Bone and Joint Research Laboratory, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Hans K Uhthoff
- Bone and Joint Research Laboratory, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,Division of Orthopaedic Surgery, Department of Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Guy Trudel
- Bone and Joint Research Laboratory, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,Division of Physical Medicine and Rehabilitation, Department of Medicine, The Ottawa Hospital Rehabilitation Centre, Ottawa, Ontario, Canada.,Division of Orthopaedic Surgery, Department of Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada.,Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
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Huang C, Zhang X, Luo H, Pan J, Cui W, Cheng B, Zhao S, Chen G. Effect of kartogenin-loaded gelatin methacryloyl hydrogel scaffold with bone marrow stimulation for enthesis healing in rotator cuff repair. J Shoulder Elbow Surg 2021; 30:544-553. [PMID: 32650072 DOI: 10.1016/j.jse.2020.06.013] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 06/10/2020] [Accepted: 06/15/2020] [Indexed: 02/01/2023]
Abstract
BACKGROUND Strategies involving microfracture, biomaterials, growth factors, and chemical agents have been evaluated for improving enthesis healing. Kartogenin (KGN) promotes selective differentiation of bone marrow mesenchymal stem cells (BMSCs) into chondrocytes. Gelatin methacryloyl (GelMA) is a promising biomaterial for engineering scaffolds and drug carriers. Herein, we investigated KGN-loaded GelMA hydrogel scaffolds with a bone marrow-stimulating technique for the repair of rotator cuff tear. METHODS KGN-loaded GelMA hydrogel scaffolds were obtained by ultraviolet GelMA crosslinking and vacuum freeze-drying. Fifty-four New Zealand rabbits were randomly divided into (1) repair only (control), (2) microfracture + repair (BMS), and (3) microfracture + repair augmentation with a KGN-loaded GelMA hydrogel scaffold (combined) groups. Tendons were repaired by transosseous sutures. The structure, degradation, and in vitro KGN release of the scaffolds were characterized. Animals were euthanized 4, 8, and 12 weeks after repair. Enthesis healing was evaluated by macroscopy, microcomputed tomography, histology, and biomechanical tests. RESULTS The KGN-loaded GelMA hydrogel scaffolds are porous with a 60.4 ± 28.2-μm average pore size, and they degrade quickly in 2.5 units/mL collagenase solution. Nearly 81% of KGN was released into phosphate-buffered saline within 12 hours, whereas the remaining KGN was released in 7 days. Macroscopically, the repaired tendons were attached to the footprint. No differences were detected postoperatively in microcomputed tomography analysis among groups. Fibrous scar tissue was the main component at the tendon-to-bone interface in the control group. Disorderly arranged cartilage formation was observed at the tendon-to-bone interface in the BMS and combined groups 4 weeks after repair; the combined group exhibited relatively more cartilage. The combined group showed improved cartilage regeneration 8 and 12 weeks after repair. Similar results were found in tendon maturation scores. The ultimate load to failure and stiffness of the repaired tendon increased in all 3 groups. At 4 weeks after repair, the BMS and combined groups exhibited greater ultimate load to failure than the control group, although there was no difference in stiffness among groups. The BMS and combined groups exhibited greater ultimate load to failure and stiffness than the control group, and the combined group exhibited better values than the BMS group at 8 and 12 weeks after repair. CONCLUSION Compared with the bone marrow-stimulating technique, the KGN-loaded GelMA hydrogel scaffold with bone marrow stimulation improved enthesis healing by promoting fibrocartilage formation and improving the mechanical properties.
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Affiliation(s)
- Chenglong Huang
- Department of Orthopedics, Clinical Medical School, The Affiliated Shanghai No. 10 People's Hospital, Nanjing Medical University, Shanghai, China; Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China
| | - Xuancheng Zhang
- Department of Sports Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Huanhuan Luo
- Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China
| | - Jieen Pan
- Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China
| | - Wenguo Cui
- Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Biao Cheng
- Department of Orthopedics, Clinical Medical School, The Affiliated Shanghai No. 10 People's Hospital, Nanjing Medical University, Shanghai, China.
| | - Song Zhao
- Department of Sports Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
| | - Gang Chen
- Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China.
