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Li Y, Ge Z, Liu Z, Li L, Song J, Wang H, Tian F, Lei P, Li L, Xue J. Integrating electrospun aligned fiber scaffolds with bovine serum albumin-basic fibroblast growth factor nanoparticles to promote tendon regeneration. J Nanobiotechnology 2024; 22:799. [PMID: 39731092 DOI: 10.1186/s12951-024-03022-1] [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: 04/12/2024] [Accepted: 11/14/2024] [Indexed: 12/29/2024] Open
Abstract
BACKGROUND Electrospun nanofiber scaffolds have been widely used in tissue engineering because they can mimic extracellular matrix-like structures and offer advantages including high porosity, large specific surface area, and customizable structure. In this study, we prepared scaffolds composed of aligned and random electrospun polycaprolactone (PCL) nanofibers capable of delivering basic fibroblast growth factor (bFGF) in a sustained manner for repairing damaged tendons. RESULTS Aligned and random PCL fiber scaffolds containing bFGF-loaded bovine serum albumin (BSA) nanoparticles (BSA-bFGF NPs, diameter 146 ± 32 nm) were fabricated, respectively. To validate the viability of bFGF-loaded aligned PCL nanofiber scaffold (aPCL + bFGF group) in tendon tissue engineering, we assessed the in vitro differentiation of human amniotic mesenchymal stem cells (hAMSCs) towards a tenogenic lineage and the in vivo regeneration of tendons using a rat Achilles tendon defect model. The encapsulated bFGF could be delivered in a sustained manner in vitro. The aPCL + bFGF scaffold promoted the in vitro differentiation of human amniotic mesenchymal stem cells (hAMSCs) towards a tenogenic lineage. In the repair of a rat Achilles tendon defect model, the aPCL + bFGF group showed a better repair effect. The scaffold offers a promising substrate for the regeneration of tendon tissue. CONCLUSIONS The aligned and random PCL fiber scaffolds containing bFGF nanoparticles were successfully prepared, and their physical and chemical properties were characterized. The aPCL + bFGF scaffold could promote the expression of the related genes and proteins of tendon-forming, facilitating tendon differentiation. In the rat Achilles tendon defect experiments, the aPCL + bFGF exhibited excellent tendon regeneration effects.
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Affiliation(s)
- Yuwan Li
- Department of Orthopaedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China
| | - Zhen Ge
- Department of Orthopaedics, Haining People's Hospital, Haining, 314400, Zhejiang, China
- Department of Orthopaedics, the First Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Ziming Liu
- Beijing Key Laboratory of Sports Injuries, Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing, 100191, China
| | - Longfei Li
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China
| | - Jian Song
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China
| | - Hongde Wang
- Beijing Key Laboratory of Sports Injuries, Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing, 100191, China
| | - Feng Tian
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China
| | - Pengfei Lei
- Department of Orthopaedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China.
| | - Long Li
- College of Materials and Metallurgy, Guizhou University, Guiyang, 550025, Guizhou, China.
| | - Jiajia Xue
- State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China.
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Zhang X, Wu Y, Han K, Fang Z, Cho E, Hu Y, Huangfu X, Zhao J. 3-Dimensional Bioprinting of a Tendon Stem Cell-Derived Exosomes Loaded Scaffold to Bridge the Unrepairable Massive Rotator Cuff Tear. Am J Sports Med 2024; 52:2358-2371. [PMID: 38904220 DOI: 10.1177/03635465241255918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/22/2024]
Abstract
BACKGROUND Unrepairable massive rotator cuff tears (UMRCTs) are challenging to surgeons owing to the severely retracted rotator cuff musculotendinous tissues and extreme defects in the rotator cuff tendinous tissues. PURPOSE To fabricate a tendon stem cell-derived exosomes loaded scaffold (TSC-Exos-S) and investigate its effects on cellular bioactivity in vitro and repair in a rabbit UMRCT model in vivo. STUDY DESIGN Controlled laboratory study. METHODS TSC-Exos-S was fabricated by loading TSC-Exos and type 1 collagen (COL-I) into a 3-dimensional bioprinted and polycaprolactone (PCL)-based scaffold. The proliferation, migration, and tenogenic differentiation activities of rabbit bone marrow stem cells (BMSCs) were evaluated in vitro by culturing them in saline, PCL-based scaffold (S), COL-I loaded scaffold (COL-I-S), and TSC-Exos-S. In vivo studies were conducted on a rabbit UMRCT model, where bridging was repaired with S, COL-I-S, TSC-Exos-S, and autologous fascia lata (FL). Histological and biomechanical analyses were performed at 8 and 16 weeks postoperatively. RESULTS TSC-Exos-S exhibited reliable mechanical strength and subcutaneous degradation, which did not occur before tissue regeneration. TSC-Exos-S significantly promoted the proliferation, migration, and tenogenic differentiation of rabbit BMSCs in vitro. In vivo studies showed that UMRCT repaired with TSC-Exos-S exhibited significant signs of tendinous tissue regeneration at the bridging site with regard to specific collagen staining. Moreover, no significant differences were observed in the histological and biomechanical properties compared with those repaired with autologous FL. CONCLUSION TSC-Exos-S achieved tendinous tissue regeneration in UMRCT by providing mechanical support and promoting the trend toward tenogenic differentiation. CLINICAL RELEVANCE The present study proposes a potential strategy for repairing UMRCT with severely retracted musculotendinous tissues and large tendinous tissue defects.
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Affiliation(s)
- Xuancheng Zhang
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuxu Wu
- Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Kang Han
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhaoyi Fang
- Biodynamics Laboratory, Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Eunshinae Cho
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yihe Hu
- Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaoqiao Huangfu
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jinzhong Zhao
- Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Yeo YH, Jo SK, Kim MH, Lee SJ, Han SY, Park MH, Kim DY, Kim DY, Yoo IH, Kang C, Song JH, Park WH. Fabrication of atelocollagen-coated bioabsorbable suture and the evaluation of its regenerative efficacy in Achilles tendon healing using a rat experimental model. Int J Biol Macromol 2024; 271:132564. [PMID: 38782324 DOI: 10.1016/j.ijbiomac.2024.132564] [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: 04/16/2024] [Revised: 05/18/2024] [Accepted: 05/20/2024] [Indexed: 05/25/2024]
Abstract
Recently, the incidence of Achilles tendon ruptures (ATRs) has become more common, and repair surgery using a bioabsorbable suture is generally preferred, particularly in the case of healthy patients. Sutures composed of poly(lactic-co-glycolic acid) (PLGA) are commonly used in ATR surgeries. Nevertheless, owing to the inherent limitations of PLGA, novel bioabsorbable sutures that can accelerate Achilles tendon healing are sought. Recently, several studies have demonstrated the beneficial effects of atelocollagen on tendon healing. In this study, poly(3,4-dihydroxy-L-phenylalanine) (pDOPA), a hydrophilic biomimetic material, was used to modify the hydrophobic surface of a PLGA suture (Vicryl, VC) for the stable coating of atelocollagen on its surface. The main objective was to fabricate an atelocollagen-coated VC suture and evaluate its performance in the healing of Achilles tendon using a rat model of open repair for ATR. Structural analyses of the surface-modified suture indicated that the collagen was successfully coated on the VC/pDOPA suture. Postoperative in vivo biomechanical analysis, histological evaluation, ultrastructural/morphological analyses, and western blotting confirmed that the tendons in the VC/pDOPA/Col group exhibit superior healing than those in the VC and VC/pDOPA groups after 1 and 6 weeks following the surgery. The this study suggests that atelocollagen-coated PLGA/pDOPA sutures are preferable for future medical applications, especially in the repair of ATR.
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Affiliation(s)
- Yong Ho Yeo
- Department of Organic Materials Engineering, Chungnam National University, Daejeon, Republic of Korea
| | - Seong Kyeong Jo
- Department of Orthopedic Surgery, Konyang University Hospital, Daejeon, Republic of Korea
| | - Min Hee Kim
- Department of Textile Engineering, Kyungpook National University, Republic of Korea
| | - Su Jeong Lee
- R&D planning team, Organoid Sciences Co., Ltd., 331, Pangyo-ro, Bundang-gu, Seongnam-si, Republic of Korea
| | - Seung Yun Han
- Department of Anatomy, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Mun Hyang Park
- Department of Pathology, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Dae Young Kim
- Department of Pathology, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Dae Yeung Kim
- Department of Orthopedic Surgery, Konyang University Hospital, Daejeon, Republic of Korea
| | - In Ha Yoo
- Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Chan Kang
- Department of Orthopedic Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - Jae Hwang Song
- Department of Orthopedic Surgery, Konyang University Hospital, Daejeon, Republic of Korea.
| | - Won Ho Park
- Department of Organic Materials Engineering, Chungnam National University, Daejeon, Republic of Korea.
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Taguchi T, Lopez M, Takawira C. Viable tendon neotissue from adult adipose-derived multipotent stromal cells. Front Bioeng Biotechnol 2024; 11:1290693. [PMID: 38260742 PMCID: PMC10800559 DOI: 10.3389/fbioe.2023.1290693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 12/11/2023] [Indexed: 01/24/2024] Open
Abstract
Background: Tendon healing is frequently prolonged, unpredictable, and results in poor tissue quality. Neotissue formed by adult multipotent stromal cells has the potential to guide healthy tendon tissue formation. Objectives: The objective of this study was to characterize tendon neotissue generated by equine adult adipose-derived multipotent stromal cells (ASCs) on collagen type I (COLI) templates under 10% strain in a novel bioreactor. The tested hypothesis was that ASCs assume a tendon progenitor cell-like morphology, express tendon-related genes, and produce more organized extracellular matrix (ECM) in tenogenic versus stromal medium with perfusion and centrifugal fluid motion. Methods: Equine ASCs on COLI sponge cylinders were cultured in stromal or tenogenic medium within bioreactors during combined perfusion and centrifugal fluid motion for 7, 14, or 21 days under 10% strain. Viable cell distribution and number, tendon-related gene expression, and micro- and ultra-structure were evaluated with calcein-AM/EthD-1 staining, resazurin reduction, RT-PCR, and light, transmission, and scanning electron microscopy. Fibromodulin was localized with immunohistochemistry. Cell number and gene expression were compared between culture media and among culture periods (p < 0.05). Results: Viable cells were distributed throughout constructs for up to 21 days of culture, and cell numbers were higher in tenogenic medium. Individual cells had a round or rhomboid shape with scant ECM in stromal medium in contrast to clusters of parallel, elongated cells surrounded by highly organized ECM in tenogenic medium after 21 days of culture. Transcription factor, extracellular matrix, and mature tendon gene expression profiles confirmed ASC differentiation to a tendon progenitor-like cell in tenogenic medium. Construct micro- and ultra-structure were consistent with tendon neotissue and fibromodulin was present in the ECM after culture in tenogenic medium. Conclusion: Long-term culture in custom bioreactors with combined perfusion and centrifugal tenogenic medium circulation supports differentiation of equine adult ASCs into tendon progenitor-like cells capable of neotissue formation.
