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Qi L, Hong S, Zhao T, Yan J, Ge W, Wang J, Fang X, Jiang W, Shen SG, Zhang L. DNA Tetrahedron Delivering miR-21-5p Promotes Senescent Bone Defects Repair through Synergistic Regulation of Osteogenesis and Angiogenesis. Adv Healthc Mater 2024; 13:e2401275. [PMID: 38979868 DOI: 10.1002/adhm.202401275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Revised: 06/08/2024] [Indexed: 07/10/2024]
Abstract
Compromised osteogenesis and angiogenesis is the character of stem cell senescence, which brought difficulties for bone defects repairing in senescent microenvironment. As the most abundant bone-related miRNA, miRNA-21-5p plays a crucial role in inducing osteogenic and angiogenic differentiation. However, highly efficient miR-21-5p delivery still confronts challenges including poor cellular uptake and easy degradation. Herein, TDN-miR-21-5p nanocomplex is constructed based on DNA tetrahedral (TDN) and has great potential in promoting osteogenesis and alleviating senescence of senescent bone marrow stem cells (O-BMSCs), simultaneously enhancing angiogenic capacity of senescent endothelial progenitor cells (O-EPCs). Of note, the activation of AKT and Erk signaling pathway may direct regulatory mechanism of TDN-miR-21-5p mediated osteogenesis and senescence of O-BMSCs. Also, TDN-miR-21-5p can indirectly mediate osteogenesis and senescence of O-BMSCs through pro-angiogenic growth factors secreted from O-EPCs. In addition, gelatin methacryloyl (GelMA) hydrogels are mixed with TDN and TDN-miR-21-5p to fabricate delivery scaffolds. TDN-miR-21-5p@GelMA scaffold exhibits greater bone repair with increased expression of osteogenic- and angiogenic-related markers in senescent critical-size cranial defects in vivo. Collectively, TDN-miR-21-5p can alleviate senescence and induce osteogenesis and angiogenesis in senescent microenvironment, which provides a novel candidate strategy for senescent bone repair and widen clinical application of TDNs-based gene therapy.
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Affiliation(s)
- Lei Qi
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, P. R. China
| | - Shebin Hong
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, P. R. China
| | - Tong Zhao
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, P. R. China
| | - Jinge Yan
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, P. R. China
| | - Weiwen Ge
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, P. R. China
| | - Jing Wang
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, P. R. China
| | - Xin Fang
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, P. R. China
| | - Weidong Jiang
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, P. R. China
| | - Steve Gf Shen
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, P. R. China
| | - Lei Zhang
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, P. R. China
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Regmi A, Niraula BB, Maheshwari V, Nongdamba H, Karn R, Bondarde P, Anand U, Dhingra M, Kandwal P. Establishing a bone bank within a hospital setting in India: early insights from a tertiary care center in Northern India-a review article. Cell Tissue Bank 2024; 25:873-882. [PMID: 39014032 DOI: 10.1007/s10561-024-10146-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 06/17/2024] [Indexed: 07/18/2024]
Abstract
When addressing bone defects resulting from trauma, infection, or tumors, the use of allogenic bone is often necessary. While autografts are considered the standard, they have limitations and can lead to donor site morbidity. Consequently, there has been exploration into the feasibility of utilizing allogenic bone and bone graft replacements. Allogenic bone transplants are acquired from donors following rigorous procurement, sterile processing, and donor screening procedures. To ensure the safe storage and effective utilization of allograft material, a bone banking system is employed. Establishing and managing an orthopedic bone bank, entails navigating complex legal and medical organizational aspects. This paper examines the establishment and operation of bone banks in India, drawing upon our first-hand experience in managing one at a tertiary care center in Northern India.Level of evidence: Level IV.
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Affiliation(s)
- Anil Regmi
- All India Institute of Medical Sciences, Rishikesh, India
| | | | | | | | - Rahul Karn
- All India Institute of Medical Sciences, Rishikesh, India
| | | | - Utsav Anand
- All India Institute of Medical Sciences, Rishikesh, India
| | - Mohit Dhingra
- All India Institute of Medical Sciences, Rishikesh, India.
| | - Pankaj Kandwal
- All India Institute of Medical Sciences, Rishikesh, India
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Wang R, He X, Chen Z, Su S, Bai J, Liu H, Zhou F. A nanoparticle reinforced microporous methacrylated silk fibroin hydrogel to promote bone regeneration. Biomater Sci 2024; 12:2121-2135. [PMID: 38456326 DOI: 10.1039/d3bm01901b] [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: 03/09/2024]
Abstract
Natural polymer-based hydrogels have been widely applied in bone tissue engineering due to their excellent biocompatibility and outstanding ability of drug encapsulation. However, they have relatively weak mechanical properties and lack bioactivity. Hence, we developed a bioactive nanoparticle composite hydrogel by incorporating LAPONITE®, which is an osteo-inductive inorganic nanoparticle. The incorporation of the nanoparticle significantly enhanced its mechanical properties. In vitro evaluation indicated that the nanocomposite hydrogel could exhibit good biocompatibility. Besides, the nanocomposite hydrogel was proved to have excellent osteogenic ability with up-regulated expression of osteogenic markers such as type I collagen (COL-I), runt-related transcription factor-2 (Runx-2) and osteocalcin (OCN). Furthermore, the in vivo study confirmed that the composite nanocomposite hydrogel could significantly promote new bone formation, providing a prospective strategy for bone tissue regeneration.
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Affiliation(s)
- Ruideng Wang
- Department of Orthopedics, Peking University Third Hospital, Beijing, China.
- Engineering Research Center of Bone and Joint Precision Medicine, Beijing, China
| | - Xi He
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
| | - Zhengyang Chen
- Department of Orthopedics, Peking University Third Hospital, Beijing, China.
- Engineering Research Center of Bone and Joint Precision Medicine, Beijing, China
| | - Shilong Su
- Department of Orthopedics, Peking University Third Hospital, Beijing, China.
- Engineering Research Center of Bone and Joint Precision Medicine, Beijing, China
| | - Jinwu Bai
- Department of Orthopedics, Peking University Third Hospital, Beijing, China.
- Engineering Research Center of Bone and Joint Precision Medicine, Beijing, China
| | - Haifeng Liu
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
| | - Fang Zhou
- Department of Orthopedics, Peking University Third Hospital, Beijing, China.
- Engineering Research Center of Bone and Joint Precision Medicine, Beijing, China
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Sui X, Zhang H, Yao J, Yang L, Zhang X, Li L, Wang J, Li M, Liu Z. 3D printing of 'green' thermo-sensitive chitosan-hydroxyapatite bone scaffold based on lyophilized platelet-rich fibrin. Biomed Mater 2023; 18. [PMID: 36758238 DOI: 10.1088/1748-605x/acbad5] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 02/09/2023] [Indexed: 02/11/2023]
Abstract
The critical bone defect is still an urgent problem in the field of bone repair. Here, we reported a new type of chitosan (CS)-hydroxyapatite (HAP) scaffolds based on lyophilized platelet-rich fibrin (L-PRF) for releasing abundant growth factors to realize their respective functions. It also has strong mechanical properties to maintain the stability of the bone repair environment. However, acid-soluble CS hydrogels often contain toxic and organic solvents. Moreover, chemical agents may be used for cross-linking for better mechanical properties, further increasing cytotoxicity. In this study, we used an alkali/urea dissolution system to dissolve CS, which improved its mechanical properties and made it thermo-sensitive. Finally, the L-PRF-CS-HAP (P-C-H) composite scaffold was constructed by extrusion-based printing. The results showed that the printing ink had desirable printability and temperature sensitivity. The compressive properties of the scaffolds exhibited a trend of decline with L-PRF content increasing, but all of them could meet the strength of cancellous bone. Meanwhile, the scaffolds had high hydrophilicity, porosity, and could be degraded stablyin vitro. The antibacterial properties of the scaffolds were also verified, greatly reducing the risk of infection during bone repair. It was also demonstrated that the release time of growth factor from L-PRF was significantly prolonged, and growth factor could still be detected after 35 d of sustained release. The capacity of cells to proliferate increased as the number of L-PRF components increased, indicating that L-PRF still exhibited biological activity after 3D printing.
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Affiliation(s)
- Xin Sui
- Hospital of Stomatology, Jilin University, 130021, People's Republic of China.,Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Changchun 130021, People's Republic of China
| | - Huili Zhang
- Hospital of Stomatology, Jilin University, 130021, People's Republic of China.,Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Changchun 130021, People's Republic of China
| | - Jingjing Yao
- Hospital of Stomatology, Jilin University, 130021, People's Republic of China.,Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Changchun 130021, People's Republic of China
| | - Liuqing Yang
- Hospital of Stomatology, Jilin University, 130021, People's Republic of China.,Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Changchun 130021, People's Republic of China
| | - Xiao Zhang
- Hospital of Stomatology, Jilin University, 130021, People's Republic of China.,Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Changchun 130021, People's Republic of China
| | - Lingfeng Li
- Hospital of Stomatology, Jilin University, 130021, People's Republic of China.,Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Changchun 130021, People's Republic of China
| | - Jue Wang
- Hospital of Stomatology, Jilin University, 130021, People's Republic of China.,Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Changchun 130021, People's Republic of China
| | - Meihui Li
- Hospital of Stomatology, Jilin University, 130021, People's Republic of China.,Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Changchun 130021, People's Republic of China
| | - Zhihui Liu
- Hospital of Stomatology, Jilin University, 130021, People's Republic of China.,Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Changchun 130021, People's Republic of China
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Wu S, Quan K, Mei J, Dai M, Song S. Cortical allograft strut augmented with platelet-rich plasma for the treatment of long bone non-union in lower limb- a pilot study. BMC Musculoskelet Disord 2022; 23:512. [PMID: 35637466 PMCID: PMC9150336 DOI: 10.1186/s12891-022-05375-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 04/25/2022] [Indexed: 11/18/2022] Open
Abstract
Background The autogenous iliac bone graft is the first choice of surgical treatment for long bone non-union. However, many factors limit the use of autogenous bone, such as insufficient bone harvest and complications in the donor site. This study aimed to pilot-test the effectiveness of the cortical allograft strut augmented with Platelet-rich plasma (PRP) on long bone non-union in the lower limb. Method This study was a one-armed pilot trial, with thirteen men and four women patients scheduled for surgery. Revision surgery for managing long bone non-union included debridement, internal fixation of the cortical allograft strut, and adding PRP in the fracture site. After surgery, outcome measurements of healing rate, healing time, the incidence of revision, and complications, were assessed at least one-year follow-up. Results Fourteen of seventeen participants completed all follow-ups. The mean age of 14 patients was 35.9 years (range, 18–56 years), and the mean BMI was 22.44 ± 1.53 kg/m2. All nonunions united after the operation. The mean healing time was 4.6 ± 0.7 months. There was no revision or complication. Conclusion Cortical allograft strut augmented with PRP led to healing long bone non-union in the lower limb. More clinical research is required before widespread use.
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Affiliation(s)
- Shenghui Wu
- Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 YiShan Road, Shanghai, 200233, China
| | - Kun Quan
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Jiong Mei
- Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 YiShan Road, Shanghai, 200233, China
| | - Min Dai
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Sa Song
- Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 YiShan Road, Shanghai, 200233, China.
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Ren S, Tang X, Liu L, Meng F, Yang X, Li N, Zhang Z, Aimaijiang M, Liu M, Liu X, Wang H, Huangfu H, Wang H, Zhang J, Li D, Zhou Y. Reinforced Blood-Derived Protein Hydrogels Enable Dual-Level Regulation of Bio-Physiochemical Microenvironments for Personalized Bone Regeneration with Remarkable Enhanced Efficacy. NANO LETTERS 2022; 22:3904-3913. [PMID: 35522592 DOI: 10.1021/acs.nanolett.2c00057] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Physiological microenvironment engineering has shown great promise in combating a variety of diseases. Herein, we present the rational design of reinforced and injectable blood-derived protein hydrogels (PDA@SiO2-PRF) composed of platelet-rich fibrin (PRF), polydopamine (PDA), and SiO2 nanofibers that can act as dual-level regulators to engineer the microenvironment for personalized bone regeneration with high efficacy. From the biophysical level, PDA@SiO2-PRF with high stiffness can withstand the external loading and maintaining the space for bone regeneration in bone defects. Particularly, the reinforced structure of PDA@SiO2-PRF provides bone extracellular matrix (ECM)-like functions to stimulate osteoblast differentiation via Yes-associated protein (YAP) signaling pathway. From the biochemical level, the PDA component in PDA@SiO2-PRF hinders the fast degradation of PRF to release autologous growth factors in a sustained manner, providing sustained osteogenesis capacity. Overall, the present study offers a dual-level strategy for personalized bone regeneration by engineering the biophysiochemical microenvironment to realize enhanced osteogenesis efficacy.
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Affiliation(s)
- Sicong Ren
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, 763 Heguang Road, Changchun 130021, P.R. China
| | - Xiaoduo Tang
- Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P.R. China
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, 2699 Qianjin Avenue, Changchun 130012, P.R. China
| | - Lijun Liu
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, 763 Heguang Road, Changchun 130021, P.R. China
| | - Fanrong Meng
- Department of Stomatology, The Aviation General Hospital, 3 Beiyuan Road, Beijing 100000, P.R. China
| | - Xudong Yang
- School of Chemical Engineering, Advanced Institute of Materials Science, Changchun University of Technology, 2055 Yan'an street, Changchun 130012, P.R. China
| | - Nuo Li
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, 763 Heguang Road, Changchun 130021, P.R. China
| | - Zhiying Zhang
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, 763 Heguang Road, Changchun 130021, P.R. China
| | - Maierhaba Aimaijiang
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, 763 Heguang Road, Changchun 130021, P.R. China
| | - Manxuan Liu
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, 763 Heguang Road, Changchun 130021, P.R. China
| | - Xinchen Liu
- Department of Endodontics, Hospital of Stomatology, Jilin University, 763 Heguang Road, Changchun 130021, P.R. China
| | - Hanchi Wang
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, 763 Heguang Road, Changchun 130021, P.R. China
| | - Huimin Huangfu
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, 763 Heguang Road, Changchun 130021, P.R. China
| | - Huan Wang
- State Key Laboratory of Rare Earth Resources Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, P.R. China
| | - Junhu Zhang
- Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, P.R. China
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, 2699 Qianjin Avenue, Changchun 130012, P.R. China
| | - Daowei Li
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, 763 Heguang Road, Changchun 130021, P.R. China
| | - Yanmin Zhou
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, 763 Heguang Road, Changchun 130021, P.R. China
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Hamati FJ, Siotos C, Terhune EB, Williams JC, Dorafshar AH. Free Fibular Flap and Fibular Graft Double-Strut Tunneling to Fill a Large Tibial Plateau Defect. EPLASTY 2021; 21:e9. [PMID: 35652082 PMCID: PMC9129069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Introduction Bony defects resulting from trauma, osteomyelitis, and tumor resection pose significant reconstructive challenges. Free fibular flaps (FFFs) are an excellent option, especially for large defects in the tibia. Case presentation In this article, the authors review a case of a 60-year-old male who underwent FFF and fibular graft double-strut tunneling to fill a large tibial plateau defect. Conclusion The use of the FFF provides an excellent option for reconstructing long bone large defects (defects > 6 cm). The case presented in this report indicates an expanded application of this technique in treating defects secondary to chronic osteomyelitis in infected tibial plateau nonunion.
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Affiliation(s)
- Fadi J. Hamati
- Division of Plastic and Reconstructive Surgery, Rush University Medical Center, Chicago, IL
| | - Charalampos Siotos
- Division of Plastic and Reconstructive Surgery, Rush University Medical Center, Chicago, IL
| | - E. Bailey Terhune
- Midwest Orthopaedics at Rush, Rush University Medical Center, Chicago, IL
| | - Joel C. Williams
- Midwest Orthopaedics at Rush, Rush University Medical Center, Chicago, IL
| | - Amir H. Dorafshar
- Division of Plastic and Reconstructive Surgery, Rush University Medical Center, Chicago, IL
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Erivan R, Samper N, Villatte G, Boisgard S, Descamps S, Berger M. No Detectable Alteration of Inorganic Allogeneic Bone Matrix Colonizing Mesenchymal Cells: A Step Towards Personalized Bone Grafts. J Bone Metab 2021; 28:161-169. [PMID: 34130368 PMCID: PMC8206612 DOI: 10.11005/jbm.2021.28.2.161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Accepted: 03/22/2021] [Indexed: 11/13/2022] Open
Abstract
Background During major bone substance loss, secured allogeneic bone matrix (ABM) is normally utilized for bone repair. Here, we propose a method to colonize ABM using autologous mesenchymal cells (MCs) to improve their integration. Moreover, in this study, the consequences of in vitro colonization on MCs have been evaluated. Methods After in vitro propagation of MCs, their proliferation kinetics on ABM pre-coated with gelatin, fibronectin, collagen IV and human serum (HS) was monitored, and they were compared with cells cultured without ABM for 8 weeks. The effect of ABM on cell phenotype was also assessed. Lastly, the ability of ABM-colonizing MCs to perform hematopoiesis, a function normally preserved in selected culture conditions, and their differentiation towards osteoblastic lineage were evaluated. Results MC and colony-forming unit-fibroblast proliferated 930- and 590-fold, respectively. The proliferation rate of the expanded MCs was higher, forming a 3-dimensional structure in all ABMs. Pre-coating with HS was the most efficient treatment of ABMs to increase the initial adherence of MCs, and it partly explains the reason for the higher propagation of MCs. Flow cytometry analyses revealed subtle alterations in ABM-colonizing cells; however, the ability of MCs to maintain long-term culture initiating cells proliferation and differentiate into osteoblastic lineage was preserved. Conclusions In this study, the in vitro biocompatibility of bone marrow (BM) MCs with ABMs, the role of HS in scaffold coating, and the possibility of initially using a small BM sample for this approach were demonstrated.
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Affiliation(s)
- Roger Erivan
- Université Clermont Auvergne, CHU Clermont-Ferrand, CNRS, SIGMA Clermont, ICCF, Clermont-Ferrand, France.,Department of Orthopedic and Trauma Surgery, Hôpital Gabriel Montpied, CHU de Clermont Ferrand, Clermont-Ferrand, France
| | - Nicolas Samper
- Université Clermont Auvergne, CHU Clermont-Ferrand, Clermont, Clermont- Ferrand, France
| | - Guillaume Villatte
- Université Clermont Auvergne, CHU Clermont-Ferrand, CNRS, SIGMA Clermont, ICCF, Clermont-Ferrand, France
| | - Stéphane Boisgard
- Université Clermont Auvergne, CHU Clermont-Ferrand, CNRS, SIGMA Clermont, ICCF, Clermont-Ferrand, France
| | - Stéphane Descamps
- Université Clermont Auvergne, CHU Clermont-Ferrand, CNRS, SIGMA Clermont, ICCF, Clermont-Ferrand, France
| | - Marc Berger
- Université Clermont Auvergne, CHU Clermont-Ferrand, GECOM, CRB Auvergne, Clermont-Ferrand, France
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Mancuso E, Shah L, Jindal S, Serenelli C, Tsikriteas ZM, Khanbareh H, Tirella A. Additively manufactured BaTiO 3 composite scaffolds: A novel strategy for load bearing bone tissue engineering applications. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 126:112192. [PMID: 34082989 DOI: 10.1016/j.msec.2021.112192] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 05/09/2021] [Accepted: 05/14/2021] [Indexed: 02/07/2023]
Abstract
Piezoelectric ceramics, such as BaTiO3, have gained considerable attention in bone tissue engineering applications thanks to their biocompatibility, ability to sustain a charged surface as well as improve bone cells' adhesion and proliferation. However, the poor processability and brittleness of these materials hinder the fabrication of three-dimensional scaffolds for load bearing tissue engineering applications. For the first time, this study focused on the fabrication and characterisation of BaTiO3 composite scaffolds by using a multi-material 3D printing technology. Polycaprolactone (PCL) was selected and used as dispersion phase for its low melting point, easy processability and wide adoption in bone tissue engineering. The proposed single-step extrusion-based strategy enabled a faster and solvent-free process, where raw materials in powder forms were mechanically mixed and subsequently fed into the 3D printing system for further processing. PCL, PCL/hydroxyapatite and PCL/BaTiO3 composite scaffolds were successfully produced with high level of consistency and an inner architecture made of seamlessly integrated layers. The inclusion of BaTiO3 ceramic particles (10% wt.) significantly improved the mechanical performance of the scaffolds (54 ± 0.5 MPa) compared to PCL/hydroxyapatite scaffolds (40.4 ± 0.1 MPa); moreover, the presence of BaTiO3 increased the dielectric permittivity over the entire frequency spectrum and tested temperatures. Human osteoblasts Saos-2 were seeded on scaffolds and cellular adhesion, proliferation, differentiation and deposition of bone-like extracellular matrix were evaluated. All tested scaffolds (PCL, PCL/hydroxyapatite and PCL/BaTiO3) supported cell growth and viability, preserving the characteristic cellular osteoblastic phenotype morphology, with PCL/BaTiO3 composite scaffolds exhibiting higher mineralisation (ALP activity) and deposited bone-like extracellular matrix (osteocalcin and collagen I). The single-step multi-material additive manufacturing technology used for the fabrication of electroactive PCL/BaTiO3 composite scaffolds holds great promise for sustainability (reduced material waste and manufacturing costs) and it importantly suggests PCL/BaTiO3 scaffolds as promising candidates for load bearing bone tissue engineering applications to solve unmet clinical needs.
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Affiliation(s)
- Elena Mancuso
- Nanotechnology and Integrated Bio-Engineering Centre (NIBEC), Ulster University, Shore Road, BT37 0QB Newtownabbey, United Kingdom.
| | - Lekha Shah
- Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health (FMBH), University of Manchester, Oxford Road, M13 9PT Manchester, United Kingdom
| | - Swati Jindal
- Nanotechnology and Integrated Bio-Engineering Centre (NIBEC), Ulster University, Shore Road, BT37 0QB Newtownabbey, United Kingdom
| | - Cecile Serenelli
- Nanotechnology and Integrated Bio-Engineering Centre (NIBEC), Ulster University, Shore Road, BT37 0QB Newtownabbey, United Kingdom
| | | | - Hamideh Khanbareh
- Department of Mechanical Engineering, University of Bath, BA2 7AY Bath, United Kingdom
| | - Annalisa Tirella
- Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health (FMBH), University of Manchester, Oxford Road, M13 9PT Manchester, United Kingdom.
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Yue J, Guo X, Wang R, Li B, Sun Q, Liu W, Chen J, Li Y. Single approach to double-channel core decompression and bone grafting with structural bone support for treating osteonecrosis of the femoral head in different stages. J Orthop Surg Res 2020; 15:198. [PMID: 32471465 PMCID: PMC7260834 DOI: 10.1186/s13018-020-01717-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 05/20/2020] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND We created a novel method-single approach to double-channel core decompression and bone grafting with structural bone support (SDBS)-to treat early-stage osteonecrosis of the femoral head (ONFH) by improving the Phemister technique. This study aimed to evaluate the results of SDBS for early-stage ONFH. METHODS Altogether, 53 patients (73 hips) were treated using SDBS during 2016-2018. Bilateral (20 patients) and unilateral (33 patients = 18 left hips, 15 right hips) ONFH was diagnosed. According to the Association Research Circulation Osseous classification stages, the femoral heads were staged as IIB (n = 15), IIC (n = 19), IIIA (n = 34), IIIB (n = 4), and IIIC (n = 1). The Harris hip score was used to evaluate the hips' clinical function, computed tomography to evaluate subchondral fractures, and plain radiography to assess the extent of femoral head collapse. RESULTS The average follow-up was 20.71 ± 6.65 months (6-36 months). At the patients' last follow-up, 4 hips were found to require arthroplasty. Thus, the overall femoral head survival rate was 94.52% (69/73). Also, the overall Harris score (84.44 ± 14.57) was significantly higher than that preoperatively (77.67 ± 14.37) (P = 0.000). The combined excellent and good rate (76.71%) was significantly higher than that preoperatively (38.36%) (P = 0.000). Imaging showed that 16 femoral heads had some ONFH progression. The average length of stay was 6.15 ± 0.86 days. The average incision measured 2.69 ± 0.30 cm. Intraoperative blood loss was 61.20 ± 4.81 ml. There were no complications during or after the operation. CONCLUSION SDBS is an effective method for treating early-stage ONFH. It is a hip-preserving surgical approach to slow/prevent ONFH progression.
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Affiliation(s)
- Ju'an Yue
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
| | - Xiaozhong Guo
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China.
| | - Randong Wang
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
| | - Bing Li
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
| | - Qiang Sun
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
| | - Wangyan Liu
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
| | - Jiao Chen
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
| | - Yingnan Li
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
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Zhao H, Tang J, Zhou D, Weng Y, Qin W, Liu C, Lv S, Wang W, Zhao X. Electrospun Icariin-Loaded Core-Shell Collagen, Polycaprolactone, Hydroxyapatite Composite Scaffolds for the Repair of Rabbit Tibia Bone Defects. Int J Nanomedicine 2020; 15:3039-3056. [PMID: 32431500 PMCID: PMC7200251 DOI: 10.2147/ijn.s238800] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 04/08/2020] [Indexed: 12/21/2022] Open
Abstract
Background Electrospinning is a widely used technology that can produce scaffolds with high porosity and surface area for bone regeneration. However, the small pore sizes in electrospun scaffolds constrain cell growth and tissue-ingrowth. In this study, novel drug-loading core-shell scaffolds were fabricated via electrospinning and freeze drying to facilitate the repair of tibia bone defects in rabbit models. Materials and Methods The collagen core scaffolds were freeze-dried containing icariin (ICA)-loaded chitosan microspheres. The shell scaffolds were electrospun using collagen, polycaprolactone and hydroxyapatite materials to form CPH composite scaffolds with the ones containing ICA microspheres named CPHI. The core-shell scaffolds were then cross-linked by genipin. The morphology, microstructure, physical and mechanical properties of the scaffolds were assessed. Rat marrow mesenchymal stem cells from the wistar rat were cultured with the scaffolds. The cell adhesion and proliferation were analysed. Adult rabbit models with tibial plateau defects were used to evaluate the performance of these scaffolds in repairing the bone defects over 4 to 12 weeks. Results The results reveal that the novel drug-loading core-shell scaffolds were successfully fabricated, which showed good physical and chemical properties and appropriate mechanical properties. Furthermore, excellent cells attachment was observed on the CPHI scaffolds. The results from radiography, micro-computed tomography, histological and immunohistochemical analysis demonstrated that abundant new bones were formed on the CPHI scaffolds. Conclusion These new core-shell composite scaffolds have great potential for bone tissue engineering applications and may lead to effective bone regeneration and repair.
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Affiliation(s)
- Hongbin Zhao
- Medical Research Centre, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou 213164, People's Republic of China
| | - Junjie Tang
- Medical Research Centre, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou 213164, People's Republic of China
| | - Dong Zhou
- Medical Research Centre, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou 213164, People's Republic of China
| | - Yiping Weng
- Medical Research Centre, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou 213164, People's Republic of China
| | - Wen Qin
- Medical Research Centre, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou 213164, People's Republic of China
| | - Chun Liu
- Medical Research Centre, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou 213164, People's Republic of China
| | - Songwei Lv
- School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou 213164, People's Republic of China
| | - Wei Wang
- Medical School, Hexi University, Zhangye 730041, People's Republic of China
| | - Xiubo Zhao
- School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou 213164, People's Republic of China.,Department of Chemical and Biological Engineering, University of Sheffield, Sheffield S1 3JD, UK
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Zhang H, Jiao J, Jin H. Degradable poly-L-lysine-modified PLGA cell microcarriers with excellent antibacterial and osteogenic activity. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2019; 47:2391-2404. [PMID: 31184220 DOI: 10.1080/21691401.2019.1623230] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The surface modification of polymeric materials has become critical for improving the bone repair capability of materials. In this study, we used a poly-L-lysine (PLL) coating method to prepare functional poly (lactic acid-glycolic acid) (PLGA) cell microcarriers, and bone morphogenetic protein 7 (BMP-7) and ponericin G1 were immobilized on the surface of microcarriers. The scanning electron microscopy (SEM), water contact angle measurement, and energy-dispersive X-ray spectroscopy (EDX) was used to analyse the surface morphology of PLL-modified PLGA microcarriers (PLL@PLGA) and their ability to promote mineralization. At the same time, the growth factor binding efficiency and antimicrobial activity of the microcarriers were studied. The effects of microcarriers on cell behaviors were evaluated by cultivating MC3T3-E1 cells on different microcarriers. The results showed that the hydrophilicity, protein adsorption, and mineralization induction capability of the microcarriers were significantly improved by PLL surface modification. The biological experiments revealed that BMP-7 and ponericin G1 immobilized-PLL modified microcarriers can effectively inhibit the proliferation of pathogenic microorganisms while enhancing the ability of the microcarriers to promote cell proliferation and osteogenesis differentiation. Therefore, we believe that PLL-modified PLGA cell microcarriers loaded with BMP-7 and ponericin G1 (PLL@PLGA/BMP-7/ponericin G1) have great potential in the field of bone repair.
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Affiliation(s)
- Hanyang Zhang
- a Department of Orthopedic Surgery, The Second Hospital of Jilin University , Changchun , PR China
| | - Jianhang Jiao
- a Department of Orthopedic Surgery, The Second Hospital of Jilin University , Changchun , PR China
| | - Hui Jin
- a Department of Orthopedic Surgery, The Second Hospital of Jilin University , Changchun , PR China
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Dilogo IH, Phedy P, Kholinne E, Djaja YP, Fiolin J, Kusnadi Y, Yulisa ND. Autologous mesenchymal stem cell implantation, hydroxyapatite, bone morphogenetic protein-2, and internal fixation for treating critical-sized defects: a translational study. INTERNATIONAL ORTHOPAEDICS 2019; 43:1509-1519. [PMID: 30747273 PMCID: PMC6525135 DOI: 10.1007/s00264-019-04307-z] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Accepted: 01/27/2019] [Indexed: 01/10/2023]
Abstract
INTRODUCTION Critical-sized defect (CSD) is one of the most challenging cases for orthopaedic surgeons. We aim to explore the therapeutic potential of the combination of bone marrow-derived mesenchymal stem cells (BM-MSCs), hydroxyapatite (HA) granules, bone morphogenetic protein-2 (BMP-2), and internal fixation for treating CSDs. METHODS This was a translational study performed during the period of January 2012 to 2016. Subjects were patients diagnosed with CSDs who had previously failed surgical attempts. They were treated with the combination of autologous BM-MSCs, HA granules, BMP-2, and mechanical stabilization. Post-operative pain level, functional outcome, defect volume, and radiological healing were evaluated after a minimum follow-up of 12 months. RESULTS A total of six subjects were recruited in this study. The pain was significantly reduced in all cases; with the decrease of mean preoperative visual analog scale (VAS) from 4 ± 2.2 to 0 after six month follow-up. Clinical functional outcome percentage increased significantly from 25 ± 13.7 to 70.79 ± 19.5. Radiological healing assessment using Tiedemann score also showed an increase from 0.16 ± 0.4 to 8 ± 3 at one year follow-up. No immunologic nor neoplastic side effects were found. CONCLUSIONS The combination of autologous BM-MSCs, HA granules, and BMP-2 is safe and remains to be a good option for the definitive treatment for CSD with previous failed surgical attempts. Further studies with a larger sample size are required to be done.
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Affiliation(s)
- Ismail Hadisoebroto Dilogo
- Department of Orthopaedics and Traumatology, Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.
- Stem Cells Medical Technology Integrated Service Unit, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
- Stem Cells and Tissue Engineering Research Cluster, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.
| | - Phedy Phedy
- Department of Orthopaedics and Traumatology, Fatmawati General Hospital, Jakarta, Indonesia
| | - Erica Kholinne
- Department of Orthopaedics and Traumatology, St. Carolus Hospital, Jakarta, Indonesia
| | - Yoshi Pratama Djaja
- Department of Orthopaedics and Traumatology, Fatmawati General Hospital, Jakarta, Indonesia
| | - Jessica Fiolin
- Department of Orthopaedics and Traumatology, Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Yuyus Kusnadi
- Laboratory of Regenerative and Cellular Therapy (ReGeniC), Bifarma Adiluhung Ltd., Jakarta, Indonesia
| | - Nyimas Diana Yulisa
- Department of Radiology, Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
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Chen L, Shao L, Wang F, Huang Y, Gao F. Enhancement in sustained release of antimicrobial peptide and BMP-2 from degradable three dimensional-printed PLGA scaffold for bone regeneration. RSC Adv 2019; 9:10494-10507. [PMID: 35515290 PMCID: PMC9062520 DOI: 10.1039/c8ra08788a] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Accepted: 03/26/2019] [Indexed: 11/24/2022] Open
Abstract
One of the goals of bone tissue engineering is to create scaffolds with well-defined, inter-connected pores, excellent biocompatibility and osteoinductive ability. Three-dimensional (3D)-printed polymer scaffold coated with bioactive peptide are an effective approach to fabricating ideal bone tissue engineering scaffolds for bone defect repair. However, the current strategy of adding bioactive peptides generally cause degradation to the polymer materials or damage the bioactivity of the biomolecules. Thus, in this study, we used a biomimetic process via poly(dopamine) coating to prepare functional 3D PLGA porous scaffolds with immobilized BMP-2 and ponericin G1 that efficiently regulate the osteogenic differentiation of preosteoblasts (MC3T3-E1) and simultaneously inhibit of pathogenic microbes, thereby enhancing biological activity. In this study, we analysed a 3D PLGA porous scaffold by scanning electron microscopy, water contact angle measurements, and materials testing. Subsequently, we examined the adsorption, release and in vitro antimicrobial activity of the 3D PLGA. Surface characterization showed that poly(dopamine) surface modification could more efficiently mediate the immobilization of BMP-2 and ponericin G1 onto the scaffold surfaces than physical adsorption, and that ponericin G1-immobilized 3D PLGA scaffolds were able to maintain long-term antibacterial activity. We evaluated the influence on cell adhesion, proliferation and differentiation by culturing MC3T3-E1 cells on different modified 3D PLGA scaffolds in vitro. The biological results indicate that MC3T3-E1 cell attachment and proliferation on BMP-2/ponericin G1-immobilized 3D PLGA scaffolds were much higher than those on other groups. Calcium deposition, and gene expression results showed that the osteogenic differentiation of cells was effectively improved by loading the 3D PLGA scaffold with BMP-2 and ponericin G1. In summary, our findings indicated that the polydopamine-assisted surface modification method can be a useful tool for grafting biomolecules onto biodegradable implants, and the dual release of BMP-2 and ponericin G1 can enhance the osteointegration of bone implants and simultaneously inhibit of pathogenic microbes. Therefore, we conclude that the BMP-2/ponericin G1-loaded PLGA 3D scaffolds are versatile and biocompatible scaffolds for bone tissue engineering. One of the goals of bone tissue engineering is to create scaffolds with well-defined, inter-connected pores, excellent biocompatibility and osteoinductive ability.![]()
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Affiliation(s)
- Lei Chen
- Department of Joints and Sports Medicine
- The First Hospital of Jilin University
- Changchun
- PR China
| | - Liping Shao
- Department of Joints and Sports Medicine
- The First Hospital of Jilin University
- Changchun
- PR China
| | - Fengping Wang
- Department of Joints and Sports Medicine
- The First Hospital of Jilin University
- Changchun
- PR China
| | - Yifan Huang
- Department of Joints Surgery
- The First Hospital of Jilin University
- Changchun
- PR China
| | - Fenghui Gao
- Department of Orthopedic
- The First Hospital of Jilin University
- Changchun
- PR China
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Dang M, Saunders L, Niu X, Fan Y, Ma PX. Biomimetic delivery of signals for bone tissue engineering. Bone Res 2018; 6:25. [PMID: 30181921 PMCID: PMC6115422 DOI: 10.1038/s41413-018-0025-8] [Citation(s) in RCA: 155] [Impact Index Per Article: 22.1] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2018] [Revised: 05/22/2018] [Accepted: 06/15/2018] [Indexed: 02/06/2023] Open
Abstract
Bone tissue engineering is an exciting approach to directly repair bone defects or engineer bone tissue for transplantation. Biomaterials play a pivotal role in providing a template and extracellular environment to support regenerative cells and promote tissue regeneration. A variety of signaling cues have been identified to regulate cellular activity, tissue development, and the healing process. Numerous studies and trials have shown the promise of tissue engineering, but successful translations of bone tissue engineering research into clinical applications have been limited, due in part to a lack of optimal delivery systems for these signals. Biomedical engineers are therefore highly motivated to develop biomimetic drug delivery systems, which benefit from mimicking signaling molecule release or presentation by the native extracellular matrix during development or the natural healing process. Engineered biomimetic drug delivery systems aim to provide control over the location, timing, and release kinetics of the signal molecules according to the drug's physiochemical properties and specific biological mechanisms. This article reviews biomimetic strategies in signaling delivery for bone tissue engineering, with a focus on delivery systems rather than specific molecules. Both fundamental considerations and specific design strategies are discussed with examples of recent research progress, demonstrating the significance and potential of biomimetic delivery systems for bone tissue engineering.
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Affiliation(s)
- Ming Dang
- Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI USA
| | - Laura Saunders
- Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI USA
| | - Xufeng Niu
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
- Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, China
| | - Yubo Fan
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
- Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, China
| | - Peter X. Ma
- Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI USA
- Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI USA
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI USA
- Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI USA
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16
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Three-Dimensional Radiological Assessment of Alveolar Bone Volume Preservation Using Bovine Bone Xenograft. J Craniofac Surg 2018; 29:e203-e209. [PMID: 29303859 DOI: 10.1097/scs.0000000000004263] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
INTRODUCTION Alveolar bone is critical in supporting natural teeth, dental implants as well as a removable and fixed prosthesis. Alveolar bone volume diminishes when its associated natural tooth is lost. OBJECTIVE The aim of this study is to evaluate the effectiveness of bovine bone granules on alveolar bone socket augmentation for ridge preservation following atraumatic tooth extraction. MATERIALS AND METHODS Twenty medically fit patients (12 males and 8 females aged between 18 and 40 years) who needed noncomplicated tooth extraction of 1 mandibular premolar tooth were divided randomly and equally into 2 groups. In control group I, the empty extraction socket was left untreated and allowed to heal in a conventional way. In group II, the empty extraction socket wound was filled with lyophilized bovine bone xenograft granules 0.25 to 1 mm of size, 1 mL/vial. A resorbable pericardium membrane was placed to cover the defect. Clinical and 3-dimensional radiological assessments were performed at day 0, 3 months, and 9 months postoperative. RESULTS There were no clinical differences in general wound healing between the groups. Comparisons within the groups showed a significant difference of bone resorption of 1.49 mm (95% confidence interval, 0.63-2.35) at 3 months, and further resorption of 1.84 mm (P ≤ 0.05) at 9 months in the control group. No significant changes of bone resorption were observed in group II during the same time interval. Comparison between groups showed a significant difference of bone resorption at 3 and 9 months (2.40 and 2.88 mm, respectively). CONCLUSION The use of lyophilized demineralized bovine bone granules in socket preservation to fill in the extraction socket seems essential in preserving the alveolar bone dimension as it showed excellent soft and hard tissue healing. This study concludes that the alveolar bone socket exhibited a dynamic process of resorption from the first day of tooth extraction. Evidence shows the possibility of using bovine bone granules routinely in socket volume preservation techniques following tooth extraction.