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Lei T, Zhang T, Ju W, Chen X, Heng BC, Shen W, Yin Z. Biomimetic strategies for tendon/ligament-to-bone interface regeneration. Bioact Mater 2021; 6:2491-2510. [PMID: 33665493 PMCID: PMC7889437 DOI: 10.1016/j.bioactmat.2021.01.022] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 01/04/2021] [Accepted: 01/20/2021] [Indexed: 12/19/2022] Open
Abstract
Tendon/ligament-to-bone healing poses a formidable clinical challenge due to the complex structure, composition, cell population and mechanics of the interface. With rapid advances in tissue engineering, a variety of strategies including advanced biomaterials, bioactive growth factors and multiple stem cell lineages have been developed to facilitate the healing of this tissue interface. Given the important role of structure-function relationship, the review begins with a brief description of enthesis structure and composition. Next, the biomimetic biomaterials including decellularized extracellular matrix scaffolds and synthetic-/natural-origin scaffolds are critically examined. Then, the key roles of the combination, concentration and location of various growth factors in biomimetic application are emphasized. After that, the various stem cell sources and culture systems are described. At last, we discuss unmet needs and existing challenges in the ideal strategies for tendon/ligament-to-bone regeneration and highlight emerging strategies in the field.
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Affiliation(s)
- Tingyun Lei
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine and Department of Orthopedic Surgery of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310058, China.,Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, 310058, China
| | - Tao Zhang
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine and Department of Orthopedic Surgery of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310058, China.,Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, 310058, China
| | - Wei Ju
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine and Department of Orthopedic Surgery of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310058, China.,Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, 310058, China
| | - Xiao Chen
- Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, 310058, China.,Department of Orthopedic Surgery of The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310052, China.,Department of Sports Medicine, School of Medicine, Zhejiang University, Hangzhou, 310058, China.,China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou, 310058, China
| | | | - Weiliang Shen
- Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, 310058, China.,Department of Orthopedic Surgery of The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310052, China.,Department of Sports Medicine, School of Medicine, Zhejiang University, Hangzhou, 310058, China.,China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou, 310058, China
| | - Zi Yin
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine and Department of Orthopedic Surgery of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310058, China.,Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, 310058, China.,Department of Sports Medicine, School of Medicine, Zhejiang University, Hangzhou, 310058, China.,China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou, 310058, China
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Bianchi E, Ruggeri M, Rossi S, Vigani B, Miele D, Bonferoni MC, Sandri G, Ferrari F. Innovative Strategies in Tendon Tissue Engineering. Pharmaceutics 2021; 13:89. [PMID: 33440840 PMCID: PMC7827834 DOI: 10.3390/pharmaceutics13010089] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 12/31/2020] [Accepted: 01/08/2021] [Indexed: 12/15/2022] Open
Abstract
The tendon is a highly aligned connective tissue that transmits force from muscle to bone. Each year, more than 32 million tendon injuries have been reported, in fact, tendinopathies represent at least 50% of all sports injuries, and their incidence rates have increased in recent decades due to the aging population. Current clinical grafts used in tendon treatment are subject to several restrictions and there is a significant demand for alternative engineered tissue. For this reason, innovative strategies need to be explored. Tendon replacement and regeneration are complex since scaffolds need to guarantee an adequate hierarchical structured morphology and mechanical properties to stand the load. Moreover, to guide cell proliferation and growth, scaffolds should provide a fibrous network that mimics the collagen arrangement of the extracellular matrix in the tendons. This review focuses on tendon repair and regeneration. Particular attention has been devoted to the innovative approaches in tissue engineering. Advanced manufacturing techniques, such as electrospinning, soft lithography, and three-dimensional (3D) printing, have been described. Furthermore, biological augmentation has been considered, as an emerging strategy with great therapeutic potential.
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Affiliation(s)
| | | | | | | | | | | | - Giuseppina Sandri
- Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy; (E.B.); (M.R.); (S.R.); (B.V.); (D.M.); (M.C.B.); (F.F.)
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50
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Blanton CM, Clougherty CO. The Role of Bone Marrow Aspirate in Osseous and Soft Tissue Pathology. Clin Podiatr Med Surg 2021; 38:1-16. [PMID: 33220739 DOI: 10.1016/j.cpm.2020.08.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Bone marrow aspirate (BMA) is an emerging therapy that is gaining popularity for orthoplastic reconstruction. The stem cells collected are multipotent and regenerative in nature. In addition to stem cells, other biological components collected augment the mitogen of local cells, proliferation, and angiogenesis, and inhibit proinflammatory cytokine and bacteria to optimize an environment to heal. The most common site for harvest is the iliac crest. Techniques for harvesting BMA are simple to perform, financially modest, and associated with low morbidity. Additional research is needed to evolve and standardize the technology; however, BMA is proven to be advantageous for tissue repair.
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Affiliation(s)
- Casie M Blanton
- The Reconstruction Institute of The Bellevue Hospital, 102 Commerce Park Drive, Suite D, Bellevue, OH 44811, USA.
| | - Coleman O Clougherty
- The Reconstruction Institute of The Bellevue Hospital, 102 Commerce Park Drive, Suite D, Bellevue, OH 44811, USA
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