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Yu YH, Lee CH, Hsu YH, Chou YC, Yu PC, Huang CT, Liu SJ. Anti-Adhesive Resorbable Indomethacin/Bupivacaine-Eluting Nanofibers for Tendon Rupture Repair: In Vitro and In Vivo Studies. Int J Mol Sci 2023; 24:16235. [PMID: 38003425 PMCID: PMC10671766 DOI: 10.3390/ijms242216235] [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: 10/20/2023] [Revised: 11/08/2023] [Accepted: 11/09/2023] [Indexed: 11/26/2023] Open
Abstract
The treatment and surgical repair of torn Achilles tendons seldom return the wounded tendon to its original elasticity and stiffness. This study explored the in vitro and in vivo simultaneous release of indomethacin and bupivacaine from electrospun polylactide-polyglycolide composite membranes for their capacity to repair torn Achilles tendons. These membranes were fabricated by mixing polylactide-polyglycolide/indomethacin, polylactide-polyglycolide/collagen, and polylactide-polyglycolide/bupivacaine with 1,1,1,3,3,3-hexafluoro-2-propanol into sandwich-structured composites. Subsequently, the in vitro pharmaceutic release rates over 30 days were determined, and the in vivo release behavior and effectiveness of the loaded drugs were assessed using an animal surgical model. High concentrations of indomethacin and bupivacaine were released for over four weeks. The released pharmaceutics resulted in complete recovery of rat tendons, and the nanofibrous composite membranes exhibited exceptional mechanical strength. Additionally, the anti-adhesion capacity of the developed membrane was confirmed. Using the electrospinning technique developed in this study, we plan on manufacturing degradable composite membranes for tendon healing, which can deliver sustained pharmaceutical release and provide a collagenous habitat.
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Affiliation(s)
- Yi-Hsun Yu
- Department of Orthopedic Surgery, Bone and Joint Research Center, Chang Gung Memorial Hospital-Linkou, Taoyuan 33305, Taiwan; (Y.-H.Y.)
| | - Chen-Hung Lee
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan
| | - Yung-Heng Hsu
- Department of Orthopedic Surgery, Bone and Joint Research Center, Chang Gung Memorial Hospital-Linkou, Taoyuan 33305, Taiwan; (Y.-H.Y.)
| | - Ying-Chao Chou
- Department of Orthopedic Surgery, Bone and Joint Research Center, Chang Gung Memorial Hospital-Linkou, Taoyuan 33305, Taiwan; (Y.-H.Y.)
| | - Ping-Chun Yu
- Department of Mechanical Engineering, Chang Gung University, Taoyuan 33302, Taiwan
| | - Chao-Tsai Huang
- Department of Chemical and Materials Engineering, Tamkang University, New Taipei City 25137, Taiwan;
| | - Shih-Jung Liu
- Department of Orthopedic Surgery, Bone and Joint Research Center, Chang Gung Memorial Hospital-Linkou, Taoyuan 33305, Taiwan; (Y.-H.Y.)
- Department of Mechanical Engineering, Chang Gung University, Taoyuan 33302, Taiwan
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Gultekin O, Kilinc BE, Akpolat AO, Cumbul A, Yilmaz B. Investigation of the effects of subacromial bursal tissue preservation and microfracture procedure on healing after rotator cuff repair in a rat model. Orthop Traumatol Surg Res 2023; 109:103608. [PMID: 36958622 DOI: 10.1016/j.otsr.2023.103608] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 02/27/2023] [Accepted: 03/16/2023] [Indexed: 03/25/2023]
Abstract
INTRODUCTION The aim of this study is to compare the preservation of bursal tissue and microfracture techniques and to examine the effectiveness of the combination of the two methods in rotator cuff tear healing in the rat shoulder. HYPOTHESIS Bursal tissue preservation combined with microfracture is more effective in the rotator cuff repair. MATERIALS AND METHODS Twenty-three male Sprague-Dawley rats were randomly divided into two groups. The bursal tissue was preserved in group 1 (n=11) and excised in group 2 (n=12). Groups were categorized into subgroups as L (left) and R (right) based on the shoulder side receiving microfracture (L received microfracture, R did not). Histopathological examination was performed using modified Bonar Score System. RESULTS Cell morphology grades of group 1 were lower than group 2 (p<0.05). In terms of collagen measurements, the grade of group 1L (bursa preservation+microfracture) was lower than groups 1R, 2L, and 2R, and the grade of group 1R was lower than groups 2L and 2R. Cellularity grades of group 2 were higher than group 1 (p<0.05). Extracellular matrix grades of group 1 were lower than group 2 (p<0.05). The overall grades were lower in group 1 than in group 2 (p<0.05). DISCUSSION Combined treatment of bursal tissue preservation and microfracture was the most efficient method as determined by healing findings in histopathological specimens. Preservation of bursal tissue was a more effective option in tendon healing than performing only microfracture. LEVEL OF PROOF II, animal research.
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Affiliation(s)
- Onur Gultekin
- Department of Orthopedics and Traumatology, Health Sciences University Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey
| | - Bekir Eray Kilinc
- Department of Orthopedics and Traumatology, Health Sciences University Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey.
| | - Ahmet Onur Akpolat
- Department of Orthopedics and Traumatology, Health Sciences University Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey
| | - Alev Cumbul
- Department of Histology, Yeditepe University, Istanbul, Turkey
| | - Baris Yilmaz
- Department of Orthopedics and Traumatology, Health Sciences University Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey
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Jo SK, Yoo IH, Park HY, Kang C, Han SY, Moon JH, Park WH, Yeo YH, Jun S, Yi YS, Lee SJ, Tae JY, Song JH. An Atelocollagen Injection Enhances the Healing of Nonoperatively Treated Achilles Tendon Tears: An Experimental Study in Rats. Orthop J Sports Med 2023; 11:23259671231200933. [PMID: 37868218 PMCID: PMC10586006 DOI: 10.1177/23259671231200933] [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: 05/10/2023] [Accepted: 05/19/2023] [Indexed: 10/24/2023] Open
Abstract
Background There is growing interest in nonoperative treatment for the management of Achilles tendon ruptures (ATRs). However, nonoperative treatment is limited by the risk of tendon reruptures and low satisfaction rates. Recently, atelocollagen injections have been reported to have beneficial effects on tendon healing. Purpose To evaluate the beneficial effects of injected atelocollagen on Achilles tendon healing and investigate the mechanism of atelocollagen on tendon healing. Study Design Controlled laboratory study. Methods Percutaneous tenotomy of the right Achilles tendon in 66 rats was performed. The animals were equally divided into the noninjection group (NG) and the collagen injection group (CG). At 1, 3, and 6 weeks, the Achilles functional index, cross-sectional area, load to failure, stiffness, stress, and the modified Bonar score were assessed. Transmission electron microscopy, western blotting, and immunohistochemistry were also performed. Results The Achilles functional index (-6.8 vs -43.0, respectively; P = .040), load to failure (42.1 vs 27.0 N, respectively; P = .049), and stiffness (18.8 vs 10.3 N/mm, respectively; P = .049) were higher in the CG than those in the NG at 3 weeks. There were no significant differences in histological scores between the 2 groups. Transmission electron microscopy analysis showed that the mean diameter of collagen fibrils in the CG was greater than that in the NG at 3 weeks (117.2 vs 72.6 nm, respectively; P < .001) and 6 weeks (202.1 vs 144.0 nm, respectively; P < .001). Western blot analysis showed that the expression of collagen type I in the CG was higher than that in the NG at 1 week (P = .005) and 6 weeks (P = .001). Conclusion An atelocollagen injection had beneficial effects on the healing of nonoperatively treated Achilles tendon injuries. The Achilles tendon of CG rats exhibited better functional, biomechanical, and morphological outcomes compared with NG rats. The molecular data indicated that the mechanism of atelocollagen injections may be associated with an increased amount of collagen type I. Clinical Relevance An atelocollagen injection might be a good adjuvant option for the nonoperative treatment of ATRs.
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Affiliation(s)
- Seong Kyeong Jo
- Department of Orthopedic Surgery, Konyang University Hospital, Daejeon, Republic of Korea
| | - In Ha Yoo
- Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyeon Yeong Park
- Department of Occupational Therapy, College of Medical Science, Konyang University, Daejeon, Republic of Korea
| | - Chan Kang
- Department of Orthopedic Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - Seung Yun Han
- Department of Anatomy, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Ji Hyun Moon
- Department of Anatomy, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Won Ho Park
- Department of Organic Materials Engineering, Chungnam National University, Daejeon, Republic of Korea
| | - Yong Ho Yeo
- Department of Organic Materials Engineering, Chungnam National University, Daejeon, Republic of Korea
| | - Sangmi Jun
- Center for Research Equipment, Korea Basic Science Institute, Daejeon, Republic of Korea
| | - Yoon-Sun Yi
- Center for Research Equipment, Korea Basic Science Institute, Daejeon, Republic of Korea
| | - Su Jeong Lee
- Department of Microbiology, School of Medicine, CHA University, Seongnam, Republic of Korea
| | - Jung Yeon Tae
- Department of Medicine, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Jae Hwang Song
- Department of Orthopedic Surgery, Konyang University Hospital, Daejeon, Republic of Korea
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Ke X, Zhang W. Pro-inflammatory activity of long noncoding RNA FOXD2-AS1 in Achilles tendinopathy. J Orthop Surg Res 2023; 18:361. [PMID: 37194076 DOI: 10.1186/s13018-023-03681-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 03/05/2023] [Indexed: 05/18/2023] Open
Abstract
Achilles tendinopathy is a prevalent clinical problem that plagues athletes and general populations. Achilles tendon healing is a complex process, and so far, there is no successful long-term solution to Achilles tendinopathy in the field of microsurgery due to its poor natural regeneration ability. Limitations in understanding the pathogenesis of Achilles tendon development and Achilles tendon injury hinder clinical treatment developments. There is an increasing demand for innovative conservative treatments that can improve Achilles tendon injury. In this study, a Sprague-Dawley rat model of Achilles tendinopathy was established. Lentiviral vectors that interfere with the expression of FOXD2-AS1, miR-21-3p, or PTEN were injected every 3 days. Rats were euthanized after 3 weeks, and the effect of FOXD2-AS1, miR-21-3p, or PTEN on Achilles tendon healing was analyzed by histological observation, biomechanical test, and examinations of inflammatory factors and tendon markers. As measured, downregulating FOXD2-AS1 or upregulating miR-21-3p improved histological structure, suppressed inflammation, promoted the expression of tendon markers, and optimized the biomechanical properties of Achilles tendon. Upregulating PTEN was capable of reversing the promoting effect of inhibition of FOXD2-AS1 on Achilles tendon healing. As concluded, deficiency of FOXD2-AS1 accelerates the healing of Achilles tendon injury and improves tendon degeneration by regulating the miR-21-3p/PTEN axis and promoting the activation of the PI3K/AKT signaling pathway.
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Affiliation(s)
- Xiaoting Ke
- Zhejiang Rehabilitation Medical Center, Hangzhou, 310051, Zhejiang, China
| | - Wenjie Zhang
- Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, 310014, Zhejiang, China.
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Altun S, Sahin MS, Çakmak G, Gokkus K, Terzi A. Effects of Routine Antithrombotic-Adjusted Dose of Rivaroxaban and Nadroparin Calcium on Tendon Healing of Rats: An Experimental Study. J Hand Microsurg 2023; 15:133-140. [PMID: 37020612 PMCID: PMC10070002 DOI: 10.1055/s-0041-1729468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
Introduction Achilles tendon injury necessitates thromboembolism prophylaxis after repair. This study aimed to investigate the effects of antithrombotic-adjusted prophylactic doses of nadroparin calcium and rivaroxaban on Achilles tendon healing. Materials and Methods Twenty-four young adult male Wistar Albino type rats were randomly divided into three groups. All rats underwent a full-thickness surgical incision of the Achilles tendon, followed by primary repair. After the procedure, group 1 was determined as the control group and received no medication. Group 2 received 2.03 mg/kg rivaroxaban daily via gastric lavage once daily, and group 3 was given subcutaneous 114 IU AXa nadroparin calcium once daily for 28 days. After euthanization, the degrees of inflammation, neovascularization, fibroblastic activity, and collagen fiber sequencing were examined and scored for histopathological evaluation. The Statistical Package for Social Science (SPSS) version 21.0 for Windows software (SPSS, Inc., Chicago, Illinois, United States) was used for all statistical analyses. The number of inflammatory cells, capillary vessels, and fibroblasts, which met the parametric tests' assumptions, were compared between three independent groups by one-way analysis of variance. The significance level was set at p- value < 0.05. Results Histological examination of the group 1 sample showed the presence of inflammatory cells, an increase in the number of fibroblasts, and sequencing of collagen fibers scattered. The presence of inflammatory cells, remarkable increases in the number of fibroblasts, the presence of mature collagen fibers, and regular sequencing of collagen fibers regular were shown in groups 2 and 3. There were statistically significant differences between the groups regarding the number of inflammatory cells and fibroblasts. In group 2, the number of inflammatory cells was lower than in groups 1 and 3. Elsewhere, the number of fibroblasts was higher in group 1 compared than in groups 2 and 3. Conclusion Both rivaroxaban and nadroparin calcium in their daily dosage have a beneficial effect on Achilles tendon healing.
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Affiliation(s)
- Suleyman Altun
- Department of Orthopaedics and Traumatology, Baskent University Faculty of Medicine, Baskent University Hospital, Çankaya/Ankara, Turkey
| | - Mehmet Sukru Sahin
- Department of Orthopaedics and Traumatology, Baskent University Alanya Research and Practice Center, Alanya/Antalya, Turkey
| | - Gokhan Çakmak
- Department of Orthopaedics and Traumatology, Baskent University Alanya Research and Practice Center, Alanya/Antalya, Turkey
| | - Kemal Gokkus
- Department of Orthopaedics and Traumatology, Baskent University Alanya Research and Practice Center, Alanya/Antalya, Turkey
| | - Aysen Terzi
- Department of Orthopaedics and Traumatology, Baskent University Faculty of Medicine, Baskent University Hospital, Çankaya/Ankara, Turkey
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Xu H, Zhu Y, Xu J, Tong W, Hu S, Chen Y, Deng S, Yao H, Li J, Lee C, Chan HF. Injectable bioactive glass/sodium alginate hydrogel with immunomodulatory and angiogenic properties for enhanced tendon healing. Bioeng Transl Med 2023; 8:e10345. [PMID: 36684098 PMCID: PMC9842034 DOI: 10.1002/btm2.10345] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 04/17/2022] [Accepted: 04/29/2022] [Indexed: 01/25/2023] Open
Abstract
Tendon healing is a complex process involving inflammation, proliferation, and remodeling, eventually achieving a state of hypocellularity and hypovascularity. Currently, few treatments can satisfactorily restore the structure and function of native tendon. Bioactive glass (BG) has been shown to possess immunomodulatory and angiogenic properties. In this study, we investigated whether an injectable hydrogel fabricated of BG and sodium alginate (SA) could be applied to enhance tenogenesis following suture repair of injured tendon. We demonstrated that BG/SA hydrogel significantly accelerated tenogenesis without inducing heterotopic ossification based on histological analysis. The therapeutic effect could attribute to increased angiogenesis and M1 to M2 phenotypic switch of macrophages within 7 days post-surgery. Morphological characterization demonstrated that BG/SA hydrogel partially reverted the pathological changes of Achilles tendon, including increased length and cross-sectional area (CSA). Finally, biomechanical test showed that BG/SA hydrogel significantly improved ultimate load, failure stress, and tensile modulus of the repaired tendon. In conclusion, administration of an injectable BG/SA hydrogel can be a novel and promising therapeutic approach to augment Achilles tendon healing in conjunction with surgical intervention.
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Affiliation(s)
- Hongtao Xu
- Musculoskeletal Research Laboratory, Department of Orthopedics and TraumatologyThe Chinese University of Hong KongHong Kong SARChina
- Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong SARChina
- Department of OrthopedicsThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
| | - Yanlun Zhu
- Institute for Tissue Engineering and Regenerative Medicine, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina
- Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina
| | - Jiankun Xu
- Musculoskeletal Research Laboratory, Department of Orthopedics and TraumatologyThe Chinese University of Hong KongHong Kong SARChina
- Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong SARChina
| | - Wenxue Tong
- Musculoskeletal Research Laboratory, Department of Orthopedics and TraumatologyThe Chinese University of Hong KongHong Kong SARChina
- Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong SARChina
| | - Shiwen Hu
- Musculoskeletal Research Laboratory, Department of Orthopedics and TraumatologyThe Chinese University of Hong KongHong Kong SARChina
- Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong SARChina
- School of Materials Science and EngineeringLanzhou University of TechnologyLanzhouChina
| | - Yi‐Fan Chen
- The Ph.D. Program for Translational Medicine, College of Medical Science and TechnologyTaipei Medical UniversityTaipeiTaiwan
- Graduate Institute of Translational Medicine, College of Medical Science and TechnologyTaipei Medical UniversityTaipeiTaiwan
- International Ph.D. Program for Translational Science, College of Medical Science and TechnologyTaipei Medical UniversityTaipeiTaiwan
- Master Program in Clinical Genomics and Proteomics, School of PharmacyTaipei Medical UniversityTaipeiTaiwan
| | - Shuai Deng
- Institute for Tissue Engineering and Regenerative Medicine, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina
- Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina
| | - Hao Yao
- Musculoskeletal Research Laboratory, Department of Orthopedics and TraumatologyThe Chinese University of Hong KongHong Kong SARChina
- Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong SARChina
| | - Jie Li
- Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjingChina
| | - Chien‐Wei Lee
- Center for Translational Genomics ResearchChina Medical University Hospital, China Medical UniversityTaichungTaiwan
| | - Hon Fai Chan
- Institute for Tissue Engineering and Regenerative Medicine, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina
- Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina
- Hong Kong Branch of CAS Center for Excellence in Animal Evolution and GeneticsThe Chinese University of Hong KongHong Kong SARChina
- Center for Neuromusculoskeletal Restorative MedicineHong Kong Science ParkHong Kong SARChina
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11
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Ferracini R, Artiaco S, Daghino W, Falco M, Gallo A, Garibaldi R, Tiraboschi E, Guidotti C, Bistolfi A. Microfragmented Adipose Tissue (M-FATS) for Improved Healing of Surgically Repaired Achilles Tendon Tears: A Preliminary Study. Foot Ankle Spec 2022; 15:472-478. [PMID: 33241717 DOI: 10.1177/1938640020974557] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
INTRODUCTION Tendon healing is a complicated process that results in inferior structural and functional properties when compared with healthy tendon; the purpose of this study was to assess the effects of the adjunct of microfragmented adipose tissue (M-FATS) after the suture of a series of Achilles tendons. METHODS After complete Achilles tendon tear, 8 patients underwent open suture repair in conjunction with perilesional application of a preparation of M-FATS rich in mesenchymal stem cells. Results were compared with a similar group of patients treated with conventional open suture. Outcomes were evaluated based on range of motion, functional recovery, and complications according to the American Orthopedic Foot and Ankle Society (AOFAS) score and Foot and Ankle Disability Index (FADI). Achilles tendons were examined by ultrasound (US) at 3 months. RESULTS The AOFAS and FADI scores showed no differences between the 2 groups. US evaluation showed quicker tendon remodeling in the M-FATS group. Adverse events were not documented for both procedures. CONCLUSIONS The combined application of derived M-FATS for tendon rupture is safe and presents new possibilities for enhanced healing. LEVELS OF EVIDENCE Level IIIb: Case control study.
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Affiliation(s)
- Riccardo Ferracini
- Orthopaedic Unit, Koelliker Hospital, Turin, Italy.,Orthopaedic Clinic, University of Genova, Italy
| | - Stefano Artiaco
- Department of Orthopaedics, Traumatology and Rehabilitation, Hospital Città della Salute e della Scienza, Turin, Italy
| | - Walter Daghino
- Department of Orthopaedics, Traumatology and Rehabilitation, Hospital Città della Salute e della Scienza, Turin, Italy
| | - Mara Falco
- Radiodiagnostic Cellini Humanitas, Turin, Italy
| | - Alessandra Gallo
- Diagnostic Imaging and Radiotherapy, Koelliker Hospital, Turin, Italy
| | | | | | - Claudio Guidotti
- Department of Orthopaedics, Traumatology and Rehabilitation, Hospital Città della Salute e della Scienza, Turin, Italy
| | - Alessandro Bistolfi
- Department of Orthopaedics, Traumatology and Rehabilitation, Hospital Città della Salute e della Scienza, Turin, Italy
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12
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Effects and Mechanism of Particulate Matter on Tendon Healing Based on Integrated Analysis of DNA Methylation and RNA Sequencing Data in a Rat Model. Int J Mol Sci 2022; 23:ijms23158170. [PMID: 35897746 PMCID: PMC9332732 DOI: 10.3390/ijms23158170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 07/22/2022] [Accepted: 07/22/2022] [Indexed: 02/01/2023] Open
Abstract
Exposure to particulate matter (PM) has been linked with the severity of various diseases. To date, there is no study on the relationship between PM exposure and tendon healing. Open Achilles tenotomy of 20 rats was performed. The animals were divided into two groups according to exposure to PM: a PM group and a non-PM group. After 6 weeks of PM exposure, the harvest and investigations of lungs, blood samples, and Achilles tendons were performed. Compared to the non-PM group, the white blood cell count and tumor necrosis factor-alpha expression in the PM group were significantly higher. The Achilles tendons in PM group showed significantly increased inflammatory outcomes. A TEM analysis showed reduced collagen fibrils in the PM group. A biomechanical analysis demonstrated that the load to failure value was lower in the PM group. An upregulation of the gene encoding cyclic AMP response element-binding protein (CREB) was detected in the PM group by an integrated analysis of DNA methylation and RNA sequencing data, as confirmed via a Western blot analysis showing significantly elevated levels of phosphorylated CREB. In summary, PM exposure caused a deleterious effect on tendon healing. The molecular data indicate that the action mechanism of PM may be associated with upregulated CREB signaling.
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13
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Song JH, Kang C, Han SY, Park WH, Kim MH, Moon JH, Tae JY, Park HY, Yoo IH, Park JH, Yeo YH, Kim DY. Comparative analysis of Achilles tendon healing outcomes after open tenotomy versus percutaneous tenotomy: An experimental study in rats. J Orthop Res 2022; 40:1446-1456. [PMID: 34370341 DOI: 10.1002/jor.25159] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 06/25/2021] [Accepted: 07/30/2021] [Indexed: 02/04/2023]
Abstract
There is growing interest in conservative treatment of Achilles tendon rupture. However, the majority of experimental studies of Achilles tendon have been performed by open tenotomy. More appropriate model of conservative treatment of Achilles tendon rupture is required. We performed an experimental study to evaluate whether outcomes differ between open tenotomy and percutaneous tenotomy of the Achilles tendon in rats. The Achilles tendons of 48 rats were transected. The animals were divided into two groups according to surgical technique: open tenotomy or microscopy-assisted percutaneous tenotomy. After 1, 2, and 4 weeks, functional, biomechanical, and histological analyses were performed. Western blot was performed for quantitative molecular analysis at 1 week. The Achilles functional index was superior in the percutaneous tenotomy group, compared with the open tenotomy group, at 1 week. The cross-sectional area was significantly larger in the percutaneous tenotomy group than in the open tenotomy group at 4 weeks. Relative to the native tendons, load to failure and stiffness yielded comparable results at 2 weeks in the percutaneous tenotomy group and at 4 weeks in the open tenotomy group. The histological score was significantly better in the percutaneous tenotomy group than in the open tenotomy group at 1 week. At 1 week, interleukin-1β expression in the open tenotomy group was higher than in the percutaneous tenotomy group. In summary, Achilles tendon healing was substantially affected by the tenotomy method. We presume that our percutaneous tenotomy method might constitute a useful experimental animal model for conservative treatment of Achilles tendon rupture.
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Affiliation(s)
- Jae H Song
- Department of Orthopedic Surgery, Konyang University Hospital, Daejeon, Republic of Korea
| | - Chan Kang
- Department of Orthopedic Surgery, Regional Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - Seung Y Han
- Department of Anatomy, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Won H Park
- Department of Advanced Organic Materials and Textile Engineering System, Chungnam National University, Daejeon, Republic of Korea
| | - Min H Kim
- Department of Biomedical Engineering, Purdue School of Engineering & Technology, Indiana University-Purdue University, Indianapolis, Indiana, USA
| | - Ji H Moon
- Department of Anatomy, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Jung Y Tae
- Department of Medicine, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Hyeon Y Park
- Department of Occupational Therapy, Konyang University, Daejeon, Republic of Korea
| | - In H Yoo
- Department of Occupational Therapy, Konyang University, Daejeon, Republic of Korea
| | - Jong H Park
- Department of Biomedical Material, College of Medical Engineering, Konyang University, Daejeon, Republic of Korea
| | - Yong H Yeo
- Department of Advanced Organic Materials and Textile Engineering System, Chungnam National University, Daejeon, Republic of Korea
| | - Dae Y Kim
- Department of Orthopedic Surgery, Konyang University Hospital, Daejeon, Republic of Korea
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14
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Cetik RM, Yabanoglu Ciftci S, Arica B, Baysal I, Akarca Dizakar SO, Erbay Elibol FK, Gencer A, Demir T, Ayvaz M. Evaluation of the Effects of Transforming Growth Factor-Beta 3 (TGF-β3) Loaded Nanoparticles on Healing in a Rat Achilles Tendon Injury Model. Am J Sports Med 2022; 50:1066-1077. [PMID: 35188807 DOI: 10.1177/03635465211073148] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Achilles tendon (AT) midsubstance injuries may heal suboptimally, especially in athletes. Transforming growth factor-beta 3 (TGF-β3) shows promise because of its recently discovered tendinogenic effects. Using poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles (NPs) may enhance the results by a sustained-release effect. HYPOTHESIS The application of TGF-β3 will enhance AT midsubstance healing, and the NP form will achieve better outcomes. STUDY DESIGN Controlled laboratory study. METHODS A total of 80 rats underwent unilateral AT transection and were divided into 4 groups: (1) control (C); (2) empty chitosan film (Ch); (3) chitosan film containing free TGF-β3 (ChT); and (4) chitosan film containing TGF-β3-loaded NPs (ChN). The animals were sacrificed at 3 and 6 weeks. Tendons were evaluated for morphology (length and cross-sectional area [CSA]), biomechanics (maximum load, stress, stiffness, and elastic modulus), histology, immunohistochemical quantification (types I and III collagen [COL1 and COL3]), and gene expression (COL1A1, COL3A1, scleraxis, and tenomodulin). RESULTS Morphologically, at 3 weeks, ChT (15 ± 2.7 mm) and ChN (15.6 ± 1.6 mm) were shorter than C (17.6 ± 1.8 mm) (P = .019 and = .004, respectively). At 6 weeks, the mean CSA of ChN (10.4 ± 1.9 mm2) was similar to that of intact tendons (6.4 ± 1.1 mm2) (P = .230), while the other groups were larger. Biomechanically, at 3 weeks, ChT (42.8 ± 4.9 N) had a higher maximum load than C (27 ± 9.1 N; P = .004) and Ch (29.2 ± 5.7 N; P = .005). At 6 weeks, ChN (26.9 ± 3.9 MPa) had similar maximum stress when compared with intact tendons (34.1 ± 7.8 MPa) (P = .121); the other groups were significantly lower. Histologically, at 6 weeks, the mean Movin score of ChN (4.5 ± 1.5) was lower than that of ChT (6.3 ± 1.8). Immunohistochemically, ChN had higher COL3 (1.469 ± 0.514) at 3 weeks and lower COL1 (1.129 ± 0.368) at 6 weeks. COL1A1 gene expression was higher in ChT and ChN at 3 weeks, but COL3A1 gene expression was higher in ChN. CONCLUSION The application of TGF-β3 had a positive effect on AT midsubstance healing, and the sustained-release NP form improved the outcomes, more specifically accelerating the remodeling process. CLINICAL RELEVANCE This study demonstrated the effectiveness of TGF-β3 on tendon healing on a rat model, which is an important step toward clinical use. The novel method of using PLGA-b-PEG NPs as a drug-delivery system with sustained-release properties had promising results.
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Affiliation(s)
- Riza Mert Cetik
- Hacettepe University Faculty of Medicine, Department of Orthopedics and Traumatology, Ankara, Turkey
| | | | - Betul Arica
- Hacettepe University Faculty of Pharmacy, Department of Pharmaceutical Technology, Ankara, Turkey
| | - Ipek Baysal
- Hacettepe University Vocational School of Health Services, Ankara, Turkey
| | | | - Fatma Kubra Erbay Elibol
- TOBB ETÜ University of Economics and Technology, Department of Biomedical Engineering, Ankara, Turkey
| | - Ayse Gencer
- Hacettepe University Faculty of Pharmacy, Department of Pharmaceutical Technology, Ankara, Turkey
| | - Teyfik Demir
- TOBB ETÜ University of Economics and Technology, Department of Mechanical Engineering, Ankara, Turkey
| | - Mehmet Ayvaz
- Hacettepe University Faculty of Medicine, Department of Orthopedics and Traumatology, Ankara, Turkey
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15
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Russo V, El Khatib M, Prencipe G, Cerveró-Varona A, Citeroni MR, Mauro A, Berardinelli P, Faydaver M, Haidar-Montes AA, Turriani M, Di Giacinto O, Raspa M, Scavizzi F, Bonaventura F, Liverani L, Boccaccini AR, Barboni B. Scaffold-Mediated Immunoengineering as Innovative Strategy for Tendon Regeneration. Cells 2022; 11:cells11020266. [PMID: 35053383 PMCID: PMC8773518 DOI: 10.3390/cells11020266] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 01/06/2022] [Accepted: 01/10/2022] [Indexed: 12/13/2022] Open
Abstract
Tendon injuries are at the frontier of innovative approaches to public health concerns and sectoral policy objectives. Indeed, these injuries remain difficult to manage due to tendon’s poor healing ability ascribable to a hypo-cellularity and low vascularity, leading to the formation of a fibrotic tissue affecting its functionality. Tissue engineering represents a promising solution for the regeneration of damaged tendons with the aim to stimulate tissue regeneration or to produce functional implantable biomaterials. However, any technological advancement must take into consideration the role of the immune system in tissue regeneration and the potential of biomaterial scaffolds to control the immune signaling, creating a pro-regenerative environment. In this context, immunoengineering has emerged as a new discipline, developing innovative strategies for tendon injuries. It aims at designing scaffolds, in combination with engineered bioactive molecules and/or stem cells, able to modulate the interaction between the transplanted biomaterial-scaffold and the host tissue allowing a pro-regenerative immune response, therefore hindering fibrosis occurrence at the injury site and guiding tendon regeneration. Thus, this review is aimed at giving an overview on the role exerted from different tissue engineering actors in leading immunoregeneration by crosstalking with stem and immune cells to generate new paradigms in designing regenerative medicine approaches for tendon injuries.
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Affiliation(s)
- Valentina Russo
- Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy; (V.R.); (M.E.K.); (A.C.-V.); (M.R.C.); (A.M.); (P.B.); (M.F.); (A.A.H.-M.); (M.T.); (O.D.G.); (B.B.)
| | - Mohammad El Khatib
- Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy; (V.R.); (M.E.K.); (A.C.-V.); (M.R.C.); (A.M.); (P.B.); (M.F.); (A.A.H.-M.); (M.T.); (O.D.G.); (B.B.)
| | - Giuseppe Prencipe
- Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy; (V.R.); (M.E.K.); (A.C.-V.); (M.R.C.); (A.M.); (P.B.); (M.F.); (A.A.H.-M.); (M.T.); (O.D.G.); (B.B.)
- Correspondence:
| | - Adrián Cerveró-Varona
- Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy; (V.R.); (M.E.K.); (A.C.-V.); (M.R.C.); (A.M.); (P.B.); (M.F.); (A.A.H.-M.); (M.T.); (O.D.G.); (B.B.)
| | - Maria Rita Citeroni
- Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy; (V.R.); (M.E.K.); (A.C.-V.); (M.R.C.); (A.M.); (P.B.); (M.F.); (A.A.H.-M.); (M.T.); (O.D.G.); (B.B.)
| | - Annunziata Mauro
- Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy; (V.R.); (M.E.K.); (A.C.-V.); (M.R.C.); (A.M.); (P.B.); (M.F.); (A.A.H.-M.); (M.T.); (O.D.G.); (B.B.)
| | - Paolo Berardinelli
- Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy; (V.R.); (M.E.K.); (A.C.-V.); (M.R.C.); (A.M.); (P.B.); (M.F.); (A.A.H.-M.); (M.T.); (O.D.G.); (B.B.)
| | - Melisa Faydaver
- Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy; (V.R.); (M.E.K.); (A.C.-V.); (M.R.C.); (A.M.); (P.B.); (M.F.); (A.A.H.-M.); (M.T.); (O.D.G.); (B.B.)
| | - Arlette A. Haidar-Montes
- Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy; (V.R.); (M.E.K.); (A.C.-V.); (M.R.C.); (A.M.); (P.B.); (M.F.); (A.A.H.-M.); (M.T.); (O.D.G.); (B.B.)
| | - Maura Turriani
- Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy; (V.R.); (M.E.K.); (A.C.-V.); (M.R.C.); (A.M.); (P.B.); (M.F.); (A.A.H.-M.); (M.T.); (O.D.G.); (B.B.)
| | - Oriana Di Giacinto
- Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy; (V.R.); (M.E.K.); (A.C.-V.); (M.R.C.); (A.M.); (P.B.); (M.F.); (A.A.H.-M.); (M.T.); (O.D.G.); (B.B.)
| | - Marcello Raspa
- Institute of Biochemistry and Cellular Biology (IBBC), Council of National Research (CNR), Campus International Development (EMMA-INFRAFRONTIER-IMPC), 00015 Monterotondo Scalo, Italy; (M.R.); (F.S.); (F.B.)
| | - Ferdinando Scavizzi
- Institute of Biochemistry and Cellular Biology (IBBC), Council of National Research (CNR), Campus International Development (EMMA-INFRAFRONTIER-IMPC), 00015 Monterotondo Scalo, Italy; (M.R.); (F.S.); (F.B.)
| | - Fabrizio Bonaventura
- Institute of Biochemistry and Cellular Biology (IBBC), Council of National Research (CNR), Campus International Development (EMMA-INFRAFRONTIER-IMPC), 00015 Monterotondo Scalo, Italy; (M.R.); (F.S.); (F.B.)
| | - Liliana Liverani
- Department of Materials Science and Engineering, Institute of Biomaterials, University of Erlangen-Nuremberg, 91058 Erlangen, Germany; (L.L.); (A.R.B.)
| | - Aldo R. Boccaccini
- Department of Materials Science and Engineering, Institute of Biomaterials, University of Erlangen-Nuremberg, 91058 Erlangen, Germany; (L.L.); (A.R.B.)
| | - Barbara Barboni
- Unit of Basic and Applied Sciences, Faculty of Biosciences and Agro-Food and Environmental Technologies, University of Teramo, 64100 Teramo, Italy; (V.R.); (M.E.K.); (A.C.-V.); (M.R.C.); (A.M.); (P.B.); (M.F.); (A.A.H.-M.); (M.T.); (O.D.G.); (B.B.)
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16
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Lakhani A, Sharma E, Kapila A, Khatri K. Known data on applied regenerative medicine in tendon healing. Bioinformation 2021; 17:514-527. [PMID: 34602779 PMCID: PMC8450149 DOI: 10.6026/97320630017514] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/31/2021] [Accepted: 04/29/2021] [Indexed: 12/03/2022] Open
Abstract
Tendons and ligaments are important structures in the musculoskeletal system. Ligaments connect various bones and provide stability in complex movements of joints in the knee. Tendon is made of dense connective tissue and transmits the force of contraction from muscle to bone. They are injured due to direct trauma in sports or roadside accidents. Tendon healing after repair is often poor due to the formation of fibro vascular scar tissues with low mechanical property. Regenerative techniques such as PRP (platelet-rich plasma), stem cells, scaffolds, gene therapy, cell sheets, and scaffolds help augment repair and regenerate tissue in this context. Therefore, it is of interest to document known data (repair process, tissue regeneration, mechanical strength, and clinical outcome) on applied regenerative medicine in tendon healing.
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Affiliation(s)
- Amit Lakhani
- Dr Br Ambedkar State Institute of Medical Sciences, Mohali Punjab, India
| | - Ena Sharma
- Maharishi Markandeshwar College of Dental Sciences and Hospital Mullana, Ambala, Haryana, India
| | | | - Kavin Khatri
- All India Institute of Medical Sciences, Bathinda, Punjab, India
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17
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Cunha FB, Pomini KT, Plepis AMDG, Martins VDCA, Machado EG, de Moraes R, Munhoz MDAES, Machado MVR, Duarte MAH, Alcalde MP, Buchaim DV, Buchaim RL, Fernandes VAR, Pereira EDSBM, Pelegrine AA, da Cunha MR. In Vivo Biological Behavior of Polymer Scaffolds of Natural Origin in the Bone Repair Process. Molecules 2021; 26:1598. [PMID: 33805847 PMCID: PMC8002007 DOI: 10.3390/molecules26061598] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 03/09/2021] [Indexed: 12/15/2022] Open
Abstract
Autologous bone grafts, used mainly in extensive bone loss, are considered the gold standard treatment in regenerative medicine, but still have limitations mainly in relation to the amount of bone available, donor area, morbidity and creation of additional surgical area. This fact encourages tissue engineering in relation to the need to develop new biomaterials, from sources other than the individual himself. Therefore, the present study aimed to investigate the effects of an elastin and collagen matrix on the bone repair process in critical size defects in rat calvaria. The animals (Wistar rats, n = 30) were submitted to a surgical procedure to create the bone defect and were divided into three groups: Control Group (CG, n = 10), defects filled with blood clot; E24/37 Group (E24/37, n = 10), defects filled with bovine elastin matrix hydrolyzed for 24 h at 37 °C and C24/25 Group (C24/25, n = 10), defects filled with porcine collagen matrix hydrolyzed for 24 h at 25 °C. Macroscopic and radiographic analyses demonstrated the absence of inflammatory signs and infection. Microtomographical 2D and 3D images showed centripetal bone growth and restricted margins of the bone defect. Histologically, the images confirmed the pattern of bone deposition at the margins of the remaining bone and without complete closure by bone tissue. In the morphometric analysis, the groups E24/37 and C24/25 (13.68 ± 1.44; 53.20 ± 4.47, respectively) showed statistically significant differences in relation to the CG (5.86 ± 2.87). It was concluded that the matrices used as scaffolds are biocompatible and increase the formation of new bone in a critical size defect, with greater formation in the polymer derived from the intestinal serous layer of porcine origin (C24/25).
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Affiliation(s)
- Fernando Bento Cunha
- Department of Morphology and Pathology, Medical College of Jundiai, Jundiaí, São Paulo 13202-550, SP, Brazil; (F.B.C.); (E.G.M.); (R.d.M.); (M.d.A.eS.M.); (M.V.R.M.); (V.A.R.F.); (M.R.d.C.)
- Interunit Postgraduate Program in Bioengineering (EESC/FMRP/IQSC), University of São Paulo (USP), São Carlos 13566-590, SP, Brazil;
| | - Karina Torres Pomini
- Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo (FOB/USP), Bauru 17012-901, SP, Brazil;
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Marília 17525-902, SP, Brazil;
| | - Ana Maria de Guzzi Plepis
- Interunit Postgraduate Program in Bioengineering (EESC/FMRP/IQSC), University of São Paulo (USP), São Carlos 13566-590, SP, Brazil;
- São Carlos Institute of Chemistry, University of São Paulo, USP, São Carlos 13566-590, SP, Brazil;
| | | | - Eduardo Gomes Machado
- Department of Morphology and Pathology, Medical College of Jundiai, Jundiaí, São Paulo 13202-550, SP, Brazil; (F.B.C.); (E.G.M.); (R.d.M.); (M.d.A.eS.M.); (M.V.R.M.); (V.A.R.F.); (M.R.d.C.)
- Interunit Postgraduate Program in Bioengineering (EESC/FMRP/IQSC), University of São Paulo (USP), São Carlos 13566-590, SP, Brazil;
| | - Renato de Moraes
- Department of Morphology and Pathology, Medical College of Jundiai, Jundiaí, São Paulo 13202-550, SP, Brazil; (F.B.C.); (E.G.M.); (R.d.M.); (M.d.A.eS.M.); (M.V.R.M.); (V.A.R.F.); (M.R.d.C.)
- Interunit Postgraduate Program in Bioengineering (EESC/FMRP/IQSC), University of São Paulo (USP), São Carlos 13566-590, SP, Brazil;
| | - Marcelo de Azevedo e Souza Munhoz
- Department of Morphology and Pathology, Medical College of Jundiai, Jundiaí, São Paulo 13202-550, SP, Brazil; (F.B.C.); (E.G.M.); (R.d.M.); (M.d.A.eS.M.); (M.V.R.M.); (V.A.R.F.); (M.R.d.C.)
- Interunit Postgraduate Program in Bioengineering (EESC/FMRP/IQSC), University of São Paulo (USP), São Carlos 13566-590, SP, Brazil;
| | - Michela Vanessa Ribeiro Machado
- Department of Morphology and Pathology, Medical College of Jundiai, Jundiaí, São Paulo 13202-550, SP, Brazil; (F.B.C.); (E.G.M.); (R.d.M.); (M.d.A.eS.M.); (M.V.R.M.); (V.A.R.F.); (M.R.d.C.)
| | - Marco Antonio Hungaro Duarte
- Department of Dentistry, Endodontics and Dental Materials, Bauru School of Dentistry, University of São Paulo (FOB/USP), Bauru 17012-901, SP, Brazil;
| | - Murilo Priori Alcalde
- Department of Health Science, Unisagrado University Center, Bauru 17011-160, SP, Brazil;
| | - Daniela Vieira Buchaim
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Marília 17525-902, SP, Brazil;
- Medical School, University Center of Adamantina (UniFAI), Adamantina 17800-000, SP, Brazil
| | - Rogério Leone Buchaim
- Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo (FOB/USP), Bauru 17012-901, SP, Brazil;
| | - Victor Augusto Ramos Fernandes
- Department of Morphology and Pathology, Medical College of Jundiai, Jundiaí, São Paulo 13202-550, SP, Brazil; (F.B.C.); (E.G.M.); (R.d.M.); (M.d.A.eS.M.); (M.V.R.M.); (V.A.R.F.); (M.R.d.C.)
- Laboratory of Anatomy, University Center Our Lady of Patronage (CEUNSP), University of South Cruise, Itu 13300-200, SP, Brazil
| | | | - André Antonio Pelegrine
- Research Institute, Postgraduate Program, São Leopoldo Mandic, School of Dentistry, Campinas 13045-755, SP, Brazil;
| | - Marcelo Rodrigues da Cunha
- Department of Morphology and Pathology, Medical College of Jundiai, Jundiaí, São Paulo 13202-550, SP, Brazil; (F.B.C.); (E.G.M.); (R.d.M.); (M.d.A.eS.M.); (M.V.R.M.); (V.A.R.F.); (M.R.d.C.)
- Interunit Postgraduate Program in Bioengineering (EESC/FMRP/IQSC), University of São Paulo (USP), São Carlos 13566-590, SP, Brazil;
- Laboratory of Anatomy, University Center Our Lady of Patronage (CEUNSP), University of South Cruise, Itu 13300-200, SP, Brazil
- Research Institute, Postgraduate Program, São Leopoldo Mandic, School of Dentistry, Campinas 13045-755, SP, Brazil;
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Sun Y, Kwak JM, Kholinne E, Koh KH, Tan J, Jeon IH. Subacromial bursal preservation can enhance rotator cuff tendon regeneration: a comparative rat supraspinatus tendon defect model study. J Shoulder Elbow Surg 2021; 30:401-407. [PMID: 32534844 DOI: 10.1016/j.jse.2020.05.025] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 05/08/2020] [Accepted: 05/18/2020] [Indexed: 02/01/2023]
Abstract
BACKGROUND The role of subacromial bursa in rotator cuff surgery is unknown. This study aimed to assess the subacromial bursa's role in the healing of supraspinatus tendon injury in a rat model. METHODS Twenty-three male Sprague-Dawley rats (9 weeks old; weight, approximately 296 g) were used in this study. Three rats used as biomechanical study controls were killed at 12 weeks of age. A supraspinatus tendon defect was made bilaterally in 20 rats, whereas an additional subacromial bursa sectioning was performed on the left side. Six rats were killed for biomechanical testing and 4 were killed for histologic observation at 3 and 9 weeks, respectively. RESULTS The regenerated tendon in the bursal preservation group showed significantly superior biomechanical properties in maximum load to failure at 3 and 9 weeks and stiffness at 9 weeks after surgery compared with the bursal removal group. The modified Bonar scale scores showed better regenerated supraspinatus tendons in the bursal preservation group. CONCLUSION The present study found that the subacromial bursa plays an important role in rotator cuff regeneration in this rat supraspinatus injury model. Extensive bursectomy of the subacromial bursa may not be recommended in rotator cuff repair surgery, though future in vivo human studies are needed to confirm these observations.
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Affiliation(s)
- Yucheng Sun
- Department of Hand Surgery, Affiliated Hospital of Nantong University, College of Medicine, University of Nantong, Nantong, China; Department of Orthopedic Surgery, ASAN Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea
| | - Jae-Man Kwak
- Department of Orthopedic Surgery, ASAN Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea
| | - Erica Kholinne
- Department of Orthopedic Surgery, ASAN Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea; Department of Orthopedic Surgery, St. Carolus Hospital, Jakarta, Indonesia
| | - Kyoung-Hwan Koh
- Department of Orthopedic Surgery, ASAN Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea
| | - Jun Tan
- Department of Hand Surgery, Affiliated Hospital of Nantong University, College of Medicine, University of Nantong, Nantong, China
| | - In-Ho Jeon
- Department of Orthopedic Surgery, ASAN Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.
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Zhang BY, Xu P, Luo Q, Song GB. Proliferation and tenogenic differentiation of bone marrow mesenchymal stem cells in a porous collagen sponge scaffold. World J Stem Cells 2021; 13:115-127. [PMID: 33584983 PMCID: PMC7859984 DOI: 10.4252/wjsc.v13.i1.115] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 11/02/2020] [Accepted: 11/17/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Collagen is one of the most commonly used natural biomaterials for tendon tissue engineering. One of the possible practical ways to further enhance tendon repair is to combine a porous collagen sponge scaffold with a suitable growth factor or cytokine that has an inherent ability to promote the recruitment, proliferation, and tenogenic differentiation of cells. However, there is an incomplete understanding of which growth factors are sufficient and optimal for the tenogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) in a collagen sponge-based 3D culture system.
AIM To identify one or more ideal growth factors that benefit the proliferation and tenogenic differentiation of rat BMSCs in a porous collagen sponge scaffold.
METHODS We constructed a 3D culture system based on a type I collagen sponge scaffold. The surface topography of the collagen sponge scaffold was observed by scanning electron microscopy. Primary BMSCs were isolated from Sprague-Dawley rats. Cell survival on the surfaces of the scaffolds with different growth factors was assessed by live/dead assay and CCK-8 assay. The mRNA and protein expression levels were confirmed by quantitative real-time polymerase chain reaction and Western blot, respectively. The deposited collagen was assessed by Sirius Red staining.
RESULTS Transforming growth factor β1 (TGF-β1) showed great promise in the tenogenic differentiation of BMSCs compared to growth differentiation factor 7 (GDF-7) and insulin-like growth factor 1 (IGF-1) in both the 2D and 3D cultures, and the 3D culture enhanced the differentiation of BMSCs into tenocytes well beyond the level of induction in the 2D culture after TGF-β1 treatment. In the 2D culture, the proliferation of the BMSCs showed no significant changes compared to the control group after TGF-β1, IGF-1, or GDF-7 treatment. However, TGF-β1 and GDF-7 could increase the cell proliferation in the 3D culture. Strangely, we also found more dead cells in the BMSC-collagen sponge constructs that were treated with TGF-β1. Moreover, TGF-β1 promoted more collagen deposition in both the 2D and 3D cultures.
CONCLUSION Collagen sponge-based 3D culture with TGF-β1 enhances the responsiveness of the proliferation and tenogenic differentiation of rat BMSCs.
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Affiliation(s)
- Bing-Yu Zhang
- Department of College of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing 400065, China
| | - Pu Xu
- Department of College of Bioengineering, Chongqing University, Chongqing 400030, China
| | - Qing Luo
- Department of College of Bioengineering, Chongqing University, Chongqing 400030, China
| | - Guan-Bin Song
- Department of College of Bioengineering, Chongqing University, Chongqing 400030, China
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20
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Citeroni MR, Ciardulli MC, Russo V, Della Porta G, Mauro A, El Khatib M, Di Mattia M, Galesso D, Barbera C, Forsyth NR, Maffulli N, Barboni B. In Vitro Innovation of Tendon Tissue Engineering Strategies. Int J Mol Sci 2020; 21:E6726. [PMID: 32937830 PMCID: PMC7555358 DOI: 10.3390/ijms21186726] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 09/06/2020] [Accepted: 09/07/2020] [Indexed: 12/12/2022] Open
Abstract
Tendinopathy is the term used to refer to tendon disorders. Spontaneous adult tendon healing results in scar tissue formation and fibrosis with suboptimal biomechanical properties, often resulting in poor and painful mobility. The biomechanical properties of the tissue are negatively affected. Adult tendons have a limited natural healing capacity, and often respond poorly to current treatments that frequently are focused on exercise, drug delivery, and surgical procedures. Therefore, it is of great importance to identify key molecular and cellular processes involved in the progression of tendinopathies to develop effective therapeutic strategies and drive the tissue toward regeneration. To treat tendon diseases and support tendon regeneration, cell-based therapy as well as tissue engineering approaches are considered options, though none can yet be considered conclusive in their reproduction of a safe and successful long-term solution for full microarchitecture and biomechanical tissue recovery. In vitro differentiation techniques are not yet fully validated. This review aims to compare different available tendon in vitro differentiation strategies to clarify the state of art regarding the differentiation process.
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Affiliation(s)
- Maria Rita Citeroni
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (V.R.); (A.M.); (M.E.K.); (M.D.M.); (B.B.)
| | - Maria Camilla Ciardulli
- Department of Medicine, Surgery and Dentistry, University of Salerno, Via S. Allende, 84081 Baronissi (SA), Italy; (M.C.C.); (G.D.P.); (N.M.)
| | - Valentina Russo
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (V.R.); (A.M.); (M.E.K.); (M.D.M.); (B.B.)
| | - Giovanna Della Porta
- Department of Medicine, Surgery and Dentistry, University of Salerno, Via S. Allende, 84081 Baronissi (SA), Italy; (M.C.C.); (G.D.P.); (N.M.)
- Interdepartment Centre BIONAM, Università di Salerno, via Giovanni Paolo I, 84084 Fisciano (SA), Italy
| | - Annunziata Mauro
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (V.R.); (A.M.); (M.E.K.); (M.D.M.); (B.B.)
| | - Mohammad El Khatib
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (V.R.); (A.M.); (M.E.K.); (M.D.M.); (B.B.)
| | - Miriam Di Mattia
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (V.R.); (A.M.); (M.E.K.); (M.D.M.); (B.B.)
| | - Devis Galesso
- Fidia Farmaceutici S.p.A., via Ponte della Fabbrica 3/A, 35031 Abano Terme (PD), Italy; (D.G.); (C.B.)
| | - Carlo Barbera
- Fidia Farmaceutici S.p.A., via Ponte della Fabbrica 3/A, 35031 Abano Terme (PD), Italy; (D.G.); (C.B.)
| | - Nicholas R. Forsyth
- Guy Hilton Research Centre, School of Pharmacy and Bioengineering, Keele University, Thornburrow Drive, Stoke on Trent ST4 7QB, UK;
| | - Nicola Maffulli
- Department of Medicine, Surgery and Dentistry, University of Salerno, Via S. Allende, 84081 Baronissi (SA), Italy; (M.C.C.); (G.D.P.); (N.M.)
- Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, Via San Leonardo 1, 84131 Salerno, Italy
- Centre for Sports and Exercise Medicine, Barts and The London School of Medicine and Dentistry, Mile End Hospital, Queen Mary University of London, 275 Bancroft Road, London E1 4DG, UK
- School of Pharmacy and Bioengineering, Keele University School of Medicine, Thornburrow Drive, Stoke on Trent ST5 5BG, UK
| | - Barbara Barboni
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (V.R.); (A.M.); (M.E.K.); (M.D.M.); (B.B.)
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Veronesi F, Giavaresi G, Bellini D, Casagranda V, Pressato D, Fini M. Evaluation of a new collagen-based medical device (ElastiCo®) for the treatment of acute Achilles tendon injury and prevention of peritendinous adhesions: An in vitro biocompatibility and in vivo investigation. J Tissue Eng Regen Med 2020; 14:1113-1125. [PMID: 32592610 DOI: 10.1002/term.3085] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 05/05/2020] [Accepted: 06/01/2020] [Indexed: 01/05/2023]
Abstract
Tendon healing still represents a challenge for clinicians because it is slow and incomplete. The most injured is the Achilles tendon, and surgery is the therapeutic strategy often adopted because it provides a quicker functional recovery. Peritendinous adhesions are the main complication of surgery with hyperplasia and chemotaxis of fibroblasts. A biomaterial that blocks fibroblast migration, without interfering with the passage of cytokines and growth factors, might be useful. The present study evaluated the biocompatibility of a new Type I collagen-based scaffold (ElastiCo®) and its ability to promote Achilles tendon healing, inhibiting adhesion formation. After verifying in vitro biocompatibility, physical, and mechanical properties of the scaffold, an in vivo study was performed in 28 rats, operated to induce an acute lesion in both Achilles tendons. One tendon was treated with the suture only and the contralateral one with suture wrapped with ElastiCo® film. After 8 and 16 weeks, it was observed that ElastiCo® reduced internal and external peritendinous adhesions and Collagen III content and increased Collagen I. Elastic modulus increased with both treatments over time. Current results highlighted the clinical translationality of ElastiCo® that could improve the quality of life in patients affected by Achilles tendon lesions surgically treated.
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Affiliation(s)
- Francesca Veronesi
- Laboratory of Preclinical and Surgical Studies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Gianluca Giavaresi
- Laboratory of Preclinical and Surgical Studies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | | | | | | | - Milena Fini
- Laboratory of Preclinical and Surgical Studies, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
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Cong S, Sun Y, Lin J, Liu S, Chen J. A Synthetic Graft With Multilayered Co-Electrospinning Nanoscaffolds for Bridging Massive Rotator Cuff Tear in a Rat Model. Am J Sports Med 2020; 48:1826-1836. [PMID: 32453629 DOI: 10.1177/0363546520917684] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Graft bridging is used in massive rotator cuff tear (MRCT); however, the integration of graft-tendon and graft-bone is still a challenge. HYPOTHESIS A co-electrospinning nanoscaffold of polycaprolactone (PCL) with an "enthesis-mimicking" (EM) structure could bridge MRCT, facilitate tendon regeneration, and improve graft-bone healing. STUDY DESIGN Controlled laboratory study. METHODS First, we analyzed the cytocompatibility of the electrospinning nanoscaffolds, including aligned PCL (aPCL), nonaligned PCL (nPCL), aPCL-collagen I, nPCL-collagen II, and nPCL-nanohydroxyapatite (nHA). Second, for the EM condition, nPCL-collagen II and nPCL-nHA were electrospun layer by layer at one end of the aPCL-collagen I; for the control condition, the nPCL was electrospun on the aPCL. In 40 mature male rats, resection of both the supraspinatus and infraspinatus tendons was performed to create MRCT, and the animals were divided randomly into EM and control groups. In both groups, one end of the layered structure was fixed on the footprint of the rotator cuff, whereas the other end of the layered structure was sutured with the tendon stump. The animals were euthanized for harvesting of tissues for histologic and biomechanical analysis at 4 weeks or 8 weeks postoperatively. RESULTS All scaffolds showed good cytocompatibility in vitro. The graft-tendon tissue in the EM group had more regularly arranged cells, denser tissue, a significantly higher tendon maturing score, and more birefringence compared with the control group at 8 weeks after operation. Newly formed fibrocartilage could be observed at the graft-bone interface in both groups by 8 weeks, but the EM group had a higher graft-bone healing score and significantly more newly formed fibrocartilage than the control group. An enthesis-like structure with transitional layers was observed in the EM group at 8 weeks. Biomechanically, the values for maximum failure load and stiffness of the tendon-graft-bone complex were significantly higher in the EM group than in the control group at 8 weeks. CONCLUSION The co-electrospinning nanoscaffold of aPCL-collagen I could be used as a bridging graft to improve early graft-tendon healing for MRCT in a rat model and enhance early enthesis reconstruction in combination with a multilayered structure of nPCL-collagen II and nPCL-nHA. CLINICAL RELEVANCE We constructed a graft to bridge MRCT, enhance graft-tendon healing and graft-bone healing, and reconstruct the enthesis structure.
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Affiliation(s)
- Shuang Cong
- Department of Sports Medicine, Huashan Hospital, Shanghai, China
| | - Yaying Sun
- Department of Sports Medicine, Huashan Hospital, Shanghai, China
| | - Jinrong Lin
- Department of Sports Medicine, Huashan Hospital, Shanghai, China
| | - Shaohua Liu
- Department of Sports Medicine, Huashan Hospital, Shanghai, China
| | - Jiwu Chen
- Department of Sports Medicine, Huashan Hospital, Shanghai, China
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Ge Z, Tang H, Chen W, Wang Y, Yuan C, Tao X, Zhou B, Tang K. Downregulation of type I collagen expression in the Achilles tendon by dexamethasone: a controlled laboratory study. J Orthop Surg Res 2020; 15:70. [PMID: 32093733 PMCID: PMC7038574 DOI: 10.1186/s13018-020-01602-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Accepted: 02/17/2020] [Indexed: 12/16/2022] Open
Abstract
Background Spontaneous Achilles tendon rupture associated with long-term dexamethasone (Dex) use has been reported. However, few studies have investigated the potential mechanism. The aim of this study was to evaluate the effects of oral Dex on type I collagen in humans and rats and its association with tendon rupture. Methods First, six Achilles tendons from patients who received long-term Dex treatment, and another six normal tendons were harvested for histological evaluation. Secondly, 8-week-old rats (n = 72) were randomly assigned to a Dex group or a control group. Type I collagen was studied at the mechanical, histological, and molecular levels after 3 and 5 weeks. Tenocytes isolated from normal human and rat tendon were used to investigate the effect of Dex on cellular scale. Results Histological analysis of human and rat tendon tissue revealed an irregular, disordered arrangement of type I collagen in the Dex group compared with the control group. In addition, In the Dex+ group, type I collagen expression decreased in comparison with the Dex− group in both human and rat tenocytes. The mechanical strength of tendons was significantly reduced in the Dex group (68.87 ± 11.07 N) in comparison with the control group (81.46 ± 7.62 N, P = 0.013) after 5 weeks. Tendons in the Dex group were shorter with smaller cross-sectional areas (10.71 ± 0.34 mm2, 1.44 ± 0.22 mm2, respectively) after 5 weeks than those in the control group (11.13 ± 0.50 mm2, P = 0.050, 2.74 ± 0.34 mm2, P < 0.001, respectively). Conclusions This finding suggests long-term use of Dex that decreases the expression of type I collagen at molecular and tissue levels both in human and rat Achilles tendons. Furthermore, Dex decreases the mechanical strength of the tendon, thereby increasing the risk of Achilles tendon rupture.
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Affiliation(s)
- Zilu Ge
- Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street. 30, Shapingba District, Chongqing, 400038, China
| | - Hong Tang
- Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street. 30, Shapingba District, Chongqing, 400038, China
| | - Wan Chen
- Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street. 30, Shapingba District, Chongqing, 400038, China.
| | - Yunjiao Wang
- Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street. 30, Shapingba District, Chongqing, 400038, China
| | - Chengsong Yuan
- Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street. 30, Shapingba District, Chongqing, 400038, China
| | - Xu Tao
- Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street. 30, Shapingba District, Chongqing, 400038, China
| | - Binghua Zhou
- Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street. 30, Shapingba District, Chongqing, 400038, China
| | - Kanglai Tang
- Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street. 30, Shapingba District, Chongqing, 400038, China
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Sun Y, Kwak JM, Kholinne E, Tan J, Koh KH, Jeon IH. Nonabsorbable Suture Knot on the Tendon Affects Rotator Cuff Healing: A Comparative Study of the Knots on Tendon and Bone in a Rat Model of Rotator Cuff Tear. Am J Sports Med 2019; 47:2809-2815. [PMID: 31412207 DOI: 10.1177/0363546519867928] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Nonabsorbable suture knots are usually used to link the tendon and bone during rotator cuff repair surgery. There are many variations in the arthroscopic knot-tying technique; however, the location of suture knot placement for rotator cuff healing has rarely been studied. HYPOTHESIS The authors compared the rotator cuff healing between knots tied on tendon and bone in a rotator cuff tear rat model. It has been hypothesized that knots can cause chronic inflammation and create the weakest link between tendon and bone, thus affecting rotator cuff healing. STUDY DESIGN Controlled laboratory study. METHODS Bilateral supraspinatus tenotomy and rotator cuff repair at the greater tuberosity were performed on 24 Wistar rats. Nonabsorbable surgical suture knots were made on the right supraspinatus tendon tissue and left humerus inferior to the greater tuberosity, respectively. Twelve rats each were sacrificed at 3 and 9 weeks. Six of the 12 rats were used for biomechanical testing and the remaining 6 for histologic evaluation. RESULTS The surgical knots placed on the bursal side of the tendon migrated to the articular side, as noted on gross observation in 22 of 24 samples. The knots on the tendon group showed significantly inferior tendon-bone integration and significantly inferior biomechanical results in terms of maximum load to failure and stiffness. An obvious chronic foreign body inflammatory reaction was found in the knots on the tendon group at 3 and 9 weeks. Furthermore, inferior bone-tendon interface regeneration and weakest link formation were obtained in the knots on the tendon group compared with those on the bone group. CONCLUSION Nonabsorbable suture knots placed on the tendon migrate to the articular side, causing chronic inflammation and weakening tendon-bone healing, which may explain some retears after rotator cuff repair. CLINICAL RELEVANCE The present animal study suggests that it is not recommended in clinical practice to make several bulky nonabsorbable suture knots on the rotator cuff tendon during rotator cuff repair surgery. It may be better to tie the knots at the bone side or do knotless repair.
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Affiliation(s)
- Yucheng Sun
- Department of Hand Surgery, Affiliated Hospital of Nantong University, College of Medicine, University of Nantong, Nantong, China.,Department of Orthopedic Surgery, ASAN Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea
| | - Jae-Man Kwak
- Department of Orthopedic Surgery, ASAN Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea
| | - Erica Kholinne
- Department of Orthopedic Surgery, ASAN Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.,Department of Orthopedic Surgery, St Carolus Hospital, Jakarta, Indonesia
| | - Jun Tan
- Department of Hand Surgery, Affiliated Hospital of Nantong University, College of Medicine, University of Nantong, Nantong, China
| | - Kyoung-Hwan Koh
- Department of Orthopedic Surgery, ASAN Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea
| | - In-Ho Jeon
- Department of Orthopedic Surgery, ASAN Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea
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Schulz KS, Ash KJ, Cook JL. Clinical outcomes after common calcanean tendon rupture repair in dogs with a loop-suture tenorrhaphy technique and autogenous leukoreduced platelet-rich plasma. Vet Surg 2019; 48:1262-1270. [PMID: 30950083 DOI: 10.1111/vsu.13208] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Revised: 02/22/2019] [Accepted: 03/16/2019] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To report outcomes of dogs with common calcanean tendon (CCT) ruptures treated with a platelet-rich plasma (PRP) enhanced nonabsorbable loop-suture technique. STUDY DESIGN Retrospective case series. ANIMALS Client-owned dogs (n = 12). METHODS Medical records (2015-2017) of dogs with CCT ruptures repaired with a loop-suture tenorrhaphy and autogenous leukoreduced PRP were reviewed for signalment, history, type of injury, treatment, and clinical follow-up. Outcomes were assessed by functional anatomic measurements and Canine Orthopedic Index (COI) scores transformed to percentages, with 100% representing no problems. RESULTS Twelve tendons were treated. Two dogs had major complications that were successfully revised. Follow-up was available in 11 of 12 dogs, with a median time of 12 months (range, 4-36), including COI for 11 dogs and anatomic measurements for 6 dogs. Anatomic measurements did not differ between treated and normal contralateral limbs (midthigh muscle mass P > .99, cranial tibial muscle mass P = .37, CCT diameter P = .08, tibiotarsal joint angle P > .99). Owners scored function (COI) as 96.4% (range, 93.3%-97.8%) and quality of life as 94.6% (range, 92%-98.2%). CONCLUSION Loop-suture tenorrhaphy with application of autogenous leukoreduced PRP at the repair site resulted in restoration of functional anatomic measurements, high COI, and client satisfaction. CLINICAL SIGNIFICANCE Loop-suture tenorrhaphy with local application of autogenous leukoreduced PRP appears to offer an acceptable option to treat CCT injuries in dogs.
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Affiliation(s)
- Kurt S Schulz
- Department of Surgery, Peak Veterinary Referral Center at Ethos, Williston, Vermont
| | - Krisitan J Ash
- Department of Surgery, Peak Veterinary Referral Center at Ethos, Williston, Vermont
| | - James L Cook
- Thompson Laboratory for Regenerative Orthopaedics & Mizzou BioJoint® Center, Missouri Orthopedic Institute, Columbia, Missouri
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Müller SA, Quirk NP, Müller-Lebschi JA, Heisterbach PE, Dürselen L, Majewski M, Evans CH. Response of the Injured Tendon to Growth Factors in the Presence or Absence of the Paratenon. Am J Sports Med 2019; 47:462-467. [PMID: 30550720 DOI: 10.1177/0363546518814534] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND The paratenon is important for Achilles tendon healing. There is much interest in the use of exogenous growth factors (GFs) as potential agents for accelerating the healing of damaged Achilles tendons. PURPOSE/HYPOTHESIS The present study used a rat model to study the responses of the injured Achilles tendon to GFs in the presence or absence of the paratenon. The hypothesis was that responses of the injured tendon to GFs would be lower in the absence of a paratenon. STUDY DESIGN Controlled laboratory study. METHODS A 4-mm defect was created in the right Achilles tendon of 60 skeletally mature rats, which were treated with a validated combination of GFs (bFGF, BMP-12, and TGF-β1). Animals were randomly assigned to the intact paratenon (IP) group or resected paratenon (RP) group. Healing was studied anatomically, mechanically, and histologically after 1, 2, and 4 weeks. RESULTS IP tendons showed improved healing compared with RP tendons. IP tendons were significantly stronger (32.2 N and 48.9 N, respectively) than RP tendons (20.1 N and 31.1 N, respectively) after 1 and 2 weeks. IP tendons did not elongate as much as RP tendons and had greater cross-sectional areas (18.0 mm2, 14.4 mm2, and 16.4 mm2, respectively) after 1, 2, and 4 weeks compared with RP tendons (10.5 mm2, 8.4 mm2, and 11.9 mm2, respectively). On histology, earlier collagen deposition and parallel orientation of fibrils were found for IP tendons. CONCLUSION The paratenon is essential for efficient Achilles tendon healing. Healing with GFs in this Achilles tendon defect model was superior in the presence of the paratenon. CLINICAL RELEVANCE Biological approaches to tendon engineering using GFs are in vogue and have been shown to improve healing of the rat Achilles tendon, most likely by inducing progenitor cells located within the paratenon. Clinically, resection or incision of the paratenon has been proposed for wound closure. Our data demonstrate the fundamental importance of the paratenon, which therefore should be preserved during Achilles tendon repair, especially if augmented with products such as platelet-rich plasma or autologous conditioned serum that are rich in GFs.
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Affiliation(s)
- Sebastian A Müller
- Department of Orthopedic Surgery, University of Basel, Basel, Switzerland.,Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Nicholas P Quirk
- Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | - Lutz Dürselen
- Institute of Orthopedic Research and Biomechanics, University of Ulm, Ulm, Germany
| | - Martin Majewski
- Department of Orthopedic Surgery, University of Basel, Basel, Switzerland
| | - Christopher H Evans
- Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, Minnesota, USA
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Effects of freeze-thaw on the biomechanical and structural properties of the rat Achilles tendon. J Biomech 2018; 81:52-57. [DOI: 10.1016/j.jbiomech.2018.09.012] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2018] [Revised: 09/10/2018] [Accepted: 09/11/2018] [Indexed: 11/17/2022]
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Cai J, Yang Y, Ai C, Jin W, Sheng D, Chen J, Chen S. Bone Marrow Stem Cells-Seeded Polyethylene Terephthalate Scaffold in Repair and Regeneration of Rabbit Achilles Tendon. Artif Organs 2018; 42:1086-1094. [PMID: 30294929 DOI: 10.1111/aor.13298] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Revised: 05/11/2018] [Accepted: 05/25/2018] [Indexed: 12/16/2022]
Abstract
The objective of this study was to evaluate the effect of bone marrow stem cells (BMSCs)-seeded polyethylene terephthalate (PET) scaffold for Achilles tendon repair in a rabbit model. The allogeneic BMSCs were seeded onto the PET scaffold and cultured in vitro for 14 days. Sixteen mature New Zealand rabbits underwent surgery to establish a 2-cm Achilles tendon defect model. The BMSCs-seeded PET scaffold was implanted into the defect of one limb (BMSCs-PET group), while the PET scaffold without BMSCs was implanted into the defect of contralateral limb as the control (PET group). All rabbits were sacrificed at 6 and 12 weeks after surgery. At 12 weeks after surgery, macroscopic and histological results showed formation of tendon-like tissues, and the structure was more mature in the BMSCs-PET group. Immunohistochemical analysis and real-time polymerase chain reaction (RT-PCR) demonstrated that the collagen I and collagen III were significantly higher in the BMSCs-PET group compared with those in the PET group. Mechanically, both the failure load and the average stiffness were significantly higher in the BMSCs-PET group than those in the PET group. In conclusion, BMSCs-seeded PET scaffold could effectively facilitate the healing process after being implanted in a rabbit Achilles tendon defect model.
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Affiliation(s)
- Jiangyu Cai
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, P.R. China
| | - Yimeng Yang
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, P.R. China
| | - Chengchong Ai
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, P.R. China
| | - Wenhe Jin
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, P.R. China
| | - Dandan Sheng
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, P.R. China
| | - Jun Chen
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, P.R. China
| | - Shiyi Chen
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, P.R. China
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Ohashi Y, Nakase J, Shimozaki K, Torigoe K, Tsuchiya H. Evaluation of dynamic change in regenerated tendons in a mouse model. J Exp Orthop 2018; 5:37. [PMID: 30242576 PMCID: PMC6150864 DOI: 10.1186/s40634-018-0152-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Accepted: 09/13/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Using the film model method, the process whereby a substance called tendon gel is secreted from transected tendon ends and changed into a tendon after application of a traction force is known. The objective of this study was to investigate the association between mechanical properties in the early stages of tendon regeneration and time by using the film model method. METHOD Adult male ddY mice, closed colony mice established and maintained in Japan, were prepared for each experimental group. The study animals were 30 mice and were divided into three groups of 10 mice each. Ten specimens of tendon gel secreted from the transected tendon ends were collected on days 10, 15, and 20 postoperatively. While a traction force of 0.00245 N was applied to these specimens, the process of tendon gel changing into a tendon was video recorded for 24 h, and the length of extension was measured over time. Regenerated tendons were stained with hematoxylin and eosin for histological examination. Healing site was studied histologically according to the our maturity score with reference to the Bonar's scale. RESULTS The day 10 specimens gradually stretched for 12 h after the start of pulling and transformed into tendons. In contrast, the day 15 and 20 specimens stretched immediately after the start of pulling and transformed into tendons. The day 10 specimens stretched significantly more than the day 15 and 20 specimens (mechanical strain; 0.43 ± 0.26%, 0.03 ± 0.02%, and 0.03 ± 0.01%, respectively)Statistically significant differences were observed in the day 10 specimens than in the day 15 and 20 specimens. (P < 0.017). Using our maturity scores, the day 15 and 20 specimens were more mature than the day 10 specimens. (1.6 ± 0.68, 3.9 ± 0.54, and 4.8 ± 0.64, respectively) Statistically significant differences were observed in the day 10 specimens than in the day 15 and 20 specimens (P < 0.017). CONCLUSION Tendon gel physiologically and histologically matures on or after day 15 and becomes stronger dynamically in mechanical strength after day 15 than after day 10.
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Affiliation(s)
- Yoshinori Ohashi
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Junsuke Nakase
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
| | - Kengo Shimozaki
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Kojun Torigoe
- Department of Rehabilitation, Fukui Health Science University Faculty of Health Science, Fukui, Japan
| | - Hiroyuki Tsuchiya
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
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Zhang B, Luo Q, Deng B, Morita Y, Ju Y, Song G. Construction of tendon replacement tissue based on collagen sponge and mesenchymal stem cells by coupled mechano-chemical induction and evaluation of its tendon repair abilities. Acta Biomater 2018; 74:247-259. [PMID: 29702290 DOI: 10.1016/j.actbio.2018.04.047] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Revised: 04/23/2018] [Accepted: 04/23/2018] [Indexed: 12/29/2022]
Abstract
Tissue engineering is an ideal therapeutic strategy for the development of functional tendon replacement tissue for tendon repair in the clinic. Currently, the synergistic roles of mechano-chemical factors and the mechanisms involved in tendon repair and regeneration are not fully understood. In this study, we developed a three-dimensional (3D) culture system based on a silicone chamber and collagen sponge scaffold that can deliver cyclic mechanical stretch and biochemical stimulation to bone marrow-derived mesenchymal stem cells (BMSCs) seeded on the scaffold. We found that the combined stimulation of cyclic stretch and transforming growth factor beta 1 (TGF-β1) treatment not only increased cell viability but also synergistically promoted the differentiation of BMSCs into tenocytes in a 3D culture environment. Meanwhile, the combined stimulation increased the Young's modulus of the BMSC-collagen sponge constructs by reducing the porosity of the scaffold compared to the non-treated constructs. Furthermore, a rat Achilles tendon in situ repair experiment showed that enhanced tendon regeneration was achieved using the BMSC-collagen sponge construct combined with cyclic stretch and TGF-β1, as confirmed by Achilles functional index (AFI) measurement, morphological observation, histological analysis, and mechanical testing. These results suggest that this approach could offer a practical benefit in tendon healing and future tendon tissue engineering. STATEMENT OF SIGNIFICANCE This study aims to disclose the crucial roles of the coupled induction by mechano-chemical stