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Zhang B, Dong B, Wang L, Wang Y, Gao Z, Li Y, Wang H, Lu X. Comparison of the efficacy of autologous Lp-PRP and Lr-PRP for treating intervertebral disc degeneration: in vitro and in vivo study. J Orthop Surg Res 2024; 19:731. [PMID: 39506797 PMCID: PMC11542231 DOI: 10.1186/s13018-024-05196-8] [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: 10/03/2024] [Accepted: 10/20/2024] [Indexed: 11/08/2024] Open
Abstract
BACKGROUND Intervertebral disc degeneration (IDD) was the most common cause of low back pain. Platelet rich plasma (PRP) has the potential to repair IDD, however, there is still no conclusion on whether Leukocyte-poor platelet rich plasma (Lp-PRP) or Leukocyte-rich platelet rich plasma (Lr-PRP) is better for the treatment of IDD. METHODS First, we conducted an in vitro study to compare the effects of autologous Lp-PRP and Lr-PRP on human degenerated nucleus pulposus (NP) cells. Then we verified the in vivo effects of autologous Lp-PRP and Lr-PRP in treating disc degeneration through a rabbit IDD model. RESULTS The in vitro study showed both autologous Lp-PRP and Lr-PRP can promote the cell proliferation, the synthesis of COL II and Aggrecan of human degenerated NP cells, while Lp-PRP are better than Lr-PRP (P<0.05). In addition, only Lp-PRP can inhibit the apoptosis of human degenerated NP cells (P<0.05), whereas Lr-PRP activates the catabolism on the contrary (P<0.05). Further, the in vivo study through the rabbit IDD model verified that autologous Lp-PRP has better effects than autologous Lr-PRP in repairing IDD according to X-ray, MRI, histological, and immunohistochemical assessment (P<0.05, respectively). And the caspase-3 IHC results also showed that only autologous Lp-PRP treatment could inhibit apoptosis of NP cells in the rabbit IDD model (P<0.05). CONCLUSION Combining in vivo and in vitro studies, the present study confirmed that autologous Lp-PRP has a better effect than autologous Lr-PRP in repairing IDD, which may be due to the inflammatory factors (TNFα, IL-1β, etc.) in Lr-PRP antagonizing part of the repair effects and promoting the catabolism additionally. Therefore, our findings suggest that Lp-PRP may provide better results than Lr-PRP for treating IDD. Further randomized clinical trials will provide evidence to guide practice.
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Affiliation(s)
- Bangke Zhang
- Department of Orthopaedics, Shanghai Changzheng Hospital, Navy Medical University, No. 415, Feng Yang Street, Huangpu District, Shanghai, 200003, P.R. China
| | | | - Liang Wang
- Department of Orthopaedics, Shanghai Changzheng Hospital, Navy Medical University, No. 415, Feng Yang Street, Huangpu District, Shanghai, 200003, P.R. China
| | - Yijin Wang
- Department of Orthopaedics, Shanghai Changzheng Hospital, Navy Medical University, No. 415, Feng Yang Street, Huangpu District, Shanghai, 200003, P.R. China
| | - Zhongya Gao
- Department of Orthopaedics, Shanghai Changzheng Hospital, Navy Medical University, No. 415, Feng Yang Street, Huangpu District, Shanghai, 200003, P.R. China
| | - Yang Li
- Department of Orthopaedics, Shanghai Changzheng Hospital, Navy Medical University, No. 415, Feng Yang Street, Huangpu District, Shanghai, 200003, P.R. China
| | - Haibin Wang
- Department of Orthopaedics, Shanghai Changzheng Hospital, Navy Medical University, No. 415, Feng Yang Street, Huangpu District, Shanghai, 200003, P.R. China.
| | - Xuhua Lu
- Department of Orthopaedics, Shanghai Changzheng Hospital, Navy Medical University, No. 415, Feng Yang Street, Huangpu District, Shanghai, 200003, P.R. China.
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Cantero MM. Not all platelet-rich plasma are created equal. Curr Opin Obstet Gynecol 2024; 36:118-123. [PMID: 38324593 DOI: 10.1097/gco.0000000000000944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2024]
Abstract
PURPOSE OF REVIEW This review aims to elucidate potential variations in clinical outcomes resulting from the use of different types of platelet-rich plasma (PRPs) in reproductive medicine. It seeks to explore the reasons behind the diverse results reported in various studies and assess the general features distinguishing different PRP formulations. RECENT FINDINGS PRPs have found applications across diverse medical fields, generating controversy due to the variability in outcomes. The field of reproductive medicine, despite its limited published studies, is encountering a similar challenge as it integrates these treatments. SUMMARY The multitude of PRP product brands in the market, coupled with 'home-made' PRPs, poses a significant barrier to establishing a common protocol for the preparation of standardized PRP products. This impediment hinders widespread adoption by clinicians, particularly in endometrial or ovarian treatments. Drawing from evidence in other medical disciplines, this review endeavors to compile essential characteristics that PRPs must possess, aiming to mitigate the impact of variables affecting results in forthcoming studies.
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Affiliation(s)
- Manuel Muñoz Cantero
- IVI Alicante, Centro de Excelencia en Rejuvenecimiento Ovárico, Avenida de Denia, Alicante, Spain
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3
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Chalidis B, Givissis P, Papadopoulos P, Pitsilos C. Molecular and Biologic Effects of Platelet-Rich Plasma (PRP) in Ligament and Tendon Healing and Regeneration: A Systematic Review. Int J Mol Sci 2023; 24:2744. [PMID: 36769065 PMCID: PMC9917492 DOI: 10.3390/ijms24032744] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 01/27/2023] [Accepted: 01/27/2023] [Indexed: 02/04/2023] Open
Abstract
Platelet-rich plasma (PRP) has been introduced and applied to a wide spectrum of acute and chronic ligament and tendon pathologic conditions. Although the biological effect of PRP has been studied thoroughly in both animal and human studies, there is no consensus so far on the exact mechanism of its action as well as the optimal timing and dosage of its application. Therefore, we conducted a systematic review aiming to evaluate the molecular effect of the administration of PRP in tendoligamentous injuries and degenerative diseases. The literature search revealed 36 in vitro and in vivo studies examining the healing and remodeling response of animal and human ligament or tendon tissues to PRP. Platelet-rich plasma added in the culture media was highly associated with increased cell proliferation, migration, viability and total collagen production of both ligament- and tendon-derived cells in in vitro studies, which was further confirmed by the upregulation of collagen gene expression. In vivo studies correlated the PRP with higher fibroblastic anabolic activity, including increased cellularity, collagen production and vascularity of ligament tissue. Similarly, greater metabolic response of tenocytes along with the acceleration of the healing process in the setting of a tendon tear were noticed after PRP application, particularly between the third and fourth week after treatment. However, some studies demonstrated that PRP had no or even negative effect on tendon and ligament regeneration. This controversy is mainly related to the variable processes and methodologies of preparation of PRP, necessitating standardized protocols for both investigation and ap-plication.
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Affiliation(s)
- Byron Chalidis
- 1st Orthopaedic Department, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece
| | - Panagiotis Givissis
- 1st Orthopaedic Department, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece
| | - Pericles Papadopoulos
- 2nd Orthopaedic Department, Aristotle University of Thessaloniki, 54635 Thessaloniki, Greece
| | - Charalampos Pitsilos
- 2nd Orthopaedic Department, Aristotle University of Thessaloniki, 54635 Thessaloniki, Greece
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Platelet-rich Plasma in the Management of Shoulder Disorders: Basic Science and Implications Beyond the Rotator Cuff. J Am Acad Orthop Surg 2022; 30:e1217-e1226. [PMID: 35947829 DOI: 10.5435/jaaos-d-22-00066] [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: 01/24/2022] [Accepted: 05/22/2022] [Indexed: 02/01/2023] Open
Abstract
Platelet-rich plasma (PRP) is an autologous mixture produced by centrifugal separation of whole blood. Understanding the clinical efficacy of PRP remains a challenge in the field of sports medicine, including the treatment of various shoulder conditions. Animal studies have examined the biologic actions of PRP on the rotator cuff tendon and shoulder capsule. Human studies have reported the outcomes of PRP in the management of subacromial impingement syndrome, rotator cuff tears, frozen shoulder, and glenohumeral osteoarthritis. These studies highlight the role of PRP in the nonsurgical management of these conditions and its utilization in the perioperative setting to augment tissue healing and optimize the surgical outcomes. The role of PRP as an adjunct therapy in patients undergoing rotator cuff repair has been in the spotlight during the last decade; however, a limited number of studies have examined the role of PRP in the management of non-rotator cuff shoulder conditions. This article aims to provide an overview of the biologic actions of PRP on shoulder tissues and to summarize the outcomes of PRP injection in patients with rotator cuff and non-rotator cuff disease of the shoulder. We sought to organize the existing literature and to provide recommendations on the use of PRP in various shoulder conditions, based on the existing evidence.
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Effect of Leukoreduced Platelet Rich Plasma on Intra-Articular Pro-Inflammatory Cytokines in a Canine Pilot Study. Animals (Basel) 2022; 12:ani12172163. [PMID: 36077884 PMCID: PMC9454790 DOI: 10.3390/ani12172163] [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] [Received: 07/07/2022] [Revised: 08/09/2022] [Accepted: 08/22/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary This study provides initial information on the effect of platelet rich plasma in some of the most important pro-inflammatory cytokines identified in osteoarthritic stifle joint in dogs. The use of platelet rich plasma is getting more popular in the veterinary field but its effect in those cytokines is not known. Abstract Evaluation of effect of Leukoreduced Platelet Rich Plasma (LrPRP) on TNF-α and IL-6 (pro-inflammatory cytokines) in joint fluid in dogs with cranial cruciate ligament rupture (CCLR). Eight client-owned dogs with CCLR were assigned to treatment (2 mL LrPRP) or control (2 mL saline) injection groups. Day of evaluation (day 0) and day of surgery (day 10–14), joint fluid was collected and joint injected. Joint fluid was also collected on day of suture removal (day 20–28). TNF-α and IL-6 concentrations of joint fluid were measured using a bead-based antibody assay. Concentrations at the later time points were expressed as a ratio to the initial level within each stifle. LrPRP had a mean concentration of platelets 1.7 times higher that of whole blood on day of evaluation and 1.4 times higher on day of the surgery. Leukocytes were reduced by 99.7%. On day of surgery, TNF-α ratios in the joint fluid from dogs injected with LrPRP were significantly different that TNF-α ratios of control group. On the day of suture removal ratios of IL-6 and TNF-α were lower in LrPRP treatment group compared with control group; however, differences were not significant. LrPRP modulate ratios of pro-inflammatory cytokine TNF-α in dogs with CCLR.
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Kunze KN, Pakanati JJ, Vadhera AS, Polce EM, Williams BT, Parvaresh KC, Chahla J. The Efficacy of Platelet-Rich Plasma for Ligament Injuries: A Systematic Review of Basic Science Literature With Protocol Quality Assessment. Orthop J Sports Med 2022; 10:23259671211066504. [PMID: 35155701 PMCID: PMC8832618 DOI: 10.1177/23259671211066504] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 09/27/2021] [Indexed: 02/01/2023] Open
Abstract
Background: Despite the existence of many clinical studies on platelet-rich plasma (PRP) interventions for ligamentous pathology, basic science consensus regarding the indications, mechanisms, and optimal composition of PRP for treating ligament injuries is lacking. Purpose: To (1) compare the efficacy of PRP in animal models of ligament injury with placebo and (2) describe the potential variability in PRP preparation using accepted classification systems. Study Design: Systematic review. Methods: The Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, PubMed, Embase, and Ovid MEDLINE were queried in April 2020 for in vivo and in vitro basic science studies regarding PRP use for ligament injury. Study design, results, PRP composition, and analyzed cellular and molecular markers were extracted, and outcomes relative to control models were documented. Bias was assessed using the SYRCLE risk-of-bias tool. Results: Included were 43 articles (31 in vivo and 12 in vitro studies) investigating the anterior cruciate ligament/cranial cruciate ligament (n = 32), medial collateral ligament (n = 6), suspensory ligament (n = 3), patellar ligament (n = 1), and Hock ligament (n = 1). Platelet concentration was reported in 34 studies (77.3%); leukocyte composition, in 12 (27.3%); and red blood cell counts, in 7 (15.9%). With PRP treatment, 5 of 12 in vitro studies demonstrated significant increases in cell viability, 6 of 12 in gene expression, 14 of 32 in vivo studies reported superior ligament repair via histological evaluation, and 13 in vivo studies reported superior mechanical properties. Variability in PRP preparation methods was observed across all articles, and only 1 study reported all necessary information to be classified by the 4 schemes we used to evaluate reporting. Among the in vivo studies, detection and performance bias were consistently high, whereas selection, attrition, reporting, and other biases were consistently low. Conclusion: Conflicting data on the cellular and molecular effects of PRP for ligament injuries were observed secondary to the finding that included studies were heterogeneous, limiting interpretation across studies and the ability to draw meaningful conclusions. Clinical trials and any causal relationship between PRP use in ligament injuries and its potential for regeneration and healing should be pursued with caution if based solely on basic science data.
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Affiliation(s)
- Kyle N. Kunze
- Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, New York, USA
| | - Jeevana J. Pakanati
- Rosalind Franklin University, Chicago Medical School, Chicago, Illinois, USA
| | - Amar S. Vadhera
- Department of Orthopaedic Surgery, Division of Sports Medicine, Rush University Medical Center, Chicago, Illinois, USA
| | - Evan M. Polce
- University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Brady T. Williams
- Department of Orthopaedic Surgery, University of Colorado, Aurora, Colorado, USA
| | - Kevin C. Parvaresh
- Department of Orthopaedic Surgery, Division of Sports Medicine, Rush University Medical Center, Chicago, Illinois, USA
| | - Jorge Chahla
- Department of Orthopaedic Surgery, Division of Sports Medicine, Rush University Medical Center, Chicago, Illinois, USA
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Murray MM. Optimizing outcomes of ACL surgery-Is autograft reconstruction the only reasonable option? J Orthop Res 2021; 39:1843-1850. [PMID: 34191344 PMCID: PMC8387392 DOI: 10.1002/jor.25128] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 06/25/2021] [Indexed: 02/04/2023]
Abstract
Anterior cruciate ligament (ACL) injuries occur at a high frequency in the United States with approximately 400,000 ACL reconstructions being performed each year. While ACL reconstruction is our current gold standard of treatment, it does not restore joint motion, or prevent the premature development of posttraumatic osteoarthritis (PTOA) in many patients. Thus, new treatments for an ACL injury, which are less invasive and minimize patient morbidity, including cartilage damage, are highly desirable. We have used a tissue-engineered approach to stimulate ligament healing, to improve upon current treatment options. In this review, we describe and discuss our work moving a tissue engineering strategy from the concept to bench, preclinical, clinical trials and ultimately FDA 510(k) de Novo approval, providing clinicians and patients with a viable alternative to ACL reconstruction.
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Affiliation(s)
- Martha M. Murray
- Department of Orthopaedic Surgery, Division of Sports Medicine, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA
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Millan SM, Thorn D, Ford E. A Novel Approach to Augmenting Allograft Hamstring Anterior Cruciate Ligament Reconstructions Utilizing a Resorbable Type I Collagen Matrix with Platelet Rich Plasma. Case Rep Orthop 2021; 2021:5574676. [PMID: 33777468 PMCID: PMC7972856 DOI: 10.1155/2021/5574676] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 02/06/2021] [Accepted: 03/03/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Anterior cruciate ligament reconstruction (ACLR) is one of the most common lower extremity orthopedic surgeries performed in the United States. Annually, between 100,000 and 200,000 ACL tears affect 1 in 3,000 people. The selection of autograft versus allograft for ACLR has been widely discussed in terms of risk of graft failure. Allograft reconstructions have been shown to have higher rerupture rates. One factor contributing to this risk is delayed biologic graft incorporation. METHODS A retrospective review was performed examining 14 patients who underwent an augmented quadruple-stranded hamstring allograft ACLR with a type I resorbable collagen matrix impregnated with platelet-rich plasma (PRP). RESULTS Within our clinical practice, the augmentation of quadruple-stranded hamstring allograft ACLR with a type I resorbable matrix impregnated with PRP has yielded good early clinical success at 2-year outcomes (N = 14). Zero ACLR failures have been reported to date in this series. CONCLUSION This case series offers a novel approach for soft tissue allograft ACLR augmented with a type I collagen matrix impregnated with PRP. The authors theorize that this augmentation may improve biologic graft incorporation into the host bone tunnels.
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Affiliation(s)
- Sean Mc Millan
- Department of Orthopedics, Virtua Health System, 2103 Burlington-Mount Holly Rd, Burlington, NJ 08016, USA
| | - Danielle Thorn
- Department of Orthopedics, Virtua Health System, Burlington, NJ, USA
| | - Elizabeth Ford
- Department of Orthopedics, Inspira Health System, Vineland, NJ, USA
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Devereaux J, Dargahi N, Fraser S, Nurgali K, Kiatos D, Apostolopoulos V. Leucocyte-Rich Platelet-Rich Plasma Enhances Fibroblast and Extracellular Matrix Activity: Implications in Wound Healing. Int J Mol Sci 2020; 21:ijms21186519. [PMID: 32900003 PMCID: PMC7556022 DOI: 10.3390/ijms21186519] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 09/03/2020] [Accepted: 09/04/2020] [Indexed: 12/16/2022] Open
Abstract
Background: Platelet-rich plasma (PRP) is an autologous blood product that contains a high concentration of platelets and leucocytes, which are fundamental fibroblast proliferation agents. Literature has emerged that offers contradictory findings about leucocytes within PRP. Herein, we elucidated the effects of highly concentrated leucocytes and platelets on human fibroblasts. Methods: Leucocyte-rich, PRP (LR-PRP) and leucocyte-poor, platelet-poor plasma (LP-PPP) were compared to identify their effects on human fibroblasts, including cell proliferation, wound healing and extracellular matrix and adhesion molecule gene expressions. Results: The LR-PRP exhibited 1422.00 ± 317.21 × 103 platelets/µL and 16.36 ± 2.08 × 103 white blood cells/µL whilst the LP-PPP demonstrated lower concentrations of 55.33 ± 10.13 × 103 platelets/µL and 0.8 ± 0.02 × 103 white blood cells/µL. LR-PRP enhanced fibroblast cell proliferation and cell migration, and demonstrated either upregulation or down-regulation gene expression profile of the extracellular matrix and adhesion molecules. Conclusion: LR-PRP has a continuous stimulatory anabolic and ergogenic effect on human fibroblast cells.
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Affiliation(s)
- Jeannie Devereaux
- College of Health and Biomedicine, Victoria University, Melbourne, VIC 3011, Australia;
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3011, Australia; (N.D.); (S.F.); (K.N.)
- Correspondence: (J.D.); (V.A.); Tel.: +613-83958218 (J.D.); +613-99192025 (V.A.)
| | - Narges Dargahi
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3011, Australia; (N.D.); (S.F.); (K.N.)
| | - Sarah Fraser
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3011, Australia; (N.D.); (S.F.); (K.N.)
| | - Kulmira Nurgali
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3011, Australia; (N.D.); (S.F.); (K.N.)
| | - Dimitrios Kiatos
- College of Health and Biomedicine, Victoria University, Melbourne, VIC 3011, Australia;
| | - Vasso Apostolopoulos
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3011, Australia; (N.D.); (S.F.); (K.N.)
- Correspondence: (J.D.); (V.A.); Tel.: +613-83958218 (J.D.); +613-99192025 (V.A.)
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Perego R, Spada E, Baggiani L, Martino PA, Proverbio D. Efficacy of a Semi Automated Commercial Closed System for Autologous Leukocyte- and Platelet-Rich Plasma (l-prp) Production in Dogs: A Preliminary Study. Animals (Basel) 2020; 10:ani10081342. [PMID: 32759643 PMCID: PMC7459512 DOI: 10.3390/ani10081342] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 07/30/2020] [Accepted: 08/01/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND To characterize the cellular composition (platelets, erythrocytes, and leukocytes) and determine platelet-derived growth factor isoform BB (PDGF-BB) concentration in canine leukocyte- and platelet rich plasma (L-PRP) produced using a commercial semi-automated closed system. METHODS Twenty milliliters of citrated whole blood were obtained from 30 healthy un-sedated canine blood donors and processed using a semi-automated completely closed commercial system (CPUNT 20, Eltek group, Casale Monferrato, Alessandria, Italy) according to the manufacturer's instructions. Erythrocyte, leukocyte, and platelet counts were determined in both whole blood (WB) and resultant L-PRP. The PDGF-BB concentration was evaluated after bovine thrombin activation of 10 L-PRP samples. RESULTS This commercial system produced on average 2.3 ± 0.7 mL of L-PRP containing a high concentration of platelets (767,633 ± 291,001 μL, p < 0.001), with a 4.4 fold increase in platelet count, lower concentration of erythrocytes (528,600 ± 222,773 μL, p < 0.001) and similar concentration of leukocytes (8422 ± 6346 μL, p = 0.9918) compared with WB. L-PRP had an average of 3442 ± 2061 pg/mL of PDGF-BB after thrombin activation. Neutrophils, lymphocytes and monocytes average percent content in L-PRP was 14.8 ± 13.2, 71.7 ± 18.5 and 10.7 ± 6.4, respectively. CONCLUSION Sterile canine L-PRP prepared using this semi-automated closed system is easy to obtain, produces a significant increase in platelet count compared to WB and contains a detectable concentration of PDGF-BB after activation. Additional in vitro and in vivo studies are needed to assess inflammatory markers concentration and the therapeutic efficacy of this L-PRP in dogs.
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Affiliation(s)
- Roberta Perego
- Veterinary Transfusion Research Laboratory (REVLab), Department of Veterinary Medicine (DIMEVET), University of Milan, via dell’Università 6, 26900 Lodi, Italy; (L.B.); (D.P.)
- Correspondence: (R.P.); (E.S.); Tel.: +39-0250334521 (R.P.); +39-0250334520 (E.S.)
| | - Eva Spada
- Veterinary Transfusion Research Laboratory (REVLab), Department of Veterinary Medicine (DIMEVET), University of Milan, via dell’Università 6, 26900 Lodi, Italy; (L.B.); (D.P.)
- Correspondence: (R.P.); (E.S.); Tel.: +39-0250334521 (R.P.); +39-0250334520 (E.S.)
| | - Luciana Baggiani
- Veterinary Transfusion Research Laboratory (REVLab), Department of Veterinary Medicine (DIMEVET), University of Milan, via dell’Università 6, 26900 Lodi, Italy; (L.B.); (D.P.)
| | - Piera Anna Martino
- Department of Veterinary Medicine (DIMEVET), University of Milan, via dell’Università 6, 26900 Lodi, Italy;
| | - Daniela Proverbio
- Veterinary Transfusion Research Laboratory (REVLab), Department of Veterinary Medicine (DIMEVET), University of Milan, via dell’Università 6, 26900 Lodi, Italy; (L.B.); (D.P.)
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Freiberger C, Kiapour AM, Liu S, Henderson RN, Barnett S, Sant NJ, Proffen BL, Fleming BC, Ecklund K, Kramer DE, Micheli LJ, Murray MM, Yen YM. Higher Physiologic Platelet Counts in Whole Blood Are Not Associated With Improved ACL Cross-sectional Area or Signal Intensity 6 Months After Bridge-Enhanced ACL Repair. Orthop J Sports Med 2020; 8:2325967120927655. [PMID: 32656289 PMCID: PMC7331772 DOI: 10.1177/2325967120927655] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 02/21/2020] [Indexed: 01/08/2023] Open
Abstract
Background: A bridge-enhanced anterior cruciate ligament (ACL) repair (BEAR) procedure places an extracellular matrix implant, combined with autologous whole blood, in the gap between the torn ends of the ligament at the time of suture repair to stimulate healing. Prior studies have suggested that white blood cell (WBC) and platelet concentrations significantly affect the healing of other musculoskeletal tissues. Purpose/Hypothesis: The purpose of this study was to determine whether concentrations of various blood cell types placed into a bridging extracellular matrix implant at the time of ACL repair would have a significant effect on the healing ligament cross-sectional area or tissue organization (as measured by signal intensity). We hypothesized that patients with higher physiologic platelet and lower WBC counts would have improved healing of the ACL on magnetic resonance imaging (MRI) (higher cross-sectional area and/or lower signal intensity) 6 months after surgery. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 61 patients underwent MRI at 6 months after bridge-enhanced ACL repair as part of the BEAR II trial. The normalized signal intensity and average cross-sectional area of the healing ligament were measured from a magnetic resonance stack obtained using a gradient echo sequence. The results were stratified by sex, and univariate and multivariate regression analyses determined significant correlations between blood cell concentrations on these 2 magnetic resonance parameters. Results: In unadjusted analyses, older age and male sex were associated with greater healing ligament cross-sectional area (P < .04) but not signal intensity (P > .15). Adjusted multivariable analyses indicated that in female patients, a higher monocyte concentration correlated with a higher ACL cross-sectional area (β = 1.01; P = .049). All other factors measured, including the physiologic concentration of platelets, neutrophils, lymphocytes, basophils, and immunoglobulin against bovine gelatin, were not significantly associated with either magnetic resonance parameter in either sex (P > .05 for all). Conclusion: Although older age, male sex, and monocyte concentration in female patients were associated with greater healing ligament cross-sectional area, signal intensity of the healing ligament was independent of these factors. Physiologic platelet concentration did not have any significant effect on cross-sectional area or signal intensity of the healing ACL at 6 months after bridge-enhanced ACL repair in this cohort. Given these findings, factors other than the physiologic platelet concentration and total WBC concentration may be more important in the rate and amount of ACL healing after bridge-enhanced ACL repair.
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Affiliation(s)
- Christina Freiberger
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Ata M Kiapour
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Shanshan Liu
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | | | - Rachael N Henderson
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Samuel Barnett
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Nicholas J Sant
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Benedikt L Proffen
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Braden C Fleming
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Kirsten Ecklund
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Dennis E Kramer
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Lyle J Micheli
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Martha M Murray
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Yi-Meng Yen
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
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Murray MM, Fleming BC, Badger GJ, Freiberger C, Henderson R, Barnett S, Kiapour A, Ecklund K, Proffen B, Sant N, Kramer DE, Micheli LJ, Yen YM. Bridge-Enhanced Anterior Cruciate Ligament Repair Is Not Inferior to Autograft Anterior Cruciate Ligament Reconstruction at 2 Years: Results of a Prospective Randomized Clinical Trial. Am J Sports Med 2020; 48:1305-1315. [PMID: 32298131 PMCID: PMC7227128 DOI: 10.1177/0363546520913532] [Citation(s) in RCA: 135] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Preclinical studies suggest that for complete midsubstance anterior cruciate ligament (ACL) injuries, a suture repair of the ACL augmented with a protein implant placed in the gap between the torn ends (bridge-enhanced ACL repair [BEAR]) may be a viable alternative to ACL reconstruction (ACLR). HYPOTHESIS We hypothesized that patients treated with BEAR would have a noninferior patient-reported outcomes (International Knee Documentation Committee [IKDC] Subjective Score; prespecified noninferiority margin, -11.5 points) and instrumented anteroposterior (AP) knee laxity (prespecified noninferiority margin, +2-mm side-to-side difference) and superior muscle strength at 2 years after surgery when compared with patients who underwent ACLR with autograft. STUDY DESIGN Randomized controlled trial; Level of evidence, 1. METHODS One hundred patients (median age, 17 years; median preoperative Marx activity score, 16) with complete midsubstance ACL injuries were enrolled and underwent surgery within 45 days of injury. Patients were randomly assigned to receive either BEAR (n = 65) or autograft ACLR (n = 35 [33 with quadrupled semitendinosus-gracilis and 2 with bone-patellar tendon-bone]). Outcomes-including the IKDC Subjective Score, the side-to-side difference in instrumented AP knee laxity, and muscle strength-were assessed at 2 years by an independent examiner blinded to the procedure. Patients were unblinded after their 2-year visit. RESULTS In total, 96% of the patients returned for 2-year follow-up. Noninferiority criteria were met for both the IKDC Subjective Score (BEAR, 88.9 points; ACLR, 84.8 points; mean difference, 4.1 points [95% CI, -1.5 to 9.7]) and the side-to-side difference in AP knee laxity (BEAR, 1.61 mm; ACLR, 1.77 mm; mean difference, -0.15 mm [95% CI, -1.48 to 1.17]). The BEAR group had a significantly higher mean hamstring muscle strength index than the ACLR group at 2 years (98.2% vs 63.2%; P < .001). In addition, 14% of the BEAR group and 6% of the ACLR group had a reinjury that required a second ipsilateral ACL surgical procedure (P = .32). Furthermore, the 8 patients who converted from BEAR to ACLR in the study period and returned for the 2-year postoperative visit had similar primary outcomes to patients who had a single ipsilateral ACL procedure. CONCLUSION BEAR resulted in noninferior patient-reported outcomes and AP knee laxity and superior hamstring muscle strength when compared with autograft ACLR at 2-year follow-up in a young and active cohort. These promising results suggest that longer-term studies of this technique are justified. REGISTRATION NCT02664545 (ClinicalTrials.gov identifier).