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Abstract
Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, these cells would compete with endogenous repair cells for limited oxygen and nutrients within ischaemic defects. Alternatively, it may be possible to employ extracellular vesicles (EVs) secreted by culture-expanded cells for overcoming key bottlenecks to endochondral repair, such as defect vascularization, chondrogenesis, and osseous remodelling. While mesenchymal stromal/stem cells are a promising source of therapeutic EVs, other donor cells should also be considered. The efficacy of an EV-based therapeutic will likely depend on the design of companion scaffolds for controlled delivery to specific target cells. Ultimately, the knowledge gained from studies of EVs could one day inform the long-term development of synthetic, engineered nanovesicles. In the meantime, EVs harnessed from in vitro cell culture have near-term promise for use in bone regenerative medicine. This narrative review presents a rationale for using EVs to improve the repair of large bone defects, highlights promising cell sources and likely therapeutic targets for directing repair through an endochondral pathway, and discusses current barriers to clinical translation. Cite this article: E. Ferreira, R. M. Porter. Harnessing extracellular vesicles to direct endochondral repair of large bone defects. Bone Joint Res 2018;7:263-273. DOI: 10.1302/2046-3758.74.BJR-2018-0006.
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Affiliation(s)
- E. Ferreira
- Departments of Internal Medicine and Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - R. M. Porter
- Departments of Internal Medicine and Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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Song J, Kim J, Woo HM, Yoon B, Park H, Park C, Kang BJ. Repair of rabbit radial bone defects using bone morphogenetic protein-2 combined with 3D porous silk fibroin/β-tricalcium phosphate hybrid scaffolds. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2018; 29:716-729. [DOI: 10.1080/09205063.2018.1438126] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Jaeyong Song
- College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Republic of Korea
| | - Junhyung Kim
- College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Republic of Korea
| | - Heung-Myung Woo
- College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Republic of Korea
| | - Byungil Yoon
- College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Republic of Korea
| | - Hyunjung Park
- Nano-Bio Regenerative Medical Institute, School of Medicine, Hallym University, Chuncheon, Republic of Korea
| | - Chanhum Park
- Nano-Bio Regenerative Medical Institute, School of Medicine, Hallym University, Chuncheon, Republic of Korea
| | - Byung-Jae Kang
- College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Republic of Korea
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Yorukoglu AC, Kiter AE, Akkaya S, Satiroglu-Tufan NL, Tufan AC. A Concise Review on the Use of Mesenchymal Stem Cells in Cell Sheet-Based Tissue Engineering with Special Emphasis on Bone Tissue Regeneration. Stem Cells Int 2017; 2017:2374161. [PMID: 29230248 PMCID: PMC5694585 DOI: 10.1155/2017/2374161] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Revised: 08/30/2017] [Accepted: 09/12/2017] [Indexed: 12/19/2022] Open
Abstract
The integration of stem cell technology and cell sheet engineering improved the potential use of cell sheet products in regenerative medicine. This review will discuss the use of mesenchymal stem cells (MSCs) in cell sheet-based tissue engineering. Besides their adhesiveness to plastic surfaces and their extensive differentiation potential in vitro, MSCs are easily accessible, expandable in vitro with acceptable genomic stability, and few ethical issues. With all these advantages, they are extremely well suited for cell sheet-based tissue engineering. This review will focus on the use of MSC sheets in osteogenic tissue engineering. Potential application techniques with or without scaffolds and/or grafts will be discussed. Finally, the importance of osteogenic induction of these MSC sheets in orthopaedic applications will be demonstrated.
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Affiliation(s)
- A. Cagdas Yorukoglu
- Department of Orthopaedics and Traumatology, School of Medicine, Pamukkale University, Denizli, Turkey
| | - A. Esat Kiter
- Department of Orthopaedics and Traumatology, School of Medicine, Pamukkale University, Denizli, Turkey
| | - Semih Akkaya
- Department of Orthopaedics and Traumatology, School of Medicine, Pamukkale University, Denizli, Turkey
| | - N. Lale Satiroglu-Tufan
- Department of Forensic Medicine, Forensic Genetics Laboratory, and Department of Pediatric Genetics, School of Medicine, Ankara University, Ankara, Turkey
| | - A. Cevik Tufan
- Department of Histology and Embryology, School of Medicine, Ankara Yıldırım Beyazıt University, Ankara, Turkey
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Imam MA, Holton J, Ernstbrunner L, Pepke W, Grubhofer F, Narvani A, Snow M. A systematic review of the clinical applications and complications of bone marrow aspirate concentrate in management of bone defects and nonunions. INTERNATIONAL ORTHOPAEDICS 2017; 41:2213-2220. [PMID: 28804813 DOI: 10.1007/s00264-017-3597-9] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Accepted: 07/31/2017] [Indexed: 12/12/2022]
Abstract
PURPOSE Fracture healing encompasses a succession of dynamic multifactorial metabolic events, which ultimately re-establishes the integrity of the biomechanical properties of the bone. Up to 10% of the fractures occurring annually will need additional surgical procedures because of impaired healing. The aim of this article is to review the current literature regarding the use of bone marrow aspirate concentrate (BMAC) and its effectiveness in the management of bone defects. METHODS We have included all published clinical literature investigating the development, techniques and applications of BMAC. Language, design and risk of bias did not deter the initial inclusion of any study. Our search was exclusively limited to studies involving human subjects. A PRISMA compliant search was carried out as published in 2009. This included the online databases: PubMed, EMBASE, clinical trial.gov and the Cochrane library from 1960 to the end of May 2015. MeSH terms used included: "Bone" AND "Marrow" AND "Aspirate" AND "Concentrate" AND "Bone Defects" AND "NONUNION". Eligible studies were independently appraised by two authors using the Critical Appraisal Skills Program checklist. For the purpose of narrative review, relevant studies were included irrespective of methodology or level of evidence. RESULTS Thirty-four of the 103 (48 PubMed and 55 EMBASE) results yielded by the preliminary search were included. Exclusions included three duplicate records, six letters, 17 non-orthopaedics related studies and four records irrelevant to our search topic. The CASP appraisal confirmed a satisfactory standard of 31 studies. They all had clearly defined objectives, were well designed and conducted appropriately to meet them. The published studies reported the use of BMAC in non-union and fracture healing (15 studies), bone defects (nine studies), spine fusion (two studies), distraction osteogensis (two studies) and complications related to the use of BMAC (seven studies). CONCLUSIONS Stem cells found in BMAC have the potential to self-renew, undertake clonal expansion and differentiate into different musculoskeletal tissues. The commercial processing of BMAC needs to be optimized in order to achieve a consistent end product, which will provide predicable and translatable results. The future potential of cell characterization in order to determine the optimum cell for repair/regeneration of bone also needs to be explored. LEVEL OF EVIDENCE Systematic Review of minimum level IV studies.
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Affiliation(s)
- Mohamed A Imam
- Department of Trauma and Orthopaedics, Faculty of Medicine, Suez Canal University, Circular road, Ismailia, Egypt.
- The Royal Orthopaedic Hospital, Birmingham, UK.
- Rowley Bristow Orthopaedic Centre, Ashford and St Peters Hospitals, Chertsey, UK.
| | - James Holton
- The Royal Orthopaedic Hospital, Birmingham, UK
- Birmingham University, Birmingham, UK
| | - Lukas Ernstbrunner
- Department of Orthopaedics, Balgrist University Hospital, University of Zurich, Forchstrasse 340, 8008, Zurich, Switzerland
- Department of Orthopaedics and TraumatologyParacelsus, Medical University, Muellner Hauptstrasse 48, 5020, Salzburg, Austria
| | - Wojciech Pepke
- Department of Orthopaedics, Universität Heidelberg, Heidelberg, Germany
| | - Florian Grubhofer
- Department of Orthopaedics, Balgrist University Hospital, University of Zurich, Forchstrasse 340, 8008, Zurich, Switzerland
| | - Ali Narvani
- Rowley Bristow Orthopaedic Centre, Ashford and St Peters Hospitals, Chertsey, UK
| | - Martyn Snow
- The Royal Orthopaedic Hospital, Birmingham, UK
- Birmingham University, Birmingham, UK
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Treatment of critical-sized bone defects: clinical and tissue engineering perspectives. EUROPEAN JOURNAL OF ORTHOPAEDIC SURGERY AND TRAUMATOLOGY 2017; 28:351-362. [PMID: 29080923 DOI: 10.1007/s00590-017-2063-0] [Citation(s) in RCA: 253] [Impact Index Per Article: 31.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Accepted: 10/08/2017] [Indexed: 12/11/2022]
Abstract
Critical-sized bone defects are defined as those that will not heal spontaneously within a patient's lifetime. Current treatment options include vascularized bone grafts, distraction osteogenesis, and the induced membrane technique. The induced membrane technique is an increasingly utilized method with favorable results including high rates of union. Tissue engineering holds promise in the treatment of large bone defects due to advancement of stem cell biology, novel biomaterials, and 3D bioprinting. In this review, we provide an overview of the current operative treatment strategies of critical-sized bone defects as well as the current state of tissue engineering for such defects.
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Rollo G, Vicenti G, Rotini R, Abate A, Colella A, D'Arienzo A, Carrozzo M, Moretti B. Clavicle aseptic nonunion: is there a place for cortical allogenic strut graft? Injury 2017; 48 Suppl 3:S60-S65. [PMID: 29025612 DOI: 10.1016/s0020-1383(17)30660-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
We investigated functional and radiological outcome in 57 cases of midshaft clavicle nonunion treated with open reduction and internal fixation with plate and screws over a 13 year-period. Intercalary bone graft was used in 42 patients; opposite autologous strut graft was used in 31 cases to provide mechanical support to the host bone. Patients were analysed using chart and radiological review and assessed with DASH questionnaire obtained at the latest follow-up. 37 patients were male while 20 were females, with a mean age of 35 years (63-17). All cases were of nonunion, 35 atrophic and 22 hypertrophic. The dominant side was injured in 32 cases and the non dominant in 25 cases. Primarily, 43 cases were treated conservatively with a figure of eight bandage. Time between fracture and our operative treatment was on average 44 months (13-72 months). Only those patients who were symptomatic were included in this study. We used straight reconstruction LCP and low profile precontoured plates. By reviewing patients charts all the cases but one of nonunion progressed to osseous healing at a mean time of 14 weeks (range 12-16). The patient with non-union refused further surgery. 49 patients were available for a final follow up. DASH score was 16.7 at an average of 42 months. Open surgery and internal fixation, using plate and screws in a compression construct is the treatment of choice for symptomatic clavicular non-unions. Intercalary autologous or allograft bone graft should be used especially in patient with significant bone loss; autologous cortical strut graft provides optimum mechanical stability, thus assuring optimal screw purchase and allowing immediate limb movement.
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Affiliation(s)
| | - Giovanni Vicenti
- Department of Neuroscience and Organs of Sense, Orthopedic Section, Faculty of Medicine and Surgery, University of Bari, Bari, Italy.
| | - Roberto Rotini
- Shoulder and Elbow Surgery, Rizzoli Orthopaedic Institute, Bologna, Italy
| | - Antonella Abate
- Department of Neuroscience and Organs of Sense, Orthopedic Section, Faculty of Medicine and Surgery, University of Bari, Bari, Italy
| | - Antonio Colella
- Department of Neuroscience and Organs of Sense, Orthopedic Section, Faculty of Medicine and Surgery, University of Bari, Bari, Italy
| | - Antonio D'Arienzo
- Orthopedic and Trauma Section, University of Palermo, Palermo, Italy
| | - Massimiliano Carrozzo
- Department of Neuroscience and Organs of Sense, Orthopedic Section, Faculty of Medicine and Surgery, University of Bari, Bari, Italy
| | - Biagio Moretti
- Department of Neuroscience and Organs of Sense, Orthopedic Section, Faculty of Medicine and Surgery, University of Bari, Bari, Italy
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Bayer EA, Jordan J, Roy A, Gottardi R, Fedorchak MV, Kumta PN, Little SR. * Programmed Platelet-Derived Growth Factor-BB and Bone Morphogenetic Protein-2 Delivery from a Hybrid Calcium Phosphate/Alginate Scaffold. Tissue Eng Part A 2017; 23:1382-1393. [PMID: 28537482 DOI: 10.1089/ten.tea.2017.0027] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Bone tissue engineering requires the upregulation of several regenerative stages, including a critical early phase of angiogenesis. Previous studies have suggested that a sequential delivery of platelet-derived growth factor (PDGF) to bone morphogenetic protein-2 (BMP-2) could promote angiogenic tubule formation when delivered to in vitro cocultures of human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs). However, it was previously unclear that this PDGF to BMP-2 delivery schedule will result in cell migration into the scaffolding system and affect the later expression of bone markers. Additionally, a controlled delivery system had not yet been engineered for programmed sequential presentation of this particular growth factor. By combining alginate matrices with calcium phosphate scaffolding, a programmed growth factor delivery schedule was achieved. Specifically, a combination of alginate microspheres, alginate hydrogels, and a novel blend of resorbable calcium phosphate-based cement (ReCaPP) was used. PDGF and BMP-2 were sequentially released from this hybrid calcium phosphate/alginate scaffold with the desired 3-day overlap in PDGF to BMP-2 delivery. Using a three-dimensional coculture model, we observed that this sequence of PDGF to BMP-2 delivery influenced both cellular infiltration and alkaline phosphatase (ALP) expression. It was found that the presence of early PDGF delivery increased the distance of cell infiltration into the calcium phosphate/alginate scaffolding in comparison to early BMP-2 delivery and simultaneous PDGF+BMP-2 delivery. It was also observed that hMSCs expressed a greater amount of ALP+ staining in response to scaffolds delivering the sequential PDGF to BMP-2 schedule, when compared with scaffolds delivering no growth factor, or PDGF alone. Importantly, hMSCs cultured with scaffolds releasing the PDGF to BMP-2 schedule showed similar amounts of ALP staining to hMSCs cultured with BMP-2 alone, suggesting that the sequential schedule of PDGF to BMP-2 presentation promotes differentiation of hMSCs toward an osteoblast phenotype while also increasing cellular infiltration of the scaffold.
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Affiliation(s)
- Emily A Bayer
- 1 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,2 The McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - Jahnelle Jordan
- 1 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - Abhijit Roy
- 1 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,2 The McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - Riccardo Gottardi
- 3 Department of Chemical Engineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,4 Department of Orthopedic Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.,5 Ri.MED Foundation , Palermo, Italy
| | - Morgan V Fedorchak
- 1 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,2 The McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.,3 Department of Chemical Engineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,6 Department of Ophthalmology, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - Prashant N Kumta
- 1 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,2 The McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.,3 Department of Chemical Engineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,7 Department of Mechanical Engineering and Materials Science, University of Pittsburgh , Pittsburgh, Pennsylvania.,8 Department of Oral Biology, Center for Craniofacial Regeneration, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - Steven R Little
- 1 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,2 The McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.,3 Department of Chemical Engineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,9 Department of Immunology, University of Pittsburgh , Pittsburgh, Pennsylvania
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Perna F, Pilla F, Nanni M, Berti L, Lullini G, Traina F, Faldini C. Two-stage surgical treatment for septic non-union of the forearm. World J Orthop 2017; 8:471-477. [PMID: 28660139 PMCID: PMC5478490 DOI: 10.5312/wjo.v8.i6.471] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Revised: 04/18/2017] [Accepted: 05/15/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the effectiveness of a two-stage surgical procedure for the treatment of septic forearm non-union.
METHODS Septic non-unions are rare complications of forearm fractures. When they occur, they modify the relationship between forearm bones leading to a severe functional impairment. Treatment is challenging and surgery and antibiotic therapy are required to achieve infection resolution. It is even harder to obtain non-union healing with good functional results. The aim of this study is to present a two stages surgical treatment for septic forearm non-union with revision and temporary stabilization of the non-union until infection has cleared and subsequently perform a new synthesis with plate, opposite bone graft strut and intercalary graft. We retrospectively reviewed 18 patients with a mean age at the time of primary injury of 34.5 years (19-57 years) and a mean follow-up of 6 years (2-10 years). All patients presented an atrophic non-union with a mean length of the bone defect of 1.8 cm (1.2-4 cm). Complications and clinical results after surgical treatment were recorded.
RESULTS Mean time to resolution of the infectious process was 8.2 wk (range 4-20 wk) after the first surgery and specific antibiotic therapy. All the non-union healed with an average time of 5 mo (range 2-10 mo) after the second step surgery. Cultures on intraoperative samples were positive in all cases. No major intraoperative complications occurred. Two patients developed minor complications and one needed a second surgical debridement for infection resolution. At the last follow-up functional results were excellent in 5 (27.8%) patients, satisfactory in 10 (55.5%) and unsatisfactory in 3 (16.7%) patients. No activities of daily living (ADLs) limitations were reported by 12 (66.6%) patients, slight by 3 (16.6%) and severe limitation by 3 (16.6%) patients. Mean visual analog scale at the last follow-up was 1 (0-3).
CONCLUSION The two-step technique has proven to be effective to achieve resolution of the infectious process and union with good functional results and low rate of complications.
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Zhou J, Guo X, Zheng Q, Wu Y, Cui F, Wu B. Improving osteogenesis of three-dimensional porous scaffold based on mineralized recombinant human-like collagen via mussel-inspired polydopamine and effective immobilization of BMP-2-derived peptide. Colloids Surf B Biointerfaces 2017; 152:124-132. [DOI: 10.1016/j.colsurfb.2016.12.041] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Revised: 12/04/2016] [Accepted: 12/30/2016] [Indexed: 11/15/2022]
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Xue D, Yu J, Zheng Q, Feng G, Li W, Pan Z, Wang J, Li H. The treatment strategies of intertrochanteric fractures nonunion: An experience of 23 nonunion patients. Injury 2017; 48:708-714. [PMID: 28139213 DOI: 10.1016/j.injury.2017.01.042] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Revised: 01/18/2017] [Accepted: 01/23/2017] [Indexed: 02/02/2023]
Abstract
BACKGROUND Intertrochanteric femoral fractures are common, but the nonunion of intertrochanteric fractures is not. The purpose of this study was to divide intertrochanteric fracture nonunion into different types and give corresponding treatment strategies. METHODS We retrospectively evaluated 23 patients with intertrochanteric fracture nonunion. The patients were divided into five groups and each group was treated with a different strategy. All patients had staged clinical and radiographic follow-ups and the mean follow-up was 16.0±4.6months. RESULTS Except for the patients treated with total hip arthroplasty, all patients achieved fracture union. The mean union time was 4.7±1.2months. The Harris hip function score differed significantly from preoperative (28.9±6.8) to postoperative (83.8±6.3; p<0.05). For the three patients who were classified as type III, the femoral neck shaft angle was corrected to a significant degree, from 97.3±6.4 to 127.3±2.5 (p<0.05). For the four patients who were classified as type V, the mean time from debridement to re-internal fixation was 3.7±1.5months. CONCLUSIONS There are several factors associated with the failure of intertrochanteric fracture treatments. We need to analyze the causes of fracture treatment failure carefully. Based on our five classifications and corresponding treatment strategies, the radiographic and functional treatment outcomes were satisfactory. Future larger comparative studies are needed to confirm our results.
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Affiliation(s)
- Deting Xue
- Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China.
| | - Jiawei Yu
- Department of Orthopaedics, Zhuji People's Hospital of Zhejiang Province, Shaoxing, 311800, Zhejiang, China.
| | - Qiang Zheng
- Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China.
| | - Gang Feng
- Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China.
| | - Weixu Li
- Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China.
| | - Zhijun Pan
- Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China.
| | - Jian Wang
- Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China.
| | - Hang Li
- Department of Orthopaedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China.
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Abstract
Treatment of nonunion has radically changed in recent years. We define nonunion as a fracture of bone induced either by trauma or surgery which does not show clinical or radiographic signs of progression to healing within a reasonable time span. The reparative processes are present but inadequate. Fracture healing may be considered to be a balance between repair and breakdown processes at the fracture site. When breakdown exceeds repair, nonunion is the result. Altering the conditions at the fracture site even marginally in favour of repair will eventually lead to bony continuity being restored. Nonunion treatment should follow three principles: a) realignment; b) stabilization; and c) stimulation. Any surgical proce dure should address one or all of these areas. In this article the principles of nonunion management are explained, together with different bone healing stimulation techniques and our clinical results.
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Affiliation(s)
- Ricardo J Pacheco
- Academic Unit of Orthopaedic and Traumatic Surgery, University of Sheffield, Sheffield, UK,
| | - Martin D Bradbury
- Academic Unit of Orthopaedic and Traumatic Surgery, University of Sheffield, Sheffield, UK
| | - Ata G Kasis
- Academic Unit of Orthopaedic and Traumatic Surgery, University of Sheffield, Sheffield, UK
| | - Michael Saleh
- Academic Unit of Orthopaedic and Traumatic Surgery, University of Sheffield, Sheffield, UK
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28
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Chieruzzi M, Pagano S, Moretti S, Pinna R, Milia E, Torre L, Eramo S. Nanomaterials for Tissue Engineering In Dentistry. NANOMATERIALS 2016; 6:nano6070134. [PMID: 28335262 PMCID: PMC5224610 DOI: 10.3390/nano6070134] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Revised: 07/04/2016] [Accepted: 07/18/2016] [Indexed: 02/08/2023]
Abstract
The tissue engineering (TE) of dental oral tissue is facing significant changes in clinical treatments in dentistry. TE is based on a stem cell, signaling molecule, and scaffold triad that must be known and calibrated with attention to specific sectors in dentistry. This review article shows a summary of micro- and nanomorphological characteristics of dental tissues, of stem cells available in the oral region, of signaling molecules usable in TE, and of scaffolds available to guide partial or total reconstruction of hard, soft, periodontal, and bone tissues. Some scaffoldless techniques used in TE are also presented. Then actual and future roles of nanotechnologies about TE in dentistry are presented.
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Affiliation(s)
- Manila Chieruzzi
- Department of Civil and Environmental Engineering-UdR INSTM-University of Perugia, Strada di Pentima, 4-05100 Terni, Italy.
| | - Stefano Pagano
- Department of Surgical and Biomedical Sciences-University of Perugia, S. Andrea delle Fratte, 06156 Perugia, Italy.
| | - Silvia Moretti
- Department of Experimental Medicine-University of Perugia Polo Unico Sant'Andrea delle Fratte, 06132 Perugia, Italy.
| | - Roberto Pinna
- Department of Biomedical Science-University of Sassari viale San Pietro 43/C -07100 Sassari, Italy.
| | - Egle Milia
- Department of Biomedical Science-University of Sassari viale San Pietro 43/C -07100 Sassari, Italy.
| | - Luigi Torre
- Department of Civil and Environmental Engineering-UdR INSTM-University of Perugia, Strada di Pentima, 4-05100 Terni, Italy.
| | - Stefano Eramo
- Department of Surgical and Biomedical Sciences-University of Perugia, S. Andrea delle Fratte, 06156 Perugia, Italy.
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Retrograde dynamic locked intramedullary nailing for aseptic supracondylar femoral nonunion after dynamic condylar screw treatment. EUROPEAN JOURNAL OF ORTHOPAEDIC SURGERY AND TRAUMATOLOGY 2016; 26:625-31. [PMID: 27314842 DOI: 10.1007/s00590-016-1800-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2016] [Accepted: 05/19/2016] [Indexed: 10/21/2022]
Abstract
OBJECTIVE Supracondylar femoral nonunions after dynamic condylar screw (DCS) treatment are uncommon, and few studies have addressed an optimal treatment technique for this disorder. Re-insertion of a new plate may not be secure because of bony defects in the distal fragment, created by the lag screw of the DCS. MATERIALS AND METHODS Forty-two consecutive adult patients with 42 supracondylar femoral nonunions were treated with removal of the DCS, re-alignment of the knee axis, and insertion of a retrograde dynamic traditional femoral locked nail. When necessary, a humeral plate was augmented to reinforce rotational stability. RESULTS A final group of 36 patients with 36 nonunions were followed for an average of 2.8 years (range 1.1-6.2 years). All nonunions healed with a union rate of 100 %, and the average time to union was 4.2 months (range 2.5-5.5 months). Complications included two malunions. There were no instances of nonunion or deep infection. Satisfactory knee function among 36 patients improved from 8.2 % preoperatively to 86.1 % at the last follow-up (p < 0.001). All 36 patients could walk without aids. CONCLUSION The described technique may be an excellent alternative treatment for an aseptic supracondylar femoral nonunion after DCS treatment. The technique is not difficult, and the union rate and satisfactory rate are high.
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30
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Novel Method for Loading Microporous Ceramics Bone Grafts by Using a Directional Flow. J Funct Biomater 2015; 6:1085-98. [PMID: 26703749 PMCID: PMC4695912 DOI: 10.3390/jfb6041085] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2015] [Revised: 12/08/2015] [Accepted: 12/16/2015] [Indexed: 11/17/2022] Open
Abstract
The aim of this study was the development of a process for filling the pores of a β-tricalcium phosphate ceramic with interconnected porosity with an alginate hydrogel. For filling of the ceramics, solutions of alginate hydrogel precursors with suitable viscosity were chosen as determined by rheometry. For loading of the porous ceramics with the gel the samples were placed at the flow chamber and sealed with silicone seals. By using a vacuum induced directional flow, the samples were loaded with alginate solutions. The loading success was controlled by ESEM and fluorescence imaging using a fluorescent dye (FITC) for staining of the gel. After loading of the pores, the alginate is transformed into a hydrogel through crosslinking with CaCl₂ solution. The biocompatibility of the obtained composite material was tested with a live dead cell staining by using MG-63 Cells. The loading procedure via vacuum assisted directional flow allowed complete filling of the pores of the ceramics within a few minutes (10 ± 3 min) while loading through simple immersion into the polymer solution or through a conventional vacuum method only gave incomplete filling.
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31
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Yang J, Zhu B, Fu K, Yang Q. The long-term outcomes following the use of inactivated autograft in the treatment of primary malignant musculoskeletal tumor. J Orthop Surg Res 2015; 10:177. [PMID: 26577680 PMCID: PMC4650863 DOI: 10.1186/s13018-015-0324-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2015] [Accepted: 11/12/2015] [Indexed: 12/17/2022] Open
Abstract
Background Biological reconstruction surgery is a tough but alluring option for treating primary malignant musculoskeletal tumors. In this article, we evaluate the clinical outcomes of primary malignant musculoskeletal tumors treated with inactivated autograft using alcohol. Method In this article, we include 58 patients who had primary malignant bone tumors treated with wide resection and recycling autograft reconstruction using alcohol between January 2003 and January 2013. The outcomes were measured by recurrence, functional status, and complications. Functional status was assessed according to the Musculoskeletal Tumor Society Score (MSTSS). The Kaplan-Meier survival curve was used to evaluate the survival rate of the patient. Result The most common tumor was osteosarcoma (31 cases) followed by chondrosarcoma (10 cases). The tibia was the most frequently involved skeletal site (27 cases) followed by femur (26 cases). The median follow-up period was 54 months, ranging from 18 to 96 months. In 58 patients, 12 were with local recurrence (20.7 %), 16 with lung metastasis (27.6 %), and 13 with complications (22.4 %). The main complication was infection (8 cases). The autografts survived in 49 patients (84.5 %). The mean MSTSS score was 78.5 %, ranging from 47 to 98 %. Conclusion Recycling autograft reconstruction using alcohol had favorable clinical outcomes to some degree; however, the recurrence and complication rates seem to be high. Thus, we should apply this method with caution and choose the patients with strict surgical indication.
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Affiliation(s)
- Jielai Yang
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
| | - Bin Zhu
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
| | - Kai Fu
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
| | - Qingcheng Yang
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
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König MA, Canepa DD, Cadosch D, Casanova E, Heinzelmann M, Rittirsch D, Plecko M, Hemmi S, Simmen HP, Cinelli P, Wanner GA. Direct transplantation of native pericytes from adipose tissue: A new perspective to stimulate healing in critical size bone defects. Cytotherapy 2015; 18:41-52. [PMID: 26563474 DOI: 10.1016/j.jcyt.2015.10.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Revised: 09/22/2015] [Accepted: 10/02/2015] [Indexed: 12/31/2022]
Abstract
BACKGROUND AIMS Fractures with a critical size bone defect (e.g., open fracture with segmental bone loss) are associated with high rates of delayed union and non-union. The prevention and treatment of these complications remain a serious issue in trauma and orthopaedic surgery. Autologous cancellous bone grafting is a well-established and widely used technique. However, it has drawbacks related to availability, increased morbidity and insufficient efficacy. Mesenchymal stromal cells can potentially be used to improve fracture healing. In particular, human fat tissue has been identified as a good source of multilineage adipose-derived stem cells, which can be differentiated into osteoblasts. The main issue is that mesenchymal stromal cells are a heterogeneous population of progenitors and lineage-committed cells harboring a broad range of regenerative properties. This heterogeneity is also mirrored in the differentiation potential of these cells. In the present study, we sought to test the possibility to enrich defined subpopulations of stem/progenitor cells for direct therapeutic application without requiring an in vitro expansion. METHODS We enriched a CD146+NG2+CD45- population of pericytes from freshly isolated stromal vascular fraction from mouse fat tissue and tested their osteogenic differentiation capacity in vitro and in vivo in a mouse model for critical size bone injury. RESULTS Our results confirm the ability of enriched CD146+NG2+CD45- cells to efficiently generate osteoblasts in vitro, to colonize cancellous bone scaffolds and to successfully contribute to regeneration of large bone defects in vivo. CONCLUSIONS This study represents proof of principle for the direct use of enriched populations of cells with stem/progenitor identity for therapeutic applications.
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Affiliation(s)
- Matthias A König
- Division of Trauma Surgery, Center for Clinical Research, University Hospital Zurich, University of Zurich, Sternwartstrasse 14, CH-8091 Zurich, Switzerland
| | - Daisy D Canepa
- Division of Trauma Surgery, Center for Clinical Research, University Hospital Zurich, University of Zurich, Sternwartstrasse 14, CH-8091 Zurich, Switzerland
| | - Dieter Cadosch
- Division of Trauma Surgery, Center for Clinical Research, University Hospital Zurich, University of Zurich, Sternwartstrasse 14, CH-8091 Zurich, Switzerland
| | - Elisa Casanova
- Division of Trauma Surgery, Center for Clinical Research, University Hospital Zurich, University of Zurich, Sternwartstrasse 14, CH-8091 Zurich, Switzerland
| | | | - Daniel Rittirsch
- Division of Trauma Surgery, Center for Clinical Research, University Hospital Zurich, University of Zurich, Sternwartstrasse 14, CH-8091 Zurich, Switzerland
| | - Michael Plecko
- Trauma Hospital Graz, Göstinger Strasse 24, A-8020 Graz, Austria
| | - Sonja Hemmi
- Division of Trauma Surgery, Center for Clinical Research, University Hospital Zurich, University of Zurich, Sternwartstrasse 14, CH-8091 Zurich, Switzerland
| | - Hans-Peter Simmen
- Division of Trauma Surgery, Center for Clinical Research, University Hospital Zurich, University of Zurich, Sternwartstrasse 14, CH-8091 Zurich, Switzerland
| | - Paolo Cinelli
- Division of Trauma Surgery, Center for Clinical Research, University Hospital Zurich, University of Zurich, Sternwartstrasse 14, CH-8091 Zurich, Switzerland.
| | - Guido A Wanner
- Division of Trauma Surgery, Center for Clinical Research, University Hospital Zurich, University of Zurich, Sternwartstrasse 14, CH-8091 Zurich, Switzerland.
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Kim JB, Lee DY, Seo SG, Kim EJ, Kim JH, Yoo WJ, Cho TJ, Choi IH. Demineralized Bone Matrix Injection in Consolidation Phase Enhances Bone Regeneration in Distraction Osteogenesis via Endochondral Bone Formation. Clin Orthop Surg 2015; 7:383-91. [PMID: 26330963 PMCID: PMC4553289 DOI: 10.4055/cios.2015.7.3.383] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Accepted: 03/23/2015] [Indexed: 11/06/2022] Open
Abstract
Background Distraction osteogenesis (DO) is a promising tool for bone and tissue regeneration. However, prolonged healing time remains a major problem. Various materials including cells, cytokines, and growth factors have been used in an attempt to enhance bone formation. We examined the effect of percutaneous injection of demineralized bone matrix (DBM) during the consolidation phase on bone regeneration after distraction. Methods The immature rabbit tibial DO model (20 mm length-gain) was used. Twenty-eight animals received DBM 100 mg percutaneously at the end of distraction. Another 22 animals were left without further procedure (control). Plain radiographs were taken every week. Postmortem bone dual-energy X-ray absorptiometry and micro-computed tomography (micro-CT) studies were performed at the third and sixth weeks of the consolidation period and histological analysis was performed. Results The regenerate bone mineral density was higher in the DBM group when compared with that in the saline injection control group at the third week postdistraction. Quantitative analysis using micro-CT revealed larger trabecular bone volume, higher trabecular number, and less trabecular separation in the DBM group than in the saline injection control group. Cross-sectional area and cortical thickness at the sixth week postdistraction, assessed using micro-CT, were greater in the regenerates of the DBM group compared with the control group. Histological evaluation revealed higher trabecular bone volume and trabecular number in the regenerate of the DBM group. New bone formation was apparently enhanced, via endochondral ossification, at the site and in the vicinity of the injected DBM. DBM was absorbed slowly, but it remained until the sixth postoperative week after injection. Conclusions DBM administration into the distraction gap at the end of the distraction period resulted in a significantly greater regenerate bone area, trabecular number, and cortical thickness in the rabbit tibial DO model. These data suggest that percutaneous DBM administration at the end of the distraction period or in the early consolidation period may stimulate regenerate bone formation and consolidation in a clinical situation with delayed bone healing during DO.
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Affiliation(s)
- Ji-Beom Kim
- Department of Orthopedic Surgery, Seoul National University Hospital, Seoul, Korea
| | - Dong Yeon Lee
- Department of Orthopedic Surgery, Seoul National University Hospital, Seoul, Korea
| | - Sang Gyo Seo
- Department of Orthopedic Surgery, Seoul National University Hospital, Seoul, Korea
| | - Eo Jin Kim
- Department of Orthopedic Surgery, Seoul National University Hospital, Seoul, Korea
| | - Ji Hye Kim
- Department of Orthopedic Surgery, Seoul National University Hospital, Seoul, Korea
| | - Won Joon Yoo
- Department of Orthopedic Surgery, Seoul National University Hospital, Seoul, Korea
| | - Tae-Joon Cho
- Department of Orthopedic Surgery, Seoul National University Hospital, Seoul, Korea
| | - In Ho Choi
- Department of Orthopedic Surgery, Seoul National University Hospital, Seoul, Korea
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Guzel Y, Karalezli N, Bilge O, Kacira BK, Esen H, Karadag H, Toker S, Göncü RG, Doral MN. The biomechanical and histological effects of platelet-rich plasma on fracture healing. Knee Surg Sports Traumatol Arthrosc 2015; 23:1378-1383. [PMID: 24170188 DOI: 10.1007/s00167-013-2734-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2013] [Accepted: 10/14/2013] [Indexed: 02/01/2023]
Abstract
PURPOSE Platelet-rich plasma (PRP) includes growth factors and proteins that accelerate and stimulate bone regeneration and tissue recovery. The aim of this study was to evaluate the effects of PRP on fracture healing in terms of biomechanics and histology. METHODS Seventy female rats were included in this experimental study. They were divided into three groups: Group I (no PRP, n = 30), Group II (PRP added, n = 30) and Group III (control, n = 10). The left femurs of the rats in Groups I and II were osteotomized and fixed by K-wires. Although no additional intervention was performed on Group I rats, PRP was applied to the fracture sites of Group II rats. The remaining ten rats were used as the control group of the biomechanical test (Group III). In the fourth week, nine femurs from Group I and ten femurs from Group II, and in the ninth week, nine femurs from each group were removed, and bone recovery was assessed histologically according to Modified Lane-Sandhu histological scoring criteria. Three-point bending test was applied to femurs for biomechanical evaluation in the ninth week. RESULTS Histological healing was found to be significantly higher in Group II than in Group I (p < 0.05). Furthermore, biomechanical test results showed that healing quantity and bone strength were significantly better in Group II than in Group I (p < 0.05). CONCLUSION PRP is a widely studied material in the physiology of fracture healing. The results of this study demonstrated the ameliorative biomechanical effects of PRP on fracture healing, in addition to accelerating the histological union of fractures. In the light of these results, PRP could be a viable alternative to accelerate the healing of fractures, late unions or non-unions. LEVEL OF EVIDENCE Prospective comparative study, Level II.
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Affiliation(s)
- Yunus Guzel
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Ordu University, Ordu, Turkey.
| | - Nazım Karalezli
- Department of Orthopaedics and Traumatology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Onur Bilge
- Department of Orthopaedics and Traumatology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Burkay K Kacira
- Department of Orthopaedics and Traumatology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Hasan Esen
- Department of Pathology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Hakan Karadag
- Department of Mechanical Engineering, Faculty of Mechanical Engineering, Necmettin Erbakan University, Konya, Turkey
| | - Serdar Toker
- Department of Orthopaedics and Traumatology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Recep Gani Göncü
- Department of Orthopaedics and Traumatology, Government Hospital of Beyhekim, Konya, Turkey
| | - Mahmut Nedim Doral
- Department of Orthopaedics and Traumatology, Hacettepe Faculty of Medicine, Hacettepe University, Ankara, Turkey
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Faldini C, Traina F, Perna F, Borghi R, Nanni M, Chehrassan M. Surgical treatment of aseptic forearm nonunion with plate and opposite bone graft strut. Autograft or allograft? INTERNATIONAL ORTHOPAEDICS 2015; 39:1343-9. [PMID: 25776465 DOI: 10.1007/s00264-015-2718-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Accepted: 02/16/2015] [Indexed: 02/07/2023]
Abstract
PURPOSE OF THE STUDY Adequate treatment of forearm nonunion should achieve both biological stimulation of the bone and mechanical stability. The use of bone graft could enhance the healing of a nonunion providing osteogenic, osteoconductive and osteoinductive stimulation and an optimal stability of the fixation. We retrospectively reviewed two cohorts of patients affected by forearm nonunion and treated with plate and opposite bone graft to determine whether the use of autograft versus allograft differs in terms of (1) rate of healing of the nonunion and (2) time of healing. MATERIALS AND METHODS Thirty-four patients were treated for aseptic forearm nonunion with cortical graft strut with opposite plate and intercalary graft in case of segmental bone defect. In 20 patients an autograft harvest from the fibula (group A) and in 14 (group B) an allograft provided by the bone bank of our institution were used. RESULTS All the nonunions healed in a mean of four months in both groups, ranging from two to 12 months in group A and from three to ten months in group B. At the latest follow up forearm function and pain were satisfactory in both groups. CONCLUSION The use of plate and opposite bone graft demonstrated to be effective in promoting the healing of forearm nonunions, without significant differences in terms of rate and time of healing in the two groups. Considering the higher surgical time and the comorbidity of the donor site, if a bone bank is available, we suggest to use homologous cortical bone strut graft with opposite plate and screw fixation for the treatment of aseptic forearm nonunion rather than autograft.
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Zavatti M, Bertoni L, Maraldi T, Resca E, Beretti F, Guida M, La Sala GB, De Pol A. Critical-size bone defect repair using amniotic fluid stem cell/collagen constructs: effect of oral ferutinin treatment in rats. Life Sci 2014; 121:174-83. [PMID: 25445219 DOI: 10.1016/j.lfs.2014.10.020] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Revised: 10/16/2014] [Accepted: 10/18/2014] [Indexed: 02/08/2023]
Abstract
AIMS This study aims to evaluate the bone regeneration in a rat calvarias critical size bone defect treated with a construct consisting of collagen type I and human amniotic fluid stem cells (AFSCs) after oral administration of phytoestrogen ferutinin. MAIN METHODS In 12 week old male rats (n=10), we performed two symmetric full-thickness cranial defects on each parietal region, and a scaffold was implanted into each cranial defect. The rats were divided into four groups: 1) collagen scaffold, 2) collagen scaffold+ferutinin at a dose of 2mg/kg/5 mL, 3) collagen scaffold + AFSCs, and 4) collagen scaffold + AFSCs + ferutinin. The rats were sacrificed after 4 weeks, and the calvariae were removed, fixed, embedded in paraffin and cut into 7 μm thick sections. Histomorphometric measures, immunohistochemical and immunofluorescence analyses were performed on the paraffin sections. KEY FINDINGS The histomorphometric analysis on H&E stained sections showed a significant increase in the regenerated area of the 4th group compared with the other groups. Immunohistochemistry performed with a human anti-mitochondrial antibody showed the presence of AFSCs 4 weeks after the transplant. Immunofluorescence analysis revealed the presence of osteocalcin and estrogen receptors (ERα and GPR30) in all groups, with a greater expression of all markers in samples where the scaffold was treated with AFSCs and the rats were orally administered ferutinin. SIGNIFICANCE Our results demonstrated that the oral administration of ferutinin is able to improve the bone regeneration of critical-size bone defects in vivo that is obtained with collagen-AFSCs constructs.
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Affiliation(s)
- Manuela Zavatti
- Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplants, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.
| | - Laura Bertoni
- Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplants, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Tullia Maraldi
- Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplants, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Elisa Resca
- Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplants, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Francesca Beretti
- Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplants, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | | | - Giovanni B La Sala
- Unit of Obstetrics & Gynecology, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy
| | - Anto De Pol
- Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplants, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
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Abstract
Segmental bone loss represents a difficult clinical entity for the treating orthopedic surgeon. This article discusses the various treatment modalities available for limb reconstruction, with a focus on the indications, potential complications, and the outcomes of available treatment options.
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Smith E, Kanczler J, Gothard D, Roberts C, Wells J, White L, Qutachi O, Sawkins M, Peto H, Rashidi H, Rojo L, Stevens M, El Haj A, Rose F, Shakesheff K, Oreffo R. Evaluation of skeletal tissue repair, part 1: assessment of novel growth-factor-releasing hydrogels in an ex vivo chick femur defect model. Acta Biomater 2014; 10:4186-96. [PMID: 24937137 DOI: 10.1016/j.actbio.2014.06.011] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2014] [Revised: 05/21/2014] [Accepted: 06/09/2014] [Indexed: 01/08/2023]
Abstract
Current clinical treatments for skeletal conditions resulting in large-scale bone loss include autograft or allograft, both of which have limited effectiveness. In seeking to address bone regeneration, several tissue engineering strategies have come to the fore, including the development of growth factor releasing technologies and appropriate animal models to evaluate repair. Ex vivo models represent a promising alternative to simple in vitro systems or complex, ethically challenging in vivo models. We have developed an ex vivo culture system of whole embryonic chick femora, adapted in this study as a critical size defect model to investigate the effects of novel bone extracellular matrix (bECM) hydrogel scaffolds containing spatio-temporal growth factor-releasing microparticles and skeletal stem cells on bone regeneration, to develop a viable alternative treatment for skeletal degeneration. Alginate/bECM hydrogels combined with poly (d,l-lactic-co-glycolic acid) (PDLLGA)/triblock copolymer (10-30% PDLLGA-PEG-PDLLGA) microparticles releasing VEGF, TGF-β3 or BMP-2 were placed, with human adult Stro-1+ bone marrow stromal cells, into 2mm central segmental defects in embryonic chick femurs. Alginate/bECM hydrogels loaded with HSA/VEGF or HSA/TGF-β3 demonstrated a cartilage-like phenotype, with minimal collagen I deposition, comparable to HSA-only control hydrogels. The addition of BMP-2 releasing microparticles resulted in enhanced structured bone matrix formation, evidenced by increased Sirius red-stained matrix and collagen expression within hydrogels. This study demonstrates delivery of bioactive growth factors from a novel alginate/bECM hydrogel to augment skeletal tissue formation and the use of an organotypic chick femur defect culture system as a high-throughput test model for scaffold/cell/growth factor therapies for regenerative medicine.
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Smith EL, Kanczler JM, Gothard D, Roberts CA, Wells JA, White LJ, Qutachi O, Sawkins MJ, Peto H, Rashidi H, Rojo L, Stevens MM, El Haj AJ, Rose FRAJ, Shakesheff KM, Oreffo ROC. Evaluation of skeletal tissue repair, part 2: enhancement of skeletal tissue repair through dual-growth-factor-releasing hydrogels within an ex vivo chick femur defect model. Acta Biomater 2014; 10:4197-205. [PMID: 24907660 DOI: 10.1016/j.actbio.2014.05.025] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2014] [Revised: 05/03/2014] [Accepted: 05/23/2014] [Indexed: 11/29/2022]
Abstract
There is an unmet need for improved, effective tissue engineering strategies to replace or repair bone damaged through disease or injury. Recent research has focused on developing biomaterial scaffolds capable of spatially and temporally releasing combinations of bioactive growth factors, rather than individual molecules, to recapitulate repair pathways present in vivo. We have developed an ex vivo embryonic chick femur critical size defect model and applied the model in the study of novel extracellular matrix (ECM) hydrogel scaffolds containing spatio-temporal combinatorial growth factor-releasing microparticles and skeletal stem cells for bone regeneration. Alginate/bovine bone ECM (bECM) hydrogels combined with poly(d,l-lactic-co-glycolic acid) (PDLLGA)/triblock copolymer (10-30% PDLLGA-PEG-PLDLGA) microparticles releasing dual combinations of vascular endothelial growth factor (VEGF), chondrogenic transforming growth factor beta 3 (TGF-β3) and the bone morphogenetic protein BMP2, with human adult Stro-1+bone marrow stromal cells (HBMSCs), were placed into 2mm central segmental defects in embryonic day 11 chick femurs and organotypically cultured. Hydrogels loaded with VEGF combinations induced host cell migration and type I collagen deposition. Combinations of TGF-β3/BMP2, particularly with Stro-1+HBMSCs, induced significant formation of structured bone matrix, evidenced by increased Sirius red-stained matrix together with collagen expression demonstrating birefringent alignment within hydrogels. This study demonstrates the successful use of the chick femur organotypic culture system as a high-throughput test model for scaffold/cell/growth factor therapies in regenerative medicine. Temporal release of dual growth factors, combined with enriched Stro-1+HBMSCs, improved the formation of a highly structured bone matrix compared to single release modalities. These studies highlight the potential of a unique alginate/bECM hydrogel dual growth factor release platform for bone repair.
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Affiliation(s)
- E L Smith
- Bone & Joint Research Group, Human Development and Health, Institute of Developmental Sciences, University of Southampton, Southampton, UK.
| | - J M Kanczler
- Bone & Joint Research Group, Human Development and Health, Institute of Developmental Sciences, University of Southampton, Southampton, UK
| | - D Gothard
- Bone & Joint Research Group, Human Development and Health, Institute of Developmental Sciences, University of Southampton, Southampton, UK
| | - C A Roberts
- Bone & Joint Research Group, Human Development and Health, Institute of Developmental Sciences, University of Southampton, Southampton, UK
| | - J A Wells
- Bone & Joint Research Group, Human Development and Health, Institute of Developmental Sciences, University of Southampton, Southampton, UK
| | - L J White
- The Wolfson Centre for Stem Cells, Tissue Engineering & Modelling (STEM), School of Pharmacy, University of Nottingham, Nottingham, UK
| | - O Qutachi
- The Wolfson Centre for Stem Cells, Tissue Engineering & Modelling (STEM), School of Pharmacy, University of Nottingham, Nottingham, UK
| | - M J Sawkins
- The Wolfson Centre for Stem Cells, Tissue Engineering & Modelling (STEM), School of Pharmacy, University of Nottingham, Nottingham, UK
| | - H Peto
- The Wolfson Centre for Stem Cells, Tissue Engineering & Modelling (STEM), School of Pharmacy, University of Nottingham, Nottingham, UK
| | - H Rashidi
- The Wolfson Centre for Stem Cells, Tissue Engineering & Modelling (STEM), School of Pharmacy, University of Nottingham, Nottingham, UK
| | - L Rojo
- Department of Materials, Imperial College London, London, UK; Institute for Biomedical Engineering, Imperial College London, London, UK; Institute of Polymer Science & Technology, CSIC and CIBER-BBN, Madrid, Spain
| | - M M Stevens
- Department of Materials, Imperial College London, London, UK; Institute for Biomedical Engineering, Imperial College London, London, UK; Department of Bioengineering, Imperial College London, London, UK
| | - A J El Haj
- Institute for Science and Technology in Medicine, School of Medicine, Keele University, Newcastle-under-Lyme, UK
| | - F R A J Rose
- The Wolfson Centre for Stem Cells, Tissue Engineering & Modelling (STEM), School of Pharmacy, University of Nottingham, Nottingham, UK
| | - K M Shakesheff
- The Wolfson Centre for Stem Cells, Tissue Engineering & Modelling (STEM), School of Pharmacy, University of Nottingham, Nottingham, UK.
| | - R O C Oreffo
- Bone & Joint Research Group, Human Development and Health, Institute of Developmental Sciences, University of Southampton, Southampton, UK.
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Nosewicz TL, Reilingh ML, Wolny M, van Dijk CN, Duda GN, Schell H. Influence of basal support and early loading on bone cartilage healing in press-fitted osteochondral autografts. Knee Surg Sports Traumatol Arthrosc 2014; 22:1445-51. [PMID: 23479055 DOI: 10.1007/s00167-013-2453-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2012] [Accepted: 02/18/2013] [Indexed: 12/15/2022]
Abstract
PURPOSE The influence of basal graft support combined to early loading following an osteochondral autograft procedure is unclear. It was hypothesized that bottomed grafts may allow for early mobilization by preventing graft subsidence and leading to better healing. METHODS Osteochondral autografts were press fitted in the femoral condyles of 24 sheep (one graft per animal). In the unbottomed group (n = 12), a gap of 2 mm was created between graft and recipient bone base. In the bottomed group (n = 12), the graft firmly rested on recipient bone. Animals were allowed immediate postoperative weightbearing. Healing times were 3 and 6 months per group (n = 6 per subgroup). After killing, histological and histomorphometric analyses were performed. RESULTS Unbottomed grafts at 3 months showed significantly more graft subsidence (P = 0.024), significantly less mineralized bone (P = 0.028) and significantly worse cartilage and subchondral bone plate healing (P = 0.034) when compared to bottomed grafts. At 6 months, no differences were seen. Compared to the native situation, unbottomed grafts showed significantly more graft subsidence (P = 0.024), whereas bottomed grafts did not. Cystic lesions were seen in both groups. Osteoclasts were closely related to the degree of bone remodelling. CONCLUSION In the animal model, in the case of early loading, bottomed osteochondral autografts have less chance of graft subsidence. Evident subsidence negatively influences the histological healing process. In the osteochondral autograft procedure, full graft support should be aimed for. This may allow for early mobilization, diminish graft subsidence and improve long-term integration.
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Affiliation(s)
- Tomasz L Nosewicz
- Julius Wolff Institute and Center for Musculoskeletal Surgery and Berlin-Brandenburg Center for Regenerative Therapies, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, Forum 4, Postbox 24, 13353, Berlin, Germany,
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Oryan A, Bigham-Sadegh A, Abbasi-Teshnizi F. Effects of osteogenic medium on healing of the experimental critical bone defect in a rabbit model. Bone 2014; 63:53-60. [PMID: 24582803 DOI: 10.1016/j.bone.2014.02.010] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2013] [Revised: 02/13/2014] [Accepted: 02/18/2014] [Indexed: 10/25/2022]
Abstract
Today, finding an ideal biomaterial to treat the large bone defects, delayed unions and non-unions remains a challenge for orthopedic surgeons and researchers. Several studies have been carried out on the subject of bone regeneration, each having its own advantages. At the same time, a variety of disadvantages still remain. The present study has been designed in vivo to evaluate the effects of osteogenic medium on healing of experimental critical bone defect in a rabbit model. Twenty New Zealand albino rabbits, 12 months old, of both sexes, weighing 2.0±0.5 kg were used in this study. An approximately 10mm segmental defect was created in the mid portion of each radius as a critical size bone defect. In the osteogenic medium group (n=5) 1 ml osteogenic medium, in the maintenance medium group (n=5) 1 ml maintenance medium, and in the normal saline group (n=5) 1 ml normal saline were injected in the defected area while the defects of the rabbits of the control group (n=5) were left empty. Radiological evaluation was done on the 1st day and then at the 2nd, 4th, 6th and 8th weeks post injury. Biomechanical and histopathological evaluations were done 8 weeks post injury. The radiological, histological and biomechanical findings of the present study indicated a superior bone healing capability in the osteogenic and maintenance medium groups, by the end of 8 weeks post-surgery, in comparison to the normal saline and control groups. In conclusion, this study demonstrated that the osteogenic medium and maintenance medium could promote bone regeneration in long bone defects better than the control group in rabbit model.
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Affiliation(s)
- Ahmad Oryan
- Department of Veterinary Pathology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | | | - Fatemeh Abbasi-Teshnizi
- Department of Veterinary Pathology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
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Liu J, Mao K, Liu Z, Wang X, Cui F, Guo W, Mao K, Yang S. Injectable biocomposites for bone healing in rabbit femoral condyle defects. PLoS One 2013; 8:e75668. [PMID: 24146770 PMCID: PMC3797737 DOI: 10.1371/journal.pone.0075668] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2013] [Accepted: 08/16/2013] [Indexed: 11/23/2022] Open
Abstract
A novel biomimetic bone scaffold was successfully prepared in this study, which was composed of calcium sulfate hemihydrate (CSH), collagen and nano-hydroxyapatite (nHAC). CSH/nHAC was prepared and observed with scanning electron microscope and rhBMP-2 was introduced into CSH/nHAC. The released protein content from the scaffold was detected using high performance liquid chromatography at predetermined time interval. In vivo bone formation capacity was investigated by means of implanting the scaffolds with rhBMP-2 or without rhBMP-2 respectively into a critical size defect model in the femoral condyle of rabbit. The releasing character of rhBMP-2 was that an initial burst release (37.5%) was observed in the first day, followed by a sustained release and reached 100% at the end of day 20. The CSH/nHAC showed a gradual decrease in degradation with the content of nHAC increase. The results of X-rays, Micro CT and histological observation indicated that more new bone was formed in rhBMP-2 group. The results implied that this new injectable bone scaffold should be very promising for bone repair and has a great potential in bone tissue engineering.
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Affiliation(s)
- Jianheng Liu
- Department of Orthopaedics, General Hospital of People's Liberation Army, Beijing, China
| | - Kezheng Mao
- Department of Orthopaedics, General Hospital of People's Liberation Army, Beijing, China
| | - Zhengsheng Liu
- Department of Orthopaedics, General Hospital of People's Liberation Army, Beijing, China
| | - Xiumei Wang
- Department of Materials Science and Engineering, Tsinghua University, Beijing, China
| | - Fuzhai Cui
- Department of Materials Science and Engineering, Tsinghua University, Beijing, China
| | - Wenguang Guo
- Beijing Olympic fine Pharmaceutical Technology Co., Ltd, Beijing, China
| | - Keya Mao
- Department of Orthopaedics, General Hospital of People's Liberation Army, Beijing, China
- * E-mail: (KM); (SY)
| | - Shuying Yang
- Department of Oral Biology, University at Buffalo - SUNY, Buffalo, New York, United States of America
- * E-mail: (KM); (SY)
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Zhang X, Liu T, Huang Y, Wismeijer D, Liu Y. Icariin: Does It Have An Osteoinductive Potential for Bone Tissue Engineering? Phytother Res 2013; 28:498-509. [DOI: 10.1002/ptr.5027] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2013] [Revised: 04/07/2013] [Accepted: 05/21/2013] [Indexed: 01/23/2023]
Affiliation(s)
- Xin Zhang
- School of Stomatology; Tongji University; Shanghai China
| | - Tie Liu
- Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE; University of Amsterdam and VU University Amsterdam; Gustav Mahlerlaan 3004 1081 LA Amsterdam the Netherlands
| | - Yuanliang Huang
- Department of Dentistry; Shanghai East Hospital Affiliated to Tongji University; Shanghai China
| | - Daniel Wismeijer
- Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE; University of Amsterdam and VU University Amsterdam; Gustav Mahlerlaan 3004 1081 LA Amsterdam the Netherlands
| | - Yuelian Liu
- Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE; University of Amsterdam and VU University Amsterdam; Gustav Mahlerlaan 3004 1081 LA Amsterdam the Netherlands
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Supronowicz P, Gill E, Trujillo A, Thula T, Zhukauskas R, Perry R, Cobb RR. Multipotent adult progenitor cell-loaded demineralized bone matrix for bone tissue engineering. J Tissue Eng Regen Med 2013; 10:275-83. [PMID: 23413005 DOI: 10.1002/term.1706] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2010] [Revised: 11/28/2012] [Accepted: 12/20/2012] [Indexed: 11/10/2022]
Abstract
Multipotent adult progenitor cells (MAPCs) from bone marrow have been shown to be capable of forming bone, cartilage and other connective tissues. In addition, MAPCs differentiate into lineages that are different from their germ layers of origin. Previous studies showed the ability of MAPCs to improve cardiac function and control allogenic-reactive responses associated with acute graft versus host disease. In the current study, we evaluated the ability of MAPCs to produce bone matrix on demineralized bone allograft substrates. Specifically, MAPCs expressed alkaline phosphatase, produced extracellular matrix proteins and deposited calcium-containing mineral on demineralized bone matrices. Furthermore, the addition of MAPCs on demineralized bone matrix (DBM) scaffolds enhanced osteoinductivity of the carrier in a rat ectopic pouch model. These results demonstrated the potential of MAPCs as a new approach for bone repair in tissue-engineering applications.
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Affiliation(s)
- Peter Supronowicz
- Biotechnology Development Department, RTI Biologics, Alachua, FL, USA
| | - Elise Gill
- Biotechnology Development Department, RTI Biologics, Alachua, FL, USA
| | - Angelica Trujillo
- Biotechnology Development Department, RTI Biologics, Alachua, FL, USA
| | - Taili Thula
- Biotechnology Development Department, RTI Biologics, Alachua, FL, USA
| | | | | | - Ronald R Cobb
- Biotechnology Development Department, RTI Biologics, Alachua, FL, USA
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Soucacos PN, Kokkalis ZT, Piagkou M, Johnson EO. Vascularized bone grafts for the management of skeletal defects in orthopaedic trauma and reconstructive surgery. Injury 2013; 44 Suppl 1:S70-5. [PMID: 23351876 DOI: 10.1016/s0020-1383(13)70016-0] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Bone loss from trauma, neoplasia, reconstructive surgery and congenital defects remains a major health problem. The long-term clinical goal is to reconstruct bony tissue in an anatomically functional three-dimensional morphology. In the extremities, bone grafts are used for the treatment of non-unions and necrotic lesions, for skeletal structural support and for the reconstruction of defects resulting from trauma, tumor excision, osteomyelitis, congenital pseudarthrosis, or radiation necrosis. In all cases their use is successful provided that the host bed has adequate vascularization. In cases of decreased blood supply, a vascularized bone graft should be applied. The intrinsic blood supply of the vascularized bone grafts leads to higher success rates and to acceleration of the repair process in the reconstruction of defects and necrotic lesions of the skeleton.
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Affiliation(s)
- Panayotis N Soucacos
- Orthopaedic Research and Education Center (OREC), Attikon University Hospital, University of Athens, School of Medicine, Athens, Greece.
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Reichert JC, Berner A, Saifzadeh S, Hutmacher DW. Preclinical Animal Models for Segmental Bone Defect Research and Tissue Engineering. Regen Med 2013. [DOI: 10.1007/978-94-007-5690-8_40] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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Ferretti C, Borsari V, Falconi M, Gigante A, Lazzarini R, Fini M, Di Primio R, Mattioli-Belmonte M. Human periosteum-derived stem cells for tissue engineering applications: the role of VEGF. Stem Cell Rev Rep 2012; 8:882-90. [PMID: 22622690 DOI: 10.1007/s12015-012-9374-7] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Mesenchymal stem cells (MSCs) are promising tools for studying the mechanisms of development and for the regeneration of injured tissues. Correct selection of the MSCs source is crucial in order to obtain a more efficient treatment and, in this respect Periosteum-Derived Cells (PDPCs) may represent an interesting alternative to bone marrow MSCs for osteochondral tissue regeneration. In the present study we have isolated and characterized a MSCs population from the periosteum of human adult donors. PDPCs were expanded under specific culture conditions that prevent fibroblast contamination and support the maintenance of their undifferentiated phenotype. We show, for the first time, that PDPCs expresses VEGF receptor (Flt1 and KDR/Flk1) proteins and that they were similar to bone marrow Multipotent Adult Progenitor Cells (MAPCs). Since the latter are able to differentiate into endothelial cells, we tested the possible PDPCs commitment toward an endothelial phenotype in view of bone tissue engineering approaches that takes into account not only bone formation but also vascularization. PDPCs were treated with two different VEGF concentrations for 7 and 15 days and, alternatively, with the supernatant of human primary osteoblasts. Differently from MAPCs our PDPCs were unable to differentiate into endothelial cells after their in vitro VEGF treatment. On the contrary, growth factor stimulation induces PDPCs differentiation toward osteoblasts. We concluded that in PDPCs the presence of VEGF receptors is related to different cross-talk between osteogenesis and angiogenesis that could involve in situ PDPCs recruitment.
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Affiliation(s)
- C Ferretti
- Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Via Tonto 10/a, 60126 Ancona, Italy
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Glatt V, Miller M, Ivkovic A, Liu F, Parry N, Griffin D, Vrahas M, Evans C. Improved healing of large segmental defects in the rat femur by reverse dynamization in the presence of bone morphogenetic protein-2. J Bone Joint Surg Am 2012; 94:2063-73. [PMID: 23172324 PMCID: PMC3497904 DOI: 10.2106/jbjs.k.01604] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Large segmental defects in bone do not heal well and present clinical challenges. This study investigated modulation of the mechanical environment as a means of improving bone healing in the presence of bone morphogenetic protein (BMP)-2. Although the influence of mechanical forces on the healing of fractures is well established, no previous studies, to our knowledge, have described their influence on the healing of large segmental defects. We hypothesized that bone-healing would be improved by initial, low-stiffness fixation of the defect, followed by high-stiffness fixation during the healing process. We call this reverse dynamization. METHODS A rat model of a critical-sized femoral defect was used. External fixators were constructed to provide different degrees of stiffness and, importantly, the ability to change stiffness during the healing process in vivo. Healing of the critical-sized defects was initiated by the implantation of 11 μg of recombinant human BMP (rhBMP)-2 on a collagen sponge. Groups of rats receiving BMP-2 were allowed to heal with low, medium, and high-stiffness fixators, as well as under conditions of reverse dynamization, in which the stiffness was changed from low to high at two weeks. Healing was assessed at eight weeks with use of radiographs, histological analysis, microcomputed tomography, dual x-ray absorptiometry, and mechanical testing. RESULTS Under constant stiffness, the low-stiffness fixator produced the best healing after eight weeks. However, reverse dynamization provided considerable improvement, resulting in a marked acceleration of the healing process by all of the criteria of this study. The histological data suggest that this was the result of intramembranous, rather than endochondral, ossification. CONCLUSIONS Reverse dynamization accelerated healing in the presence of BMP-2 in the rat femur and is worthy of further investigation as a means of improving the healing of large segmental bone defects. CLINICAL RELEVANCE These data provide the basis of a novel, simple, and inexpensive way to improve the healing of critical-sized defects in long bones. Reverse dynamization may also be applicable to other circumstances in which bone-healing is problematic.
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Affiliation(s)
- Vaida Glatt
- Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, 330, Brookline Avenue, RN-115, Boston, MA 02215. E-mail address for V. Glatt:
| | - Micah Miller
- Harvard Orthopaedic Trauma Service, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114
| | - Alan Ivkovic
- Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, 330, Brookline Avenue, RN-115, Boston, MA 02215. E-mail address for V. Glatt:
| | - Fangjun Liu
- Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, 330, Brookline Avenue, RN-115, Boston, MA 02215. E-mail address for V. Glatt:
| | - Nicola Parry
- Division of Comparative Medicine, Massachusetts Institute of Technology, Building 16, Room 825, 77 Massachusetts Avenue, Cambridge, MA 02139
| | - Damian Griffin
- Department of Orthopaedic Surgery, Warwick University Medical School, Coventry CV4 7AL, United Kingdom
| | - Mark Vrahas
- Harvard Orthopaedic Trauma Service, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114
| | - Christopher Evans
- Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, 330, Brookline Avenue, RN-115, Boston, MA 02215. E-mail address for V. Glatt:
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Bielecki T, Cieslik-Bielecka A, Żelawski M, Mikusek W. A side-effect induced by the combination of a demineralized freeze-dried bone allograft and leucocyte and platelet-rich plasma during treatment for large bone cysts: A 4-year follow-up clinical study. Transfus Apher Sci 2012; 47:133-8. [DOI: 10.1016/j.transci.2012.06.017] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2012] [Revised: 05/23/2012] [Accepted: 06/29/2012] [Indexed: 01/21/2023]
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Rapp SJ, Jones DC, Gerety P, Taylor JA. Repairing critical-sized rat calvarial defects with progenitor cell-seeded acellular periosteum: A novel biomimetic scaffold. Surgery 2012; 152:595-604, 605.e1; discussion 604-5. [DOI: 10.1016/j.surg.2012.07.019] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2012] [Accepted: 07/12/2012] [Indexed: 01/22/2023]
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