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Affiliation(s)
- Martha M. Murray
- Martha M. Murray, MD, Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children’s Hospital, 300 Longwood Ave, Hunnewell 2, Boston, MA 02115, USA ()
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Berdis AS, Veale K, Fleissner PR. Outcomes of Anterior Cruciate Ligament Reconstruction Using Biologic Augmentation in Patients 21 Years of Age and Younger. Arthroscopy 2019; 35:3107-3113. [PMID: 31439458 DOI: 10.1016/j.arthro.2019.05.047] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 05/21/2019] [Accepted: 05/23/2019] [Indexed: 02/02/2023]
Abstract
PURPOSE To report on the outcomes of a subset of patients ≤21 years of age after anterior cruciate ligament (ACL) reconstruction coupled with biologic augmentation using platelet-rich plasma (PRP) and a porous collagen carrier. METHODS A cohort of patients was retrospectively reviewed after ACL reconstruction with hamstring autograft tendon. All reconstructive surgeries combined biologic augmentation in which the ACL graft was coupled with PRP contained within porous collagen membrane. Patients were included if they maintained a minimum follow-up period of 24 months. Outcomes were assessed through patient-reported questionnaires and physical examination in the clinical setting. Patient-reported outcomes including International Knee Documentation Committee (IKDC), Lysholm, Tegner, and Single Assessment Numeric Evaluation (SANE) scores were collected. ACL stability was evaluated using Lachman and KT-1000 testing. Patients were also evaluated for return to play at the same level of competition, family history of ACL injury, and time to complete rehabilitation. RESULTS A total of 194 patients were initially eligible; 143 (74%) patients with 151 knees were ultimately evaluated. The average patient age was 16 years; 79 patients were female and 64 were male. Follow-up duration averaged 52 months. IKDC and Lysholm scores averaged 91 and 91; the average SANE score was 94. The KT-1000 side-to-side difference averaged 1.2 mm. The average time to complete physical therapy was 22 weeks, and 132 patients (92%) returned to their preinjury level of competition. There were 23 cases of contralateral ACL injury (15%) and 7 cases of ACL reinjury necessitating revision surgery (5%). CONCLUSIONS Biologic augmentation with hamstring autograft in ACL reconstruction shows a decreased rate of second ACL injury, specifically with regard to ACL revision surgery. The patients in this study also show higher return to preinjury level of competition at a faster rate than other studies have shown. LEVEL OF EVIDENCE Level IV, Therapeutic Case Series.
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Affiliation(s)
- Anthony S Berdis
- Department of Graduate Medical Education, Aultman Hospital, Canton, Ohio, U.S.A..
| | - Kodi Veale
- Crystal Clinic Orthopaedic Center, Bell Chapter of the Hawkins Foundation, Akron, Ohio, U.S.A
| | - Paul R Fleissner
- Crystal Clinic Orthopaedic Center, Bell Chapter of the Hawkins Foundation, Akron, Ohio, U.S.A
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Murray MM, Kalish LA, Fleming BC, Flutie B, Freiberger C, Henderson RN, Perrone GS, Thurber LG, Proffen BL, Ecklund K, Kramer DE, Yen YM, Micheli LJ. Bridge-Enhanced Anterior Cruciate Ligament Repair: Two-Year Results of a First-in-Human Study. Orthop J Sports Med 2019; 7:2325967118824356. [PMID: 30923725 PMCID: PMC6431773 DOI: 10.1177/2325967118824356] [Citation(s) in RCA: 107] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Background Bridge-enhanced anterior cruciate ligament repair (BEAR) combines suture repair of the anterior cruciate ligament (ACL) with a specific extracellular matrix scaffold (the BEAR scaffold) that is placed in the gap between the torn ends of the ACL to facilitate ligament healing. Purpose/Hypothesis The purpose of this study was to report the 12- and 24-month outcomes of patients who underwent the BEAR procedure compared with a nonrandomized concurrent control group who underwent ACL reconstruction (ACLR) with an autograft. We hypothesized that the BEAR group would have physical examination findings, patient-reported outcomes, and adverse events that were similar to those of the ACLR group. Study Design Cohort study; Level of evidence, 2. Methods Ten patients underwent BEAR, and 10 underwent ACLR with a 4-stranded hamstring autograft. At 24 months, 9 of the 10 BEAR patients and 7 of the 10 ACLR patients completed a study visit. Outcomes reported included International Knee Documentation Committee (IKDC) subjective and objective results, knee anteroposterior (AP) laxity findings via an arthrometer, and functional outcomes. Results There were no graft or repair failures in the first 24 months after surgery. The IKDC subjective scores in both groups improved significantly from baseline (P < .0001) at 12 and 24 months, to 84.6 ± 17.2 in the ACLR group and to 91.7 ± 11.7 in the BEAR group. An IKDC objective grade of A (normal) was found in 44% of patients in the BEAR group and in 29% of patients in the ACLR group at 24 months; no patients in either group had C (abnormal) or D (severely abnormal) grades. Arthrometer testing demonstrated mean side-to-side differences in AP laxity that were similar in the 2 groups at 24 months (BEAR, 1.94 ± 2.08 mm; ACLR, 3.14 ± 2.66 mm). Functional hop testing results were similar in the 2 groups at 12 and 24 months after surgery. Hamstring strength indices were significantly higher in the BEAR group compared with the ACLR group (P = .0001). Conclusion In this small, first-in-human study, BEAR produced similar outcomes to ACLR with a hamstring autograft. BEAR may result in knee stability and patient-reported outcomes at 2 years sufficient to warrant longer term studies of efficacy in larger groups of patients.
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Affiliation(s)
- Martha M Murray
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Leslie A Kalish
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Braden C Fleming
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | | | - Brett Flutie
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Christina Freiberger
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Rachael N Henderson
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Gabriel S Perrone
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Laura G Thurber
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Benedikt L Proffen
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Kirsten Ecklund
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Dennis E Kramer
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Yi-Meng Yen
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Lyle J Micheli
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
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Injecting autologous platelet rich plasma solely into the knee joint is not adequate in treating geriatric patients with moderate to severe knee osteoarthritis. Exp Gerontol 2019; 119:1-6. [PMID: 30664923 DOI: 10.1016/j.exger.2019.01.018] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Revised: 12/25/2018] [Accepted: 01/15/2019] [Indexed: 01/23/2023]
Abstract
Knee pain caused by osteoarthritis (OA) is commonly seen in geriatric patients. Patients with knee OA are often complicated with joint pain, soreness, and weakness. The injection of autologous platelet rich plasma (aPRP) has been proven to be effective in treating mild knee OA. The effect of injecting aPRP in treating moderate to severe degrees of knee OA remains controversial. This study aimed to evaluate the effectiveness of aPRP in treating patients with at least grade 2 on the Kellgren and Lawrence system for the classification of knee OA using a proteomic approach and clinical evaluation tool of Lequesne index. Musculoskeletal ultrasound was used for accurate needle placement into the knee joint, and to the perimeniscal soft tissue for the injection of aPRP. Three monthly aPRP injections were performed. Group 1 patients received intra-articular (IA) injection only, while group 2 received simultaneous IA and pes anserinus aPRP injections. After two monthly aPRP injections, both groups revealed significant drops in average SF total protein concentrations, and increases in the protein concentrations associated with chelation and anti-aging (eg/transthyretin, matrilin, and complement). However, it is group 2 that revealed significant decreases in the protein concentrations associated with inflammation (eg/immunoglobulin and apolipoprotein), and improved knee functional status. SF appeared to become less susceptible to degeneration after aPRP injections in group 2. As a result, at least 2 monthly injection of IA aPRP in conjunction with accurate injection of aPRP to the perimeniscal soft tissue structure such as the pes anserinus may be a viable option in treating patients with moderate to severe degrees of knee OA.
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Li Y, Fu SC, Cheuk YC, Song G, Feng H, Yung SH. The non-reconstructive treatment of complete ACL tear with biological enhancement in clinical and preclinical studies: A systematic review. Asia Pac J Sports Med Arthrosc Rehabil Technol 2018; 14:10-16. [PMID: 30302314 PMCID: PMC6170796 DOI: 10.1016/j.asmart.2018.04.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Revised: 03/28/2018] [Accepted: 04/09/2018] [Indexed: 01/15/2023] Open
Abstract
Introduction There is still controversy regarding the bio-enhanced non-reconstructive ACL treatment. Materials and methods A search for articles in databases was performed in February 2017. The objective and subjective evaluations of clinical studies and biomechanical and histological data of preclinical studies were extracted. Results Eighteen articles were included for analysis. In clinical studies, although subjective scores were significantly improved, the rate of re-operation rate was high. In preclinical studies, bio-enhancing techniques demonstrated promotion of the healing of ACL. Conclusions The efficacy of biological enhancement cannot be validated in clinical studies. Preclinical studies showed improved biomechanical and healing potential.
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Affiliation(s)
- Yue Li
- Sports Medicine Service, Beijing Jishuitan Hospital, China
| | - Sai Cheun Fu
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, China.,Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Yau Chuk Cheuk
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, China.,Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Guanyang Song
- Sports Medicine Service, Beijing Jishuitan Hospital, China
| | - Hua Feng
- Sports Medicine Service, Beijing Jishuitan Hospital, China
| | - Shu-Hang Yung
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, China.,Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Hong Kong, China
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Huard J, Bolia I, Briggs K, Utsunomiya H, Lowe WR, Philippon MJ. Potential Usefulness of Losartan as an Antifibrotic Agent and Adjunct to Platelet-Rich Plasma Therapy to Improve Muscle Healing and Cartilage Repair and Prevent Adhesion Formation. Orthopedics 2018; 41:e591-e597. [PMID: 30092110 DOI: 10.3928/01477447-20180806-05] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Accepted: 10/23/2017] [Indexed: 02/03/2023]
Abstract
Postoperative tissue fibrosis represents a major complication in orthopedics. Transforming growth factor beta 1 is a key molecule in the development of postoperative fibrosis. High concentrations of transforming growth factor beta 1 have also been implicated in various diseases. Agents that counteract the actions of transforming growth factor beta 1 have been investigated as potential antifibrotic medications and as adjunct treatment to platelet-rich plasma injections (increased amounts of transforming growth factor beta 1) to improve their effectiveness and/or safety profile. Losartan blocks transforming growth factor beta 1 action and has attracted special interest in orthopedic research that focuses on how to reduce the risk of postoperative fibrosis. [Orthopedics. 2018; 41(5):e591-e597.].
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Partial Anterior Cruciate Ligament Ruptures: Advantages by Intraligament Autologous Conditioned Plasma Injection and Healing Response Technique-Midterm Outcome Evaluation. BIOMED RESEARCH INTERNATIONAL 2018; 2018:3204869. [PMID: 30148163 PMCID: PMC6083554 DOI: 10.1155/2018/3204869] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Accepted: 07/02/2018] [Indexed: 02/06/2023]
Abstract
The historical treatment options for partial anterior cruciate ligament (ACL) ruptures were conservative therapy or ACL reconstruction by injured bundle or entire ACL replacement. In awareness of the regenerative potential of biologic agents such as mesenchymal stem cells or platelet rich plasma (PRP), the healing response technique was developed to preserve the injured ACL with better outcomes than the conservative therapy. Further improvement of this technique seems to be obtained by the additional application of PRP products. Thus, the aim of this study was to evaluate the midterm outcome after intraligament autologous conditioned plasma (ACP) by a clinical, scoring, and functional performance assessment. 42 patients were evaluated in this study. The failure rate was 9.5%. Outcome evaluation showed good to excellent results. The scores were IKDC subjective 83.2 (SD 14.5), Lysholm 85.5 (SD 15.5), Tegner 4.7 (SD 1.7), and Cincinnati 85.4 (SD 15.5) after a mean follow-up of 33 months. Clinical examination showed stable Lachman test, negative pivot shift phenomenon, and a significant reduction in AP-laxity compared to preoperative status (rolimeter preoperative: 1.9 (SD1.4); postoperative 0.6 (SD1.8), p=0.001) in all patients. Functional performance testing showed no significant differences between the injured and healthy side. Return to sport was achieved after a mean of 5.8 months (SD 3.6) in 71.1% of the included patients. In summary, this new treatment option revealed in midterm follow-up promising results to treat partial ACL lesions with a reduced need for conversion to ACL reconstruction and with a high percentage of return to preinjury sport activity.
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Walters BL, Porter DA, Hobart SJ, Bedford BB, Hogan DE, McHugh MM, Klein DA, Harousseau K, Nicholas SJ. Effect of Intraoperative Platelet-Rich Plasma Treatment on Postoperative Donor Site Knee Pain in Patellar Tendon Autograft Anterior Cruciate Ligament Reconstruction: A Double-Blind Randomized Controlled Trial. Am J Sports Med 2018; 46:1827-1835. [PMID: 29741923 DOI: 10.1177/0363546518769295] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Donor site morbidity in the form of anterior knee pain is a frequent complication after bone-patellar tendon-bone (BPTB) autograft anterior cruciate ligament (ACL) reconstruction. Hypothesis/Purpose: The purpose was to examine the effect of the intraoperative administration of platelet-rich plasma (PRP) on postoperative kneeling pain. It was hypothesized that PRP treatment would reduce knee pain. STUDY DESIGN Randomized controlled trial; Level of evidence, 2. METHODS Fifty patients (mean ± SD age, 30 ± 12 years) undergoing BPTB ACL autograft reconstruction were randomized to the PRP (n = 27) or sham (n = 23) treatment. In either case, 10 mL of venous blood was drawn before the induction of anesthesia and either discarded (sham) or processed (PRP) for preparation of a PRP gel to be later mixed with donor site bone chips and inserted into the patellar defect. At 12 weeks, 6 months, 1 year, and 2 years after surgery, patients completed International Knee Documentation Committee (IKDC) forms and visual analog scale pain scores for activities of daily living and kneeling. Healing indices at the donor site were assessed by routine noncontrast magnetic resonance imaging (MRI) at 6 months. Mixed-model analysis of variance was used to assess the effect of PRP on patient symptoms and MRI indices of donor site healing, as measured by the width of the donor site defect. RESULTS Kneeling pain, pain with activities of daily living, and IKDC scores were not different between treatment groups at any of the time intervals ( P = .08-.83). Kneeling pain improved from 12 weeks to 6 months and from 1 to 2 years ( P < .05). IKDC scores improved substantially from 12 weeks to 6 months ( P < .001) and continued to improve to 2 years (PRP, 86 ± 19; sham, 89 ± 10). MRI indices of donor site healing were not different between treatment groups ( P = .53-.90). CONCLUSION Whether randomized to receive PRP in their patellar defect or not, patients continued to have similar levels of kneeling pain and patellar defect sizes after autograft BPTB ACL reconstruction. Registration: NCT01765712 ( ClinicalTrials.gov identifier).
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Affiliation(s)
- Brian L Walters
- Sports Medicine Division, Department of Orthopaedic Surgery, Lenox Hill Hospital, New York, New York, USA
| | - David A Porter
- Sports Medicine Division, Department of Orthopaedic Surgery, Lenox Hill Hospital, New York, New York, USA
| | - Sarah J Hobart
- Sports Medicine Division, Department of Orthopaedic Surgery, Lenox Hill Hospital, New York, New York, USA
| | - Benjamin B Bedford
- Sports Medicine Division, Department of Orthopaedic Surgery, Lenox Hill Hospital, New York, New York, USA
| | - Daniel E Hogan
- Nicholas Institute of Sports Medicine and Athletic Trauma, New York, New York, USA
| | - Malachy M McHugh
- Nicholas Institute of Sports Medicine and Athletic Trauma, New York, New York, USA
| | - Devon A Klein
- Department of Radiology, Lenox Hill Hospital, Northwell Health, New York, New York, USA
| | - Kendall Harousseau
- Nicholas Institute of Sports Medicine and Athletic Trauma, New York, New York, USA
| | - Stephen J Nicholas
- Sports Medicine Division, Department of Orthopaedic Surgery, Lenox Hill Hospital, New York, New York, USA
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20
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van Eck CF, Limpisvasti O, ElAttrache NS. Is There a Role for Internal Bracing and Repair of the Anterior Cruciate Ligament? A Systematic Literature Review. Am J Sports Med 2018; 46:2291-2298. [PMID: 28783472 DOI: 10.1177/0363546517717956] [Citation(s) in RCA: 99] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Renewed interest has arisen in arthroscopic anterior cruciate ligament (ACL) repair techniques. HYPOTHESIS ACL repair with or without some form of internal bracing could lead to good outcomes in a carefully selected subset of patients. STUDY DESIGN Systematic review. METHODS An electronic database search was performed to identify 89 papers describing preclinical and clinical studies on the outcome of ACL repair. RESULTS Proximal ACL tear patterns showed a better healing potential with primary repair than distal or midsubstance tears. Some form of internal bracing increased the success rate of ACL repair. Improvement in the biological characteristics of the repair was obtained by bone marrow access by drilling tunnels or microfracture. Augmentation with platelet-rich plasma was beneficial only in combination with a structural scaffold. Skeletally immature patients had the best outcomes. Acute repair offered improved outcomes with regard to load, stiffness, laxity, and rerupture. CONCLUSION ACL repair may be a viable option in young patients with acute, proximal ACL tears. The use of internal bracing, biological augmentation, and scaffold tissue may increase the success rate of repair.
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Affiliation(s)
| | - Orr Limpisvasti
- Kerlan Jobe Orthopaedic Clinic, Los Angeles, California, USA
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21
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Koch M, Matteo BD, Eichhorn J, Zellner J, Mayr F, Krutsch W, Achenbach L, Woehl R, Nerlich M, Angele P. Intra-ligamentary autologous conditioned plasma and healing response to treat partial ACL ruptures. Arch Orthop Trauma Surg 2018; 138:675-683. [PMID: 29383441 DOI: 10.1007/s00402-018-2885-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Indexed: 01/09/2023]
Abstract
INTRODUCTION Conservative treatment of partial ACL ruptures is associated with a high failure rate, and often patients undergo ACL reconstruction. ACL preservation by trephination of the ACL origin and application of Autologous Conditioned Plasma (ACP) seems to be an intriguing new treatment option to favour ACL tissue healing and avoid traditional reconstruction. The aim of this study was to describe the mid-term outcomes of this new ACL preserving technique. MATERIALS AND METHODS Twenty-four patients (mean age 41.8 years) affected by partial rupture of one or both ACL bundles were included in the present trial. The partial ACL tears were arthroscopically assessed and classified according to a new five step grading system. All patients were treated by trephination of the femoral ACL stump and intra-ligamentary application of ACP. The postoperative outcome was evaluated by both subjective scores and stability testing up to a mean of 25.1 months' follow-up. Adverse events and failure rate were also documented. RESULTS Clinical outcome was good to excellent with IKDC subjective 82.7 (SD 11.8), Lysholm 87.6 (SD 8.1), Tegner 5.3 (SD 2.1), Cincinnati 88.7 (SD 14.8). The failure rate (i.e. persisting knee instability assessed clinically or by rolimeter) was 12.5%. At objective measurements, knee joints showed a firm endpoint in Lachman test, negative pivot shift phenomenon and a significant reduction in AP-laxity compared to pre-operative status by rolimeter testing (p = 0.002). Return to sport practice was achieved after mean 4.8 months (SD 4.1). CONCLUSIONS ACL stump trephination and concomitant intra-ligamentary application of ACP revealed promising results at mid-term follow-up to treat partial ACL lesions.
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Affiliation(s)
- Matthias Koch
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz Josef Strauss Allee 11, 93042, Regensburg, Germany
| | - Berardo Di Matteo
- Center for Biological and Functional Reconstruction of the Knee, Humanitas Research and University Hospital, Rozzano, Italy
| | - Jürgen Eichhorn
- Sporthopaedicum Straubing, Regensburg, Hildegard von Bingen Strasse 1, 93053, Regensburg, Germany
| | - Johannes Zellner
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz Josef Strauss Allee 11, 93042, Regensburg, Germany
| | - Felix Mayr
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz Josef Strauss Allee 11, 93042, Regensburg, Germany
| | - Werner Krutsch
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz Josef Strauss Allee 11, 93042, Regensburg, Germany
| | - Leonard Achenbach
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz Josef Strauss Allee 11, 93042, Regensburg, Germany
| | - Rebecca Woehl
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz Josef Strauss Allee 11, 93042, Regensburg, Germany
| | - Michael Nerlich
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz Josef Strauss Allee 11, 93042, Regensburg, Germany
| | - Peter Angele
- Department of Trauma Surgery, University Medical Centre Regensburg, Franz Josef Strauss Allee 11, 93042, Regensburg, Germany. .,Sporthopaedicum Straubing, Regensburg, Hildegard von Bingen Strasse 1, 93053, Regensburg, Germany.
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LaPrade RF, Goodrich LR, Phillips J, Dornan GJ, Turnbull TL, Hawes ML, Dahl KD, Coggins AN, Kisiday J, Frisbie D, Chahla J. Use of Platelet-Rich Plasma Immediately After an Injury Did Not Improve Ligament Healing, and Increasing Platelet Concentrations Was Detrimental in an In Vivo Animal Model. Am J Sports Med 2018; 46:702-712. [PMID: 29211969 DOI: 10.1177/0363546517741135] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Limited information in basic science and clinical trials exists to determine if ligament healing may be accelerated with the use of biological adjuvants, such as platelet-rich plasma (PRP). However, there has been widespread acceptance of PRP for use in clinical practice, despite an inadequate understanding of its biological mechanism of action. PURPOSE To determine whether a single dose of PRP could accelerate ligament healing and correspondingly improve histological characteristics and biomechanical properties when injected immediately postoperatively into the injured medial collateral ligament (MCL) of New Zealand White rabbits. STUDY DESIGN Controlled laboratory study. METHODS Eighty skeletally mature New Zealand White rabbits (160 knees) were used. The MCL was torn midbody to simulate a grade 3 tear. After an acute injury of the MCL, the administration of autologous PRP at 3 different platelet concentrations (0 million/uL, platelet-poor plasma [PPP]; 0.6 million/uL, 2 times the baseline [2× PRP]; and 1.2 million/uL, 4 times the baseline [4× PRP]) was performed and compared with a saline injection control in the contralateral knee. Histological analysis and a biomechanical endpoint characterization were utilized to assess ligamentous healing and compare it to a sham surgery group. RESULTS The PPP ( P = .001) and 4× PRP ( P = .002) groups had a significantly lower collagen subscore than the sham surgery group. No other differences were observed among the treatment groups, including the vascularity subscore and overall ligament tissue maturity index score. Compared with saline-injected contralateral knees, the maximum load for PPP and 2× PRP was not significantly different ( P = .788 and .325, respectively). The maximum load and stiffness for knees treated with 4× PRP were significantly less than for the saline-treated contralateral knees ( P = .006 and .001, respectively). CONCLUSION One single dose of PPP or 2× PRP at the time of injury did not improve ligament healing. In addition, 4× PRP negatively affected ligament strength and histological characteristics at 6 weeks after the injury. CLINICAL RELEVANCE The current practice of treating knee ligament injuries with PRP may not improve healing at low doses of PRP. The decreased mechanical properties and histological appearance of the torn MCL suggest that high doses of PRP decrease the quality of repair tissue. Further in vivo studies are necessary to determine the dosing and timing of PRP administration after a ligament injury before the widespread use of PRP to treat ligament injuries is recommended.
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Affiliation(s)
- Robert F LaPrade
- Steadman Philippon Research Institute, Vail, Colorado, USA.,The Steadman Clinic, Vail, Colorado, USA
| | - Laurie R Goodrich
- Orthopaedic Research Center, Colorado State University, Fort Collins, Colorado, USA
| | - Jennifer Phillips
- Orthopaedic Research Center, Colorado State University, Fort Collins, Colorado, USA
| | - Grant J Dornan
- Steadman Philippon Research Institute, Vail, Colorado, USA
| | | | | | - Kimi D Dahl
- Steadman Philippon Research Institute, Vail, Colorado, USA
| | | | - John Kisiday
- Orthopaedic Research Center, Colorado State University, Fort Collins, Colorado, USA
| | - David Frisbie
- Orthopaedic Research Center, Colorado State University, Fort Collins, Colorado, USA
| | - Jorge Chahla
- Steadman Philippon Research Institute, Vail, Colorado, USA
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Perrone GS, Proffen BL, Kiapour AM, Sieker JT, Fleming BC, Murray MM. Bench-to-bedside: Bridge-enhanced anterior cruciate ligament repair. J Orthop Res 2017; 35:2606-2612. [PMID: 28608618 PMCID: PMC5729057 DOI: 10.1002/jor.23632] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2017] [Accepted: 06/05/2017] [Indexed: 02/04/2023]
Abstract
Anterior cruciate ligament (ACL) injuries are one of the most well-known orthopaedic injuries and are treated with one of the most common orthopaedic procedures performed in the United States. This surgical procedure, ACL reconstruction, is successful at restoring the gross stability of the knee. However, the outcomes of ACL reconstruction can be limited by short and long-term complications, including muscle weakness, graft rupture, and premature osteoarthritis. Thus, new methods of treating this injury are being explored. This review details the pathway of how a tissue engineering strategy can be used to improve the healing of the ACL in preclinical studies and then translated to patients in an FDA-approved clinical study. This review paper will outline the clinical importance of ACL injuries, history of primary repair, the pathology behind failure of the ACL to heal, pre-clinical studies, the FDA approval process for a high risk medical device, and the preliminary results from a first-in-human study. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2606-2612, 2017.
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Affiliation(s)
- Gabriel S Perrone
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Harvard Medical School/Boston Children's Hospital, Boston, Massachusetts
| | - Benedikt L Proffen
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Harvard Medical School/Boston Children's Hospital, Boston, Massachusetts
| | - Ata M Kiapour
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Harvard Medical School/Boston Children's Hospital, Boston, Massachusetts
| | - Jakob T Sieker
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Harvard Medical School/Boston Children's Hospital, Boston, Massachusetts
| | - Braden C Fleming
- Department of Orthopaedics, Bioengineering Labs, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island
| | - Martha M Murray
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Harvard Medical School/Boston Children's Hospital, Boston, Massachusetts
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You T, Bai L, Zhang X, Li W, Jiang C, Zhang W. [Short-term effectiveness of absorbable anchor in repairing of partial anterior cruciate ligament rupture]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2017; 31:1190-1194. [PMID: 29806319 DOI: 10.7507/1002-1892.201610026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Objective To study the short-term effectiveness of absorbable anchor in repairing of partial anterior cruciate ligament (ACL) rupture. Methods Between December 2013 and February 2015, 22 patients with partial ACL rupture were repaired with absorbable anchor under arthroscopy. There were 12 males and 10 females with an average age of 27.5 years (range, 20-44 years). The injury located at left knee in 8 cases and at right knee in 14 cases. The time from injury to admission ranged from 2 to 13 days (mean, 9.8 days). Sixteen partial ACL ruptures combined with meniscus injury. The effectiveness was assessed by Tegner score, Lysholm score, International Knee Documentation Committee (IKDC) score, visual analogue scale (VAS) score, and MRI, as well as knee laxity was evaluated by KT-1000. Results All incisions healed at stage Ⅰ without any complication. All patients were followed up 12 months. ACL rerupture did not occurred during follow-up. There was no significant difference in Tegner score, Lysholm score, and IKDC score between before injury and at 12 months after operation ( P>0.05). And the median satisfaction VAS score was 9.5 (range, 9-10). The tibial anterior translation difference was 0.5 mm (range, 0-6 mm). MRI showed that the scarring and continuity of the ligament were rated as grade 1 in all patients. Conclusion Arthroscopic repairing by absorbable anchor is a feasible method for partial ACL rupture, with ideal knee function, good satisfaction, and satisfactory short-term effectiveness.
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Affiliation(s)
- Tian You
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen Guangdong, 518036, P.R.China
| | - Lu Bai
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen Guangdong, 518036, P.R.China
| | - Xintao Zhang
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen Guangdong, 518036, P.R.China
| | - Wei Li
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen Guangdong, 518036, P.R.China
| | - Changqing Jiang
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen Guangdong, 518036, P.R.China
| | - Wentao Zhang
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen Guangdong, 518036,
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25
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Evangelopoulos DS, Kohl S, Schwienbacher S, Gantenbein B, Exadaktylos A, Ahmad SS. Collagen application reduces complication rates of mid-substance ACL tears treated with dynamic intraligamentary stabilization. Knee Surg Sports Traumatol Arthrosc 2017; 25:2414-2419. [PMID: 26564213 DOI: 10.1007/s00167-015-3838-7] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2015] [Accepted: 10/22/2015] [Indexed: 01/22/2023]
Abstract
PURPOSE Dynamic intraligamentary stabilization was recently proposed as an option for the treatment of acute ACL ruptures. The aim of this study was to investigate the feasibility of the procedure in mid-substance ACL ruptures and examine whether the additional application of a bilayer collagen I/III membrane would provide for a superior outcome. METHODS The study group consisted of patients presenting with a mid-substance ACL rupture undergoing dynamic intraligamentary stabilization using the Ligamys™ device along with application of a collagen I/III membrane to the surface of the ACL (group A, n = 23). The control group comprised a matched series of patients presenting with a mid-substance ACL rupture also treated by dynamic intraligamentary stabilization Ligamys™ repair, however, without additional collagen application (group B, n = 33). Patients were evaluated preoperatively and at 24-month follow-up for stability as well as Tegner and Lysholm scores. Knee laxity was measured as a difference in anterior translation (ΔAP) and pivot shift. Any events occurring during the follow-up period of 24 months were documented. Logistic regression of complications was performed, and adjustment undertaken where necessary. RESULTS A high total complication rate of 78.8 % was noted in group B, compared to group A (8.7 %) (p = 0.002). The addition of a collagen membrane was the only independent prognostic factor associated with reduced complications (OR 8.0, CI 2.0-32.2, p = 0.003, for collagen-free treatment). In group B, 6 patients suffered a re-rupture with subsequent instability requiring secondary hamstring reconstruction surgery, and 11 developed extension loss requiring arthroscopic debridement, whilst in group A, 2 patients required arthroscopic debridement for loss of exension, with no further encountered complication. Median Lysholm score was significantly higher in group A compared to group B (median 100 range 93-100 vs median 95 range 60-100, p = 0.03) at final follow-up. CONCLUSIONS A high complication rate following ACL Ligamys™ repair of mid-substance ruptures was noted. Application of a collagen membrane to the surface of the ACL resulted in a reduced incidence of extension deficit and re-ruptures. The results indicate that solitary ACL Ligamys™ repair does not present an appropriate treatment modality for mid-substance ACL ruptures. Collage application proved to provide healing benefits with superior clinical outcome after ACL repair. LEVEL OF EVIDENCE Case control study, Level III.
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Affiliation(s)
| | - Sandro Kohl
- Department of Orthopaedic Surgery and Traumatology, Inselspital, University of Bern, Bern, Switzerland.
| | - Stefan Schwienbacher
- Department of Orthopaedic Surgery and Traumatology, Inselspital, University of Bern, Bern, Switzerland
| | - Benjamin Gantenbein
- Institute for Surgical Technology and Biomechanics (ISTB), University of Bern, Bern, Switzerland
| | | | - Sufian S Ahmad
- Department of Orthopaedic Surgery and Traumatology, Inselspital, University of Bern, Bern, Switzerland.,Institute for Surgical Technology and Biomechanics (ISTB), University of Bern, Bern, Switzerland
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Hauschild G, Geburek F, Gosheger G, Eveslage M, Serrano D, Streitbürger A, Johannlükens S, Menzel D, Mischke R. Short term storage stability at room temperature of two different platelet-rich plasma preparations from equine donors and potential impact on growth factor concentrations. BMC Vet Res 2017; 13:7. [PMID: 28056978 PMCID: PMC5216599 DOI: 10.1186/s12917-016-0920-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2016] [Accepted: 12/09/2016] [Indexed: 11/14/2022] Open
Abstract
Background The increasing interest in platelet-rich plasma (PRP) based therapies is as yet accompanied by inconsistent information regarding nearly all aspects of handling and application. Among these storage stability of processed platelet-rich products may be the basis for a more flexible application mode. The objective of this study was (1) to estimate the storage stability of growth factors platelet derived growth factor BB (PDGF-BB) and transforming growth factor ß1 (TGF-ß1) in both, a single-step softspin centrifugation-based pure-PRP (P-PRP, ACP®), and a gravity filtration system-based leukocyte-rich-PRP (L-PRP, E-PET), over a six hours time span after preparation at room temperature and (2) to identify possible factors influencing these growth factor concentrations in an equine model. Results Growth factor concentrations remained stable over the entire investigation period in L-PRP as well as P-PRP preparations revealing a mean of 3569 pg/ml PDGF-BB for E-PET and means of 1276 pg/ml PDGF-BB and 5086 pg/ml TGF-ß1 for ACP®. Pearson correlations yielded no significant impact of whole blood platelet (PLT), white blood cell (WBC) and red blood cell (RBC) counts on resulting cytokine values. In case of ACP® no significant dependencies between PLT, WBC and RBC counts of the processed platelet-rich product and resulting cytokine content occurred with exception of TGF-ß1 concentrations showing a strong correlation with the WBC content. PDGF-BB content of E-PET preparations showed a strong positive correlation with PLT and a strong negative with WBC of these preparations but not with RBC. Conclusions L-PRP ad modum E-PET and P-PRP ad modum ACP® are applicable over at least a six hours time span at room temperature without loss of growth factor content. Based on the results of this study factors influencing the resulting growth factor concentrations still remain questionable. Additional studies implicating a further standardization of preparation protocols are necessary to identify consistent impact on cytokine content after PRP processing. Electronic supplementary material The online version of this article (doi:10.1186/s12917-016-0920-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Gregor Hauschild
- Department of Orthopedics and Tumororthopedics, University Hospital of Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany.
| | - Florian Geburek
- Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hanover, Germany
| | - Georg Gosheger
- Department of Orthopedics and Tumororthopedics, University Hospital of Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany
| | - Maria Eveslage
- Institute of Biostatistics and Clinical Research, University of Muenster (WWU), Schmeddingstraße 56, 48149, Münster, Germany
| | - Daniela Serrano
- Department of Orthopedics and Tumororthopedics, University Hospital of Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany
| | - Arne Streitbürger
- Department of Orthopedics and Tumororthopedics, University Hospital of Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany
| | - Sara Johannlükens
- Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hanover, Germany
| | - Dirk Menzel
- Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hannover, Germany
| | - Reinhard Mischke
- Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hannover, Germany
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Yung YL, Fu SC, Cheuk YC, Qin L, Ong MTY, Chan KM, Yung PSH. Optimisation of platelet concentrates therapy: Composition, localisation, and duration of action. Asia Pac J Sports Med Arthrosc Rehabil Technol 2017; 7:27-36. [PMID: 29264271 PMCID: PMC5721920 DOI: 10.1016/j.asmart.2016.11.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Revised: 11/06/2016] [Accepted: 11/29/2016] [Indexed: 12/18/2022] Open
Abstract
Platelet concentrates (PC) generally refers to a group of products that are prepared from autologous blood intended to enhance healing activities. PC therapy is now very popular in treating musculoskeletal injuries; however, inconsistent clinical results urge the need to understand the working mechanism of PC. It is generally believed that the platelet-derived bioactive factors are the active constituents, and their bioavailability in the vicinity of the lesion sites determines the treatment efficacies. Therefore, the composition, localisation, and duration of the action of PC would be key determinants. In this review, we discuss how different preparations and delivery methods of PC would affect the treatment outcomes with respect to clinical evidence about PC therapy for osteoarthritis, tendinopathies, rotator cuff tears, anterior cruciate ligament injuries, and bone fractures. This review can be used as a quick guide for the use of PC therapy and provide insights for the further optimisation of the therapy in the near future.
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Affiliation(s)
- Yuk-Lin Yung
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
- Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Sai-Chuen Fu
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
- Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Yau-Chuk Cheuk
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
- Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Ling Qin
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
- Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Michael Tim-Yun Ong
- Department of Orthopaedics and Traumatology, Alice Ho Miu Ling Nethersole Hospital, Hong Kong Special Administrative Region
| | - Kai-Ming Chan
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
- Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Patrick Shu-Hang Yung
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
- Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
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Murray MM, Flutie BM, Kalish LA, Ecklund K, Fleming BC, Proffen BL, Micheli LJ. The Bridge-Enhanced Anterior Cruciate Ligament Repair (BEAR) Procedure: An Early Feasibility Cohort Study. Orthop J Sports Med 2016; 4:2325967116672176. [PMID: 27900338 PMCID: PMC5120682 DOI: 10.1177/2325967116672176] [Citation(s) in RCA: 110] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background: This study assessed the safety of the newly developed bridge-enhanced anterior cruciate ligament (ACL) repair (BEAR), which involves suture repair of the ligament combined with a bioactive scaffold to bridge the gap between the torn ligament ends. As the intra-articular environment is complex in its response to implanted materials, this study was designed to determine whether there would be a significant rate of adverse reaction to the implanted scaffold. Hypothesis: The primary hypothesis was that the implanted scaffold would not result in a deep joint infection (arthrocentesis with positive culture) or significant inflammation (clinical symptoms justifying arthrocentesis but negative culture). The secondary hypotheses were that patients treated with BEAR would have early postoperative outcomes that were similar to patients treated with ACL reconstruction with an autologous hamstring graft. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 20 patients were enrolled in this nonrandomized, first-in-human study. Ten patients received BEAR treatment and 10 received a hamstring autograft ACL reconstruction. The BEAR procedure was performed by augmenting a suture repair with a proprietary scaffold, the BEAR scaffold, placed in between the torn ends of the ACL at the time of suture repair. The BEAR scaffold is to our knowledge the only device that fills the gap between the torn ligament ends to have current Investigational Device Exemption approval from the Food and Drug Administration. Ten milliliters of autologous whole blood were added to the scaffold prior to wound closure. Outcomes were assessed at 3 months postoperatively. The outcomes measures included postoperative pain, muscle atrophy, loss of joint range of motion, and implant failure (designated by an International Knee Documentation Committee grade C or D Lachman test and/or an absence of continuous ACL tissue on magnetic resonance images). Results: There were no joint infections or signs of significant inflammation in either group. There were no differences between groups in effusion or pain, and no failures by Lachman examination criteria (BEAR, 8 grade A and 2 grade B; ACL reconstruction, 10 grade A). Magnetic resonance images from all of the BEAR and ACL-reconstructed patients demonstrated a continuous ACL or intact graft. In addition, hamstring strength at 3 months was significantly better in the BEAR group than in the hamstring autograft group (mean ± SD: 77.9% ± 14.6% vs 55.9% ± 7.8% of the contralateral side; P < .001). Conclusion: The results of this study suggest that the BEAR procedure may have a rate of adverse reactions low enough to warrant a study of efficacy in a larger group of patients.
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Affiliation(s)
- Martha M Murray
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital Boston, Massachusetts, USA
| | - Brett M Flutie
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital Boston, Massachusetts, USA
| | - Leslie A Kalish
- Clinical Research Center, Boston Children's Hospital Boston, Massachusetts, USA
| | - Kirsten Ecklund
- Department of Radiology, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Braden C Fleming
- Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island, USA
| | - Benedikt L Proffen
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital Boston, Massachusetts, USA
| | - Lyle J Micheli
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital Boston, Massachusetts, USA
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29
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Di Matteo B, Loibl M, Andriolo L, Filardo G, Zellner J, Koch M, Angele P. Biologic agents for anterior cruciate ligament healing: A systematic review. World J Orthop 2016; 7:592-603. [PMID: 27672573 PMCID: PMC5027015 DOI: 10.5312/wjo.v7.i9.592] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Revised: 06/22/2016] [Accepted: 07/18/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To systematically review the currently available literature concerning the application of biologic agents such as platelet-rich plasma (PRP) and stem cells to promote anterior cruciate ligament (ACL) healing.
METHODS A systematic review of the literature was performed on the use of biologic agents (i.e., PRP or stem cells) to favor ACL healing during reconstruction or repair. The following inclusion criteria for relevant articles were used: Clinical reports of any level of evidence, written in English language, on the use of PRP or stem cells during ACL reconstruction/repair. Exclusion criteria were articles written in other languages, reviews, or studies analyzing other applications of PRP/stem cells in knee surgery not related to promoting ACL healing.
RESULTS The database search identified 394 records that were screened. A total of 23 studies were included in the final analysis: In one paper stem cells were applied for ACL healing, in one paper there was a concomitant application of PRP and stem cells, whereas in the remaining 21 papers PRP was used. Based on the ACL injury pattern, two papers investigated biologic agents in ACL partial tears whereas 21 papers in ACL reconstruction. Looking at the quality of the available literature, 17 out of 21 studies dealing with ACL reconstruction were randomized controlled trials. Both studies on ACL repair were case series.
CONCLUSION There is a paucity of clinical trials investigating the role of stem cells in promoting ACL healing both in case of partial and complete tears. The role of PRP is still controversial and the only advantage emerging from the literature is related to a better graft maturation over time, without documenting beneficial effects in terms of clinical outcome, bone-graft integration and prevention of bony tunnel enlargement.
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30
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Vavken P, Sadoghi P, Palmer M, Rosso C, Mueller AM, Szoelloesy G, Valderrabano V. Platelet-Rich Plasma Reduces Retear Rates After Arthroscopic Repair of Small- and Medium-Sized Rotator Cuff Tears but Is Not Cost-Effective. Am J Sports Med 2015; 43:3071-6. [PMID: 25767267 DOI: 10.1177/0363546515572777] [Citation(s) in RCA: 84] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND It has been suggested that platelet-rich plasma (PRP) improves healing after arthroscopic rotator cuff repair. The current literature provides ample but inconsistent data on this topic. PURPOSE To systematically review the current in vivo evidence for the use of platelet concentrates (PRP) in the arthroscopic treatment of rotator cuff tears to assess effectiveness, safety, and cost-effectiveness. STUDY DESIGN Meta-analysis and cost-effectiveness analysis. METHODS Published evidence from controlled, human trials of rotator cuff repair augmented with platelet concentrates was systematically gathered, and data on retear rates were extracted. Mathematical and clinical heterogeneity was evaluated, and fixed-effect meta-analysis was performed to calculate the risk ratio (RR) of retears and the number needed to treat (NNT). Subgroup analyses were made for small/medium tears (n = 404) and large/massive tears (n = 374). Cost-effectiveness was assessed using data from this meta-analysis and using cost data from the literature, including extensive sensitivity analyses, to calculate the incremental cost-effectiveness ratio (ICER). RESULTS Thirteen studies published between 2010 and 2014 were identified for analysis. The RR for retear for all patients was 0.87 (95% CI, 0.67-1.12; P = .286). For small- and medium-sized tears (<3 cm), the RR for retear was 0.60 (95% CI, 0.37-0.97), consistent with a significant difference in favor of PRP use (P = .038). This translated into an NNT of 14 (95% CI, 7-125). However, at an ICER of US$127,893 per quality-adjusted life year gained, assuming a 5% revision rate, the use of PRP was not cost-effective for small- and medium-sized tears. CONCLUSION In large tears, even with double-row repair, the beneficial effects of PRP alone are insufficient to compensate the progressed tissue damage. The study data suggest that PRP may promote healing of small- and medium-sized tears to reduce retear rates. However, despite the substantial biological effect, at current cost, the use of PRP is not cost-effective in arthroscopic repair of small- and medium-sized tears.
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Affiliation(s)
- Patrick Vavken
- Division of Sports Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA Harvard Center for Population and Development Studies, Harvard School of Public Health, Boston, Massachusetts, USA Department of Orthopaedic Surgery, University Hospital Basel, Basel, Switzerland
| | - Patrick Sadoghi
- Department of Orthopaedic Surgery, Medical University Graz, Graz, Austria
| | | | - Claudio Rosso
- Department of Orthopaedic Surgery, University Hospital Basel, Basel, Switzerland ALTIUS Swiss Sportmed Center, Basel, Switzerland
| | - Andreas M Mueller
- Department of Orthopaedic Surgery, University Hospital Basel, Basel, Switzerland
| | - Gregor Szoelloesy
- Department of Orthopaedic Surgery, University Hospital Basel, Basel, Switzerland
| | - Victor Valderrabano
- Department of Orthopaedic Surgery, University Hospital Basel, Basel, Switzerland
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31
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Taylor SA, Khair MM, Roberts TR, DiFelice GS. Primary Repair of the Anterior Cruciate Ligament: A Systematic Review. Arthroscopy 2015; 31:2233-47. [PMID: 26165465 DOI: 10.1016/j.arthro.2015.05.007] [Citation(s) in RCA: 96] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2014] [Revised: 04/13/2015] [Accepted: 05/13/2015] [Indexed: 02/02/2023]
Abstract
PURPOSE To describe the clinical and preclinical research conducted on primary repair of the anterior cruciate ligament (ACL) during the past 10 years. METHODS A systematic search of PubMed, the Cochrane Central Register of Controlled Trials, and Embase was performed for all English-language studies published between 2003 and April 2014 on primary repair of the ACL. RESULTS Twenty-six studies met the inclusion and exclusion criteria. In the clinical research group, 8 studies (166 patients; age range, 10 to 71 years) met the inclusion and exclusion criteria and were largely long-term clinical outcome studies, based on the original cohorts from the 1970s and 1980s, and suggested high failure rates, additional surgery, and revision for instability. A subset of patients, however, achieved good to excellent subjective and objective long-term outcomes. In the preclinical research group, 18 studies met the inclusion and exclusion criteria and were based on an ACL transection model; they suggested that (1) stabilization of the knee with an internal suture strut improved the healing and biomechanical properties of the repaired ACL, (2) "enhancing" the repair with biological collagen-platelet composite augmentation improved healing and mechanical strength, (3) younger age and skeletal immaturity seem to correlate with improved histologic healing and biomechanical properties, (4) enhanced primary repair of the ACL may reduce post-traumatic osteoarthritis, and (5) the native ACL biomechanically outperformed the repaired ACL. CONCLUSIONS Although long-term human studies suggest collectively unacceptable outcomes for open primary repair of the ACL, a subset of patients achieved acceptable long-term results. ACL transection model animal studies showed improved healing and biomechanics with primary suture repair stabilization, early intervention, biological augmentation techniques, and younger age. Primary repair of the ACL may be an effective treatment modality for an appropriately selected subset of patients. LEVEL OF EVIDENCE Level IV, systematic review of preclinical and clinical Level IV studies.
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Affiliation(s)
- Samuel A Taylor
- Orthopaedic Trauma and Sports Medicine Services, Hospital for Special Surgery, New York, New York, U.S.A
| | - M Michael Khair
- Orthopaedic Trauma and Sports Medicine Services, Hospital for Special Surgery, New York, New York, U.S.A
| | - Timothy R Roberts
- Orthopaedic Trauma and Sports Medicine Services, Hospital for Special Surgery, New York, New York, U.S.A
| | - Gregory S DiFelice
- Orthopaedic Trauma and Sports Medicine Services, Hospital for Special Surgery, New York, New York, U.S.A..
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32
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Proffen BL, Perrone GS, Fleming BC, Sieker JT, Kramer J, Hawes ML, Badger GJ, Murray MM. Electron beam sterilization does not have a detrimental effect on the ability of extracellular matrix scaffolds to support in vivo ligament healing. J Orthop Res 2015; 33:1015-23. [PMID: 25676876 PMCID: PMC4517185 DOI: 10.1002/jor.22855] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2014] [Accepted: 01/31/2015] [Indexed: 02/04/2023]
Abstract
Extracellular matrix (ECM) scaffolds have been used to enhance anterior cruciate ligament (ACL) repair in large animal models. To translate this technology to clinical care, identifying a method which effectively sterilizes the material without significantly impairing in vivo function is desirable. Sixteen Yorkshire pigs underwent ACL transection and were randomly assigned to bridge-enhanced ACL repair-primary suture repair of the ACL with addition of autologous blood soaked ECM scaffold--with either (i) an aseptically processed ECM scaffold, or (ii) an electron beam irradiated ECM scaffold. Primary outcome measures included sterility of the scaffold and biomechanical properties of the scaffold itself and the repaired ligament at 8 weeks after surgery. Scaffolds treated with 15 kGy electron beam irradiation had no bacterial or fungal growth noted, while aseptically processed scaffolds had bacterial growth in all tested samples. The mean biomechanical properties of the scaffold and healing ligament were lower in the electron beam group; however, differences were not statistically significant. Electron beam irradiation was able to effectively sterilize the scaffolds. In addition, this technique had only a minimal impact on the in vivo function of the scaffolds when used for ligament healing in the porcine model.
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Affiliation(s)
- Benedikt L. Proffen
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Children's Hospital Boston/Harvard Medical School, Boston, Massachusetts
| | - Gabriel S. Perrone
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Children's Hospital Boston/Harvard Medical School, Boston, Massachusetts
| | - Braden C. Fleming
- Department of Orthopaedics, Bioengineering Labs, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island
| | - Jakob T. Sieker
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Children's Hospital Boston/Harvard Medical School, Boston, Massachusetts
| | | | | | - Gary J. Badger
- Department of Medical Biostatistics, University of Vermont, Burlington, Vermont
| | - Martha M. Murray
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Children's Hospital Boston/Harvard Medical School, Boston, Massachusetts
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Ríos DL, López C, Álvarez ME, Samudio IJ, Carmona JU. Effects over time of two platelet gel supernatants on growth factor, cytokine and hyaluronan concentrations in normal synovial membrane explants challenged with lipopolysaccharide. BMC Musculoskelet Disord 2015; 16:153. [PMID: 26092588 PMCID: PMC4475292 DOI: 10.1186/s12891-015-0605-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Accepted: 05/28/2015] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Platelet-rich plasma (PRP) preparations are a common treatment in osteoarthritis (OA) and inflammatory synovitis. However, there is ambiguity regarding the ideal concentration of leukocytes and platelets in these preparations necessary to induce an adequate anti-inflammatory and anabolic response in joint tissues, such as the synovial membrane. This research aimed to study, in normal synovial membrane explants (SME) challenged with lipopolysaccharide (LPS), the temporal effects (at 48 and 96h) of leukocyte- and platelet-rich gel (L-PRG) and pure platelet-rich gel (P-PRG) supernatants on the production and degradation of platelet associated growth factors (GF) (platelet derived GF isoform BB (PDGF-BB) and transforming growth factor beta-1 (TGF-β1)), pro-inflammatory (tumour necrosis factor alpha (TNF-α)) and anti-inflammatory cytokines (interleukin 4 (IL-4) and IL-1 receptor antagonists (IL-1ra)) and hyaluronan (HA). METHODS Synovial membrane explants (SMEs) from 6 horses were challenged with LPS and cultured for 96h with L-PRG and P-PRG supernatants at concentrations of 25 and 50 %, respectively. The SME culture medium was changed every 48h and used for determination by ELISA of PDGF-BB, TGF-β1, TNF-α, IL-4, IL-1ra and HA. These molecules were also determined in synovial fluid from the horses. RESULTS Both the 25 and 50 % PRG supernatants produced a molecular profile in the culture media unlike that of the SME challenged with LPS only. They presented GF, cytokine and HA concentrations very near to the concentrations of these molecules in normal synovial fluid when compared with the SME control groups (either with LPS or without LPS). However, in comparison with the rest of the SME treated groups, the 25 % L-PRG produced the most IL-1ra, and the 50 % P-PRG induced the sustained production of IL-4 and HA. CONCLUSIONS These in vitro findings suggest that anabolic and anti-inflammatory joint responses depend on the leukocyte and platelet concentration of the PRP preparation and on the volume of this substance injected. Moreover, it is possible, that leukoreduced PRP preparations are more effective for the medical treatment of patients with OA and inflammatory synovitis.
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Affiliation(s)
- Diana L Ríos
- Grupo de Investigación Terapia Regenerativa, Departamento de Salud Animal, Universidad de Caldas, Calle 65 No 26-10, Manizales, Colombia.
| | - Catalina López
- Grupo de Investigación Terapia Regenerativa, Departamento de Salud Animal, Universidad de Caldas, Calle 65 No 26-10, Manizales, Colombia.
| | - María E Álvarez
- Grupo de Investigación Terapia Regenerativa, Departamento de Salud Animal, Universidad de Caldas, Calle 65 No 26-10, Manizales, Colombia.
| | - Ismael J Samudio
- The Terry Fox Laboratory, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, British Columbia, V5Z 1L3, Canada.
| | - Jorge U Carmona
- Grupo de Investigación Terapia Regenerativa, Departamento de Salud Animal, Universidad de Caldas, Calle 65 No 26-10, Manizales, Colombia.
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Proffen BL, Perrone GS, Fleming BC, Sieker JT, Kramer J, Hawes ML, Murray MM. Effect of low-temperature ethylene oxide and electron beam sterilization on the in vitro and in vivo function of reconstituted extracellular matrix-derived scaffolds. J Biomater Appl 2015; 30:435-49. [PMID: 26088294 DOI: 10.1177/0885328215590967] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Reconstituted extracellular matrix (ECM)-derived scaffolds are commonly utilized in preclinical tissue engineering studies as delivery vehicles for cells and growth factors. Translation into clinical use requires identifying a sterilization method that effectively removes bacteria but does not harm scaffold function. To determine effectiveness of sterilization and impact on ECM scaffold integrity and function, low-temperature ethylene oxide and 15 kGy electron beam irradiation techniques were evaluated. Scaffold sterility was assessed in accordance to United States Pharmacopeia Chapter 71. Scaffold matrix degradation was determined in vitro using enzymatic resistance tests and gel electrophoresis. Scaffold mechanics including elastic modulus, yield stress and collapse modulus were tested. Lastly, 14 Yorkshire pigs underwent ACL transection and bio-enhanced ACL repair using sterilized scaffolds. Histologic response of ligament, synovium, and lymph nodes was compared at 4, 6, and 8 weeks. Ethylene oxide as well as electron beam irradiation yielded sterile scaffolds. Scaffold resistance to enzymatic digestion and protein integrity slightly decreased after electron beam irradiation while ethylene oxide altered scaffold matrix. Scaffold elastic modulus and yield stress were increased after electron beam treatment, while collapse modulus was increased after ethylene oxide treatment. No significant changes in ACL dimensions, in vivo scaffold resorption rate, or histologic response of synovium, ligament, and lymph nodes with either terminal sterilization technique were detectable. In conclusion, this study identifies two methods to terminally sterilize an ECM scaffold. In vitro scaffold properties were slightly changed without significantly influencing the biologic responses of the surrounding tissues in vivo. This is a critical step toward translating new tissue engineering strategies to clinical trials.
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Affiliation(s)
- Benedikt L Proffen
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Children's Hospital Boston/Harvard Medical School, Boston, MA, USA
| | - Gabriel S Perrone
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Children's Hospital Boston/Harvard Medical School, Boston, MA, USA
| | - Braden C Fleming
- Department of Orthopaedics, Bioengineering Labs, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, RI, USA
| | - Jakob T Sieker
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Children's Hospital Boston/Harvard Medical School, Boston, MA, USA
| | - Joshua Kramer
- Charter Preclinical Services, 21 Main St., Suite 3A, Hudson, MA, USA
| | - Michael L Hawes
- Charter Preclinical Services, 21 Main St., Suite 3A, Hudson, MA, USA
| | - Martha M Murray
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Children's Hospital Boston/Harvard Medical School, Boston, MA, USA
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PRP Augmentation for ACL Reconstruction. BIOMED RESEARCH INTERNATIONAL 2015; 2015:371746. [PMID: 26064903 PMCID: PMC4430629 DOI: 10.1155/2015/371746] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/29/2014] [Accepted: 08/15/2014] [Indexed: 12/19/2022]
Abstract
Current research is investigating new methods to enhance tissue healing to speed up recovery time and decrease the risk of failure in Anterior Cruciate Ligament (ACL) reconstructive surgery. Biological augmentation is one of the most exploited strategies, in particular the application of Platelet Rich Plasma (PRP). Aim of the present paper is to systematically review all the preclinical and clinical papers dealing with the application of PRP as a biological enhancer during ACL reconstructive surgery. Thirty-two studies were included in the present review. The analysis of the preclinical evidence revealed that PRP was able to improve the healing potential of the tendinous graft both in terms of histological and biomechanical performance. Looking at the available clinical evidence, results were not univocal. PRP administration proved to be a safe procedure and there were some evidences that it could favor the donor site healing in case of ACL reconstruction with patellar tendon graft and positively contribute to graft maturation over time, whereas the majority of the papers did not show beneficial effects in terms of bony tunnels/graft area integration. Furthermore, PRP augmentation did not provide superior functional results at short term evaluation.
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New and emerging strategies in platelet-rich plasma application in musculoskeletal regenerative procedures: general overview on still open questions and outlook. BIOMED RESEARCH INTERNATIONAL 2015; 2015:846045. [PMID: 26075269 PMCID: PMC4436449 DOI: 10.1155/2015/846045] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/17/2014] [Revised: 01/09/2015] [Accepted: 01/13/2015] [Indexed: 02/07/2023]
Abstract
Despite its pervasive use, the clinical efficacy of platelet-rich plasma (PRP) therapy and the different mechanisms of action have yet to be established. This overview of the literature is focused on the role of PRP in bone, tendon, cartilage, and ligament tissue regeneration considering basic science literature deriving from in vitro and in vivo studies. Although this work provides evidence that numerous preclinical studies published within the last 10 years showed promising results concerning the application of PRP, many key questions remain unanswered and controversial results have arisen. Additional preclinical studies are needed to define the dosing, timing, and frequency of PRP injections, different techniques for delivery and location of delivery, optimal physiologic conditions for injections, and the concomitant use of recombinant proteins, cytokines, additional growth factors, biological scaffolds, and stems cells to develop optimal treatment protocols that can effectively treat various musculoskeletal conditions.
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Proffen BL, Sieker JT, Murray M. Bio-enhanced repair of the anterior cruciate ligament. Arthroscopy 2015; 31:990-7. [PMID: 25595694 PMCID: PMC4426066 DOI: 10.1016/j.arthro.2014.11.016] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2014] [Revised: 10/30/2014] [Accepted: 11/13/2014] [Indexed: 02/02/2023]
Abstract
Suture repair of the anterior cruciate ligament (ACL) has been widely abandoned in favor of ACL reconstruction, largely because of the high rates of failure and unreliability of the outcomes after suture repair. However, there have been recent basic science studies that suggest that combining a suture repair with a biological adjunct may improve the results of suture repair of the ACL, with several studies in large animal models showing equivalent strength of an ACL treated with bio-enhanced repaired to that of an ACL graft at 3, 6, and 12 months after surgery. In addition, the groups treated with bio-enhanced repair had significantly less osteoarthritis when compared with the animals undergoing ACL reconstruction. These findings have led to a renewed interest in bio-enhanced primary repair as a way to make repair of the ACL a viable option for a select group of patients in the future.
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Affiliation(s)
- Benedikt L. Proffen
- Sports Medicine Research Laboratory, Department of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School
| | - Jakob T. Sieker
- Sports Medicine Research Laboratory, Department of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School
| | - Martha Murray
- Sports Medicine Research Laboratory, Department of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
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Fleming BC, Proffen BL, Vavken P, Shalvoy MR, Machan JT, Murray MM. Increased platelet concentration does not improve functional graft healing in bio-enhanced ACL reconstruction. Knee Surg Sports Traumatol Arthrosc 2015; 23:1161-70. [PMID: 24633008 PMCID: PMC4167989 DOI: 10.1007/s00167-014-2932-6] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2013] [Accepted: 03/04/2014] [Indexed: 12/19/2022]
Abstract
PURPOSE The use of an extracellular matrix scaffold (ECM) combined with platelets to enhance healing of an anterior cruciate ligament (ACL) graft ("bio-enhanced ACL reconstruction") has shown promise in animal models. However, the effects of platelet concentration on graft healing remain unknown. The objectives of this study were to determine whether increasing the platelet concentration in the ECM scaffold would (1) improve the graft biomechanical properties and (2) decrease cartilage damage after surgery. METHODS Fifty-five adolescent minipigs were randomized to five treatment groups: untreated ACL transection (n = 10), conventional ACL reconstruction (n = 15) and bio-enhanced ACL reconstruction using 1× (n = 10), 3× (n = 10) or 5× (n = 10) platelet-rich plasma. The graft biomechanical properties, anteroposterior (AP) knee laxity, graft histology and macroscopic cartilage integrity were measured at 15 weeks. RESULTS The mean linear stiffness of the bio-enhanced ACL reconstruction procedure using the 1× preparation was significantly greater than traditional reconstruction, while the 3× and 5× preparations were not. The failure loads of all the ACL-reconstructed groups were equivalent but significantly greater than untreated ACL transection. There were no significant differences in the Ligament Maturity Index or AP laxity between reconstructed knees. Macroscopic cartilage damage was relatively minor, though significantly less when the ECM-platelet composite was used. CONCLUSIONS Only the 1× platelet concentration improved healing over traditional ACL reconstruction. Increasing the platelet concentration from 1× to 5× in the ECM scaffold did not further improve the graft mechanical properties. The use of an ECM-platelet composite decreased the amount of cartilage damage seen after ACL surgery.
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Affiliation(s)
- Braden C Fleming
- Department of Orthopaedics, Warren Alpert Medical School of Brown University, Providence, RI, USA,
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Henle P, Röder C, Perler G, Heitkemper S, Eggli S. Dynamic Intraligamentary Stabilization (DIS) for treatment of acute anterior cruciate ligament ruptures: case series experience of the first three years. BMC Musculoskelet Disord 2015; 16:27. [PMID: 25813910 PMCID: PMC4341869 DOI: 10.1186/s12891-015-0484-7] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2014] [Accepted: 01/29/2015] [Indexed: 01/26/2023] Open
Abstract
Background In recent years, the scientific discussion has focused on new strategies to enable a torn anterior cruciate ligament (ACL) to heal into mechanically stable scar tissue. Dynamic intraligamentary stabilization (DIS) was first performed in a pilot study of 10 patients. The purpose of the current study was to evaluate whether DIS would lead to similarly sufficient stability and good clinical function in a larger case series. Methods Acute ACL ruptures were treated by using an internal stabilizer, combined with anatomical repositioning of torn bundles and microfracturing to promote self-healing. Clinical assessment (Tegner, Lysholm, IKDC, and visual analogue scale [VAS] for patient satisfaction scores) and assessment of knee laxity was performed at 3, 6, 12, and 24 months. A one-sample design with a non-inferiority margin was chosen to compare the preoperative and postoperative IKDS and Lysholm scores. Results 278 patients with a 6:4 male to female ratio were included. Average patient age was 31 years. Preoperative mean IKDC, Lysholm, and Tegner scores were 98.8, 99.3, and 5.1 points, respectively. The mean anteroposterior (AP) translation difference from the healthy contralateral knee was 4.7 mm preoperatively. After DIS treatment, the mean 12-month IKDC, Lysholm, and Tegner scores were 93.6, 96.2, and 4.9 points, respectively, and the mean AP translation difference was 2.3 mm. All these outcomes were significantly non-inferior to the preoperative or healthy contralateral values (p < 0.0001). Mean patient satisfaction was 8.8 (VAS 0–10). Eight ACL reruptures occurred and 3 patients reported insufficient subjective stability of the knee at the end of the study period. Conclusions Anatomical repositioning, along with DIS and microfracturing, leads to clinically stable healing of the torn ACL in the large majority of patients. Most patients exhibited almost normal knee function, reported excellent satisfaction, and were able to return to their previous levels of sporting activity. Moreover, this strategy resulted in stable healing of all sutured menisci, which could lower the rate of osteoarthritic changes in future. The present findings support the discussion of a new paradigm in ACL treatment based on preservation and self-healing of the torn ligament.
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Affiliation(s)
- Philipp Henle
- Sonnenhof Orthopaedic Center, Department of Knee Surgery and Sports Traumatology, Buchserstrasse 30, CH-3006, Bern, Switzerland.
| | - Christoph Röder
- Institute for Evaluative Research in Medicine, University of Bern, Stauffacherstrasse 78, CH-3014, Bern, Switzerland.
| | - Gosia Perler
- Institute for Evaluative Research in Medicine, University of Bern, Stauffacherstrasse 78, CH-3014, Bern, Switzerland.
| | - Sven Heitkemper
- Sonnenhof Orthopaedic Center, Department of Knee Surgery and Sports Traumatology, Buchserstrasse 30, CH-3006, Bern, Switzerland.
| | - Stefan Eggli
- Sonnenhof Orthopaedic Center, Department of Knee Surgery and Sports Traumatology, Buchserstrasse 30, CH-3006, Bern, Switzerland.
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Proffen BL, Vavken P, Haslauer CM, Fleming BC, Harris CE, Machan JT, Murray MM. Addition of autologous mesenchymal stem cells to whole blood for bioenhanced ACL repair has no benefit in the porcine model. Am J Sports Med 2015; 43:320-30. [PMID: 25549633 PMCID: PMC4511104 DOI: 10.1177/0363546514559826] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Coculture of mesenchymal stem cells (MSCs) from the retropatellar fat pad and peripheral blood has been shown to stimulate anterior cruciate ligament (ACL) fibroblast proliferation and collagen production in vitro. Current techniques of bioenhanced ACL repair in animal studies involve adding a biologic scaffold, in this case an extracellular matrix-based scaffold saturated with autologous whole blood, to a simple suture repair of the ligament. Whether the enrichment of whole blood with MSCs would further improve the in vivo results of bioenhanced ACL repair was investigated. HYPOTHESIS The addition of MSCs derived from adipose tissue or peripheral blood to the blood-extracellular matrix composite, which is used in bioenhanced ACL repair to stimulate healing, would improve the biomechanical properties of a bioenhanced ACL repair after 15 weeks of healing. STUDY DESIGN Controlled laboratory study. METHODS Twenty-four adolescent Yucatan mini-pigs underwent ACL transection followed by (1) bioenhanced ACL repair, (2) bioenhanced ACL repair with the addition of autologous adipose-derived MSCs, and (3) bioenhanced ACL repair with the addition of autologous peripheral blood derived MSCs. After 15 weeks of healing, the structural properties of the ACL (yield load, failure load, and linear stiffness) were measured. Cell and vascular density were measured in the repaired ACL via histology, and its tissue structure was qualitatively evaluated using the advanced Ligament Maturity Index. RESULTS After 15 weeks of healing, there were no significant improvements in the biomechanical or histological properties with the addition of adipose-derived MSCs. The only significant change with the addition of peripheral blood MSCs was an increase in knee anteroposterior laxity when measured at 30° of flexion. CONCLUSION These findings suggest that the addition of adipose or peripheral blood MSCs to whole blood before saturation of an extracellular matrix carrier with the blood did not improve the functional results of bioenhanced ACL repair after 15 weeks of healing in the pig model. CLINICAL RELEVANCE Whole blood represents a practical biologic additive to ligament repair, and any other additive (including stem cells) should be demonstrated to be superior to this baseline before clinical use is considered.
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Affiliation(s)
- Benedikt L. Proffen
- Department of Orthopaedic Surgery, Boston Children’s Hospital, Boston, Massachusetts, USA
| | - Patrick Vavken
- Department of Orthopaedic Surgery, Boston Children’s Hospital, Boston, Massachusetts, USA
- Department of Orthopaedic Surgery, University Hospital Basel, Switzerland
| | - Carla M. Haslauer
- Department of Orthopaedic Surgery, Boston Children’s Hospital, Boston, Massachusetts, USA
| | - Braden C. Fleming
- Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island, USA
| | - Chad E. Harris
- Department of Hematology/Oncology, Boston Children’s Hospital, Boston, Massachusetts, USA
| | - Jason T. Machan
- Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island, USA
- Biostatistics, Rhode Island Hospital, Providence, Rhode Island, USA
| | - Martha M. Murray
- Department of Orthopaedic Surgery, Boston Children’s Hospital, Boston, Massachusetts, USA
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Nau T, Teuschl A. Regeneration of the anterior cruciate ligament: Current strategies in tissue engineering. World J Orthop 2015; 6:127-136. [PMID: 25621217 PMCID: PMC4303781 DOI: 10.5312/wjo.v6.i1.127] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2014] [Revised: 06/19/2014] [Accepted: 07/29/2014] [Indexed: 02/06/2023] Open
Abstract
Recent advancements in the field of musculoskeletal tissue engineering have raised an increasing interest in the regeneration of the anterior cruciate ligament (ACL). It is the aim of this article to review the current research efforts and highlight promising tissue engineering strategies. The four main components of tissue engineering also apply in several ACL regeneration research efforts. Scaffolds from biological materials, biodegradable polymers and composite materials are used. The main cell sources are mesenchymal stem cells and ACL fibroblasts. In addition, growth factors and mechanical stimuli are applied. So far, the regenerated ACL constructs have been tested in a few animal studies and the results are encouraging. The different strategies, from in vitro ACL regeneration in bioreactor systems to bio-enhanced repair and regeneration, are under constant development. We expect considerable progress in the near future that will result in a realistic option for ACL surgery soon.
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Dynamic intraligamentary stabilization: novel technique for preserving the ruptured ACL. Knee Surg Sports Traumatol Arthrosc 2015; 23:1215-21. [PMID: 24651979 PMCID: PMC4371814 DOI: 10.1007/s00167-014-2949-x] [Citation(s) in RCA: 82] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2012] [Accepted: 03/11/2014] [Indexed: 02/07/2023]
Abstract
PURPOSE Replacement of the torn anterior cruciate ligament (ACL) with a transplant is today`s gold standard. A new technique for preserving and healing the torn ACL is presented. HYPOTHESIS a dynamic intraligamentary stabilization (DIS) that provides continuous postinjury stability of the knee and ACL in combination with biological improvement of the healing environment [leucocyte- and platelet-rich fibrin (L-PRF) and microfracturing] should enable biomechanically stable ACL self-healing. METHODS Ten sportive patients were treated by DIS employing an internal stabilizer to keep the unstable knee in a posterior translation, combined with microfracturing and platelet-rich fibrin induction at the rupture site to promote self-healing. Postoperative clinical [Tegner, Lysholm, International Knee Documentation Committee (IKDC), visual analogue scale patient satisfaction score] and radiological evaluation, as well as assessment of knee laxity was performed at 6 weeks, 3, 6, 12, and 24 months. RESULTS One patient had a re-rupture 5 months postoperative and was hence excluded from further follow-ups. The other nine patients presented the following outcomes at 24 months: median Lysholm score of 100; IKDC score of 98 (97-100); median Tegner score of 6 (range 9-5); anterior translation difference of 1.4 mm (-1 to 3 mm); median satisfaction score of 9.8 (9-10). MRI showed scarring and continuity of the ligament in all patients. CONCLUSIONS DIS combined with microfracturing and L-PRF resulted in stable clinical and radiological healing of the torn ACL in all but one patient of this first series. They attained normal knee scores, reported excellent satisfaction and could return to their previous levels of sporting activity. LEVEL OF EVIDENCE Case series with no comparison group, Level IV.
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O'Shea CM, Werre SR, Dahlgren LA. Comparison of platelet counting technologies in equine platelet concentrates. Vet Surg 2014; 44:304-13. [PMID: 25307726 DOI: 10.1111/j.1532-950x.2014.12290.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Accepted: 02/01/2014] [Indexed: 11/30/2022]
Abstract
OBJECTIVE (1) To compare the performance of 4 platelet counting technologies in equine platelet concentrates and (2) to evaluate the ability of the Magellan platelet rich plasma (PRP) system to concentrate equine platelets. STUDY DESIGN Experimental study to assess method agreement. ANIMALS Adult mixed breed horses (n = 32). METHODS Acid citrate dextrose-A anti-coagulated whole blood was collected and PRP produced using the Magellan system according to the manufacturer's instructions. Platelets were quantified using 4 counting methods: optical scatter (Advia 2120), impedance (CellDyn 3700), hand counting, and fluorescent antibody flow cytometry. Platelet concentrations were compared using Passing and Bablok regression analyses and mixed model ANOVA. Significance was set at P < .05. RESULTS Platelet concentrations measured in identical PRP samples were consistently higher for the Advia 2120 than the CellDyn 3700. Systematic and proportional biases were observed between these 2 automated methods when analyzed by regression analysis of the larger sample size. No bias (systematic or proportional) was observed among any of the other counting methods. Despite the bias detected between the 2 automated systems, there were no significant differences on average among the 4 counting methods evaluated, based on the ANOVA. The Magellan system consistently generated high platelet concentrations as well as higher than expected WBC concentrations. CONCLUSIONS The Magellan system delivered desirably high platelet concentrations; however, WBC concentrations may be unacceptably high for some orthopedic applications. All 4 platelet counting methods tested were equivalent on average and therefore suitable for quantifying platelets in equine PRP used for clinical applications.
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Affiliation(s)
- Caitlin M O'Shea
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia
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Kaniki N, Willits K, Mohtadi NGH, Fung V, Bryant D. A retrospective comparative study with historical control to determine the effectiveness of platelet-rich plasma as part of nonoperative treatment of acute achilles tendon rupture. Arthroscopy 2014; 30:1139-45. [PMID: 24997748 DOI: 10.1016/j.arthro.2014.04.086] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2013] [Revised: 03/28/2014] [Accepted: 04/10/2014] [Indexed: 02/02/2023]
Abstract
PURPOSE The aim of this study was to evaluate the effectiveness of platelet-rich plasma (PRP) in the nonoperative treatment of acute Achilles tendon rupture. METHODS This was a comparative study that included a prospective cohort and a historical control group. The control group was formed from a randomized trial in which one arm of the trial underwent nonoperative treatment, including accelerated functional rehabilitation after acute Achilles tendon rupture identical to that performed in the prospective treatment group. Patients in the prospective group were recruited consecutively and were administered 2 injections of PRP during the first 2 weeks after the injury. The primary outcome was isokinetic plantar flexion strength at 1 and 2 years after injury. Secondary outcomes included range of motion (ROM), calf circumference, and Leppilahti score. The ankle-hindfoot scale (American Orthopedic Functional Ankle Scale [AOFAS]) was administered to patients who received the PRP injection in the prospective group but was not measured for the historical group. RESULTS A total of 73 patients participated in the prospective PRP study group and were compared with a retrospective control group of 72 patients from a previous randomized controlled trial (RCT). The mean difference between groups in isokinetic plantar flexion strength (injured/uninjured) at 1 year after injury was -4.3% (95% confidence interval [CI], -15.9 to 7.3; P = .5) and 2.4% (95% CI, -8.6 to 13.5; P = .7) at 30°/s and 60°/s, respectively. Results at 2 years after injury were -3.1% (95% CI, -13.5 to 7.2; P = .6) and 4.8% (95% CI, -3.5 to 13.1; P = .3) at 30°/s and 60°/s, respectively. All secondary outcomes were also not statistically different. CONCLUSIONS The results of this study suggest that there is no measurable clinical benefit to the addition of PRP to the treatment regimen for nonoperatively treated acute Achilles tendon rupture. LEVEL OF EVIDENCE Level III, retrospective comparative study.
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Affiliation(s)
- Nicole Kaniki
- Faculty of Health Sciences, Health and Rehabilitation Sciences, Western University, London, Ontario, Canada
| | - Kevin Willits
- Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; Faculty of Health Sciences, School of Kinesiology, Western University, London, Ontario, Canada; Fowler Kennedy Sports Medicine Clinic, London, Ontario, Canada.
| | | | - Vincent Fung
- Fowler Kennedy Sports Medicine Clinic, London, Ontario, Canada
| | - Dianne Bryant
- Faculty of Health Sciences, Health and Rehabilitation Sciences, Western University, London, Ontario, Canada; Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; Faculty of Health Sciences, School of Kinesiology, Western University, London, Ontario, Canada; Faculty of Health Sciences, School of Physical Therapy, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Faculty of Medicine, McMaster University, Hamilton, Ontario, Canada
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Prosecká E, Rampichová M, Litvinec A, Tonar Z, Králíčková M, Vojtová L, Kochová P, Plencner M, Buzgo M, Míčková A, Jančář J, Amler E. Collagen/hydroxyapatite scaffold enriched with polycaprolactone nanofibers, thrombocyte-rich solution and mesenchymal stem cells promotes regeneration in large bone defect in vivo. J Biomed Mater Res A 2014; 103:671-82. [PMID: 24838634 DOI: 10.1002/jbm.a.35216] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2013] [Revised: 04/09/2014] [Accepted: 05/01/2014] [Indexed: 12/30/2022]
Abstract
A three-dimensional scaffold of type I collagen and hydroxyapatite enriched with polycaprolactone nanofibers (Coll/HA/PCL), autologous mesenchymal stem cells (MSCs) in osteogenic media, and thrombocyte-rich solution (TRS) was an optimal implant for bone regeneration in vivo in white rabbits. Nanofibers optimized the viscoelastic properties of the Coll/HA scaffold for bone regeneration. MSCs and TRS in the composite scaffold improved bone regeneration. Three types of Coll/HA/PCL scaffold were prepared: an MSC-enriched scaffold, a TRS-enriched scaffold, and a scaffold enriched with both MSCs and TRS. These scaffolds were implanted into femoral condyle defects 6 mm in diameter and 10-mm deep. Untreated defects were used as a control. Macroscopic and histological analyses of the regenerated tissue from all groups were performed 12 weeks after implantation. The highest volume and most uniform distribution of newly formed bone occurred in defects treated with scaffolds enriched with both MSCs and TRS compared with that in defects treated with scaffolds enriched by either component alone. The modulus of elasticity in compressive testing was significantly higher in the Coll/HA/PCL scaffold than those without nanofibers. The composite Coll scaffold functionalized with PCL nanofibers and enriched with MSCs and TRS appears to be a novel treatment for bone defects.
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Affiliation(s)
- E Prosecká
- Institute of Biophysics, 2nd Faculty of Medicine, Charles University in Prague, V Uvalu 84, 150 06, Prague, Czech Republic; Department of Tissue Engineering, Institute of Experimental Medicine ASCR v.v.i., Vídeňská 1083, 14240, Prague, Czech Republic; Student Science s.r.o., Horní Podluží 237, Horní Podluží, 407 57, Czech Republic
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Yoshida R, Cheng M, Murray MM. Increasing platelet concentration in platelet-rich plasma inhibits anterior cruciate ligament cell function in three-dimensional culture. J Orthop Res 2014; 32:291-5. [PMID: 24122902 PMCID: PMC3945668 DOI: 10.1002/jor.22493] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2012] [Accepted: 08/29/2013] [Indexed: 02/04/2023]
Abstract
Tissue engineering is one new strategy being developed to treat ACL ruptures. One such approach is bio-enhanced ACL repair, where a suture repair is supplemented with a bio-active scaffold containing platelets. However, the optimal concentration of platelets to stimulate ACL healing is not known. We hypothesized that increasing platelet concentrations in the scaffold would enhance critical cell behaviors. Porcine ACL fibroblasts were obtained from explant culture and suspended in platelet poor plasma (PPP), 1× platelet-rich plasma (PRP), 3× PRP, 5× PRP, or phosphate buffered saline (PBS). The cell suspensions were cultured in a 3D collagen scaffold. Cellular metabolism (MTT assay), apoptosis (TUNEL assay), and gene expression for type I and type III collagen were measured. 1× PRP significantly outperformed 5× PRP in all parameters studied: Type I and III collagen gene expression, apoptosis prevention, and cell metabolism stimulation. ACL fibroblasts cultured with 1× PRP had the highest type I and type III collagen gene expression. 1× PRP and PPP groups had the highest cell metabolism and lowest apoptosis rates. Concentration of platelets had significant effects on the behavior of ACL fibroblasts; thus, it is an important parameter that should be specified in clinical or basic science studies.
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Affiliation(s)
- Ryu Yoshida
- Department of Orthopaedic Surgery; Children's Hospital Boston; Hunnewell 2, 300 Longwood Ave Boston Massachusetts 02115
| | - Mingyu Cheng
- Department of Orthopaedic Surgery; Children's Hospital Boston; Hunnewell 2, 300 Longwood Ave Boston Massachusetts 02115
| | - Martha M. Murray
- Department of Orthopaedic Surgery; Children's Hospital Boston; Hunnewell 2, 300 Longwood Ave Boston Massachusetts 02115
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Boswell SG, Schnabel LV, Mohammed HO, Sundman EA, Minas T, Fortier LA. Increasing platelet concentrations in leukocyte-reduced platelet-rich plasma decrease collagen gene synthesis in tendons. Am J Sports Med 2014; 42:42-9. [PMID: 24136860 DOI: 10.1177/0363546513507566] [Citation(s) in RCA: 133] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Platelet-rich plasma (PRP) is used for the treatment of tendinopathy. There are numerous PRP preparations, and the optimal combination of platelets and leukocytes is not known. HYPOTHESIS Within leukocyte-reduced PRP (lrPRP), there is a plateau effect of platelet concentration, with increasing platelet concentrations being detrimental to extracellular matrix synthesis. STUDY DESIGN Controlled laboratory study. METHODS Different formulations of lrPRP with respect to the platelet:leukocyte ratio were generated from venous blood of 8 horses. Explants of the superficial digital flexor tendon were cultured in lrPRP products for 96 hours. Platelet-derived growth factor-BB (PDGF-BB), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), and interleukin-1β (IL-1β) concentrations were determined in the media by enzyme-linked immunosorbent assay. Gene expression in tendon tissue for collagen type I and III (COL1A1 and COL3A1, respectively), matrix metalloproteinase-3 and -13 (MMP-3 and MMP-13, respectively), cartilage oligomeric matrix protein (COMP), and IL-1β was determined. Data were divided into 3 groups of lrPRP based on the ratio of platelets:leukocytes and evaluated to determine the effect of platelet concentration. RESULTS Complete blood counts verified leukocyte reduction and platelet enrichment in all PRP preparations. In the lrPRP preparation, the anabolic growth factors PDGF-BB and TGF-β1 were increased with increasing platelet concentrations, and the catabolic cytokine IL-1β was decreased with increasing platelet concentrations. Increasing the platelet concentration resulted in a significant reduction in COL1A1 and COL3A1 synthesis in tendons. CONCLUSION Increasing the platelet concentration within lrPRP preparations results in the delivery of more anabolic growth factors and less proinflammatory cytokines, but the biological effect on tendons is diminished metabolism as indicated by a decrease in the synthesis of both COL1A1 and COL3A1. Together, this information suggests that minimizing leukocytes in PRP is more important than maximizing platelet numbers with respect to decreasing inflammation and enhancing matrix gene synthesis. CLINICAL RELEVANCE This study suggests that reducing leukocytes to minimize catabolic signaling appears to be more important than increasing platelets in an effort to maximize anabolic signaling. Further, a maximum biological threshold of benefit was demonstrated with regard to the number of platelets beyond which further increases in platelet concentration did not result in further anabolic upregulation. In vivo investigations documenting the use of platelets for the treatment of tendinopathy are justified as well as further in vitro characterization of the ideal PRP product for the treatment of tendinopathy and other musculoskeletal applications.
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Affiliation(s)
- Stacie G Boswell
- Lisa A. Fortier, Cornell University, VMC C3-181, Ithaca, NY 14853.
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Combined treatment with platelet-rich plasma and brain-derived neurotrophic factor-overexpressing bone marrow stromal cells supports axonal remyelination in a rat spinal cord hemi-section model. Cytotherapy 2013; 15:792-804. [PMID: 23731762 DOI: 10.1016/j.jcyt.2013.04.004] [Citation(s) in RCA: 116] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2012] [Revised: 03/24/2013] [Accepted: 04/07/2013] [Indexed: 11/21/2022]
Abstract
BACKGROUND AIMS Combining biologic matrices is becoming a better choice to advance stem cell-based therapies. Platelet-rich plasma (PRP) is a biologic product of concentrated platelets and has been used to promote regeneration of peripheral nerves after injury. We examined whether PRP could induce rat bone marrow stromal cells (BMSCs) differentiation in vitro and whether a combination of BMSCs, PRP and brain-derived neurotrophic factor (BDNF) could provide additive therapeutic benefits in vivo after spinal cord injury (SCI). METHODS BMSCs and BDNF-secreting BMSCs (BDNF-BMSCs) were cultured with PRP for 7 days and 21 days, respectively, and neurofilament (NF)-200, glial fibrillary acidic protein (GFAP), microtubule-associated protein 2 (MAP2) and ribosomal protein S6 kinase (p70S6K) gene levels were assessed. After T10 hemi-section in 102 rats, 15-μL scaffolds (PRP alone, BMSCs, PRP/BMSCs, BDNF-BMSCs or PRP/BDNF-BMSCs) were transplanted into the lesion area, and real-time polymerase chain reaction, Western blot, immunohistochemistry and ultrastructural studies were performed. RESULTS The messenger RNA expression of NF-200, GFAP, MAP2 and p70S6K was promoted in BMSCs and BDNF-BMSCs after culture with PRP in vitro. BDNF levels were significantly higher in the injured spinal cord after implantation of BDNF-BMSCs. In the PRP/BDNF-BMSCs group at 8 weeks postoperatively, more GFAP was observed, with less accumulation of astrocytes at the graft-host interface. Rats that received PRP and BDNF-BMSC implants showed enhanced hind limb locomotor performance at 8 weeks postoperatively compared with control animals, with more axonal remyelination. CONCLUSIONS A combined treatment comprising PRP and BDNF-overexpressing BMSCs produced beneficial effects in rats with regard to functional recovery after SCI through enhancing migration of astrocytes into the transplants and axonal remyelination.
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Abstract
IMPORTANCE The promising therapeutic potential and regenerative properties of platelet-rich plasma (PRP) have rapidly led to its widespread clinical use in musculoskeletal injury and disease. Although the basic scientific rationale surrounding PRP products is compelling, the clinical application has outpaced the research. OBJECTIVE The purpose of this article is to examine the current concepts around the basic science of PRP application, different preparation systems, and clinical application of PRP in disorders in the knee. EVIDENCE ACQUISITION A systematic search of PubMed for studies that evaluated the basic science, preparation and clinical application of platelet concentrates was performed. The search used terms, including platelet-rich plasma or PRP preparation, activation, use in the knee, cartilage, ligament, and meniscus. Studies found in the initial search and related studies were reviewed. RESULTS A comprehensive review of the literature supports the potential use of PRP both nonoperatively and intraoperatively, but highlights the absence of large clinical studies and the lack of standardization between method, product, and clinical efficacy. Conclusions and Relevance. In addition to the call for more randomized, controlled clinical studies to assess the clinical effect of PRP, at this point, it is necessary to investigate PRP product composition and eventually have the ability to tailor the therapeutic product for specific indications.
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Affiliation(s)
- Kathryn B. Metcalf
- Santa Monica Orthopaedic and Sports Medicine Group, Santa Monica, CA, USA
| | - Bert R. Mandelbaum
- Santa Monica Orthopaedic and Sports Medicine Group, Santa Monica, CA, USA
| | - C. Wayne McIlwraith
- Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA
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Murray MM, Fleming BC. Biology of anterior cruciate ligament injury and repair: Kappa delta ann doner vaughn award paper 2013. J Orthop Res 2013; 31:1501-6. [PMID: 23818453 PMCID: PMC3750083 DOI: 10.1002/jor.22420] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2013] [Accepted: 06/06/2013] [Indexed: 02/04/2023]
Abstract
Anterior cruciate ligament (ACL) injuries are currently treated by removing the injured ligament and replacing it with a tendon graft. Recent studies have examined alternative treatment methods, including repair and regeneration of the injured ligament. In order to make such an approach feasible, a basic understanding of ACL biology and its response to injury is needed. Identification of obstacles to native ACL healing can then be identified and potentially resolved using tissue engineering strategies-first, with in vitro screening assays, and then with in vivo models of efficacy and safety. This Perspectives paper outlines this path of discovery for optimizing ACL healing using a bio-enhanced repair technique. This journey required constructing indices of the functional tissue response, pioneering physiologically based methods of biomechanical testing, developing, and validating clinically relevant animal models, and creating and optimizing translationally feasible scaffolds, surgical techniques, and biologic additives. Using this systematic translational approach, "bio-enhanced" ACL repair has been advanced to the point where it may become an option for future treatment of acute ACL injuries and the prevention of subsequent post-traumatic osteoarthritis associated with this injury.
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Affiliation(s)
- Martha Meaney Murray
- Department of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School, Division of Sports Medicine, Boston, MA
| | - Braden C. Fleming
- Department of Orthopaedics, Bioengineering Labs, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, RI,Center for Biomedical Engineering, Brown University, Providence, RI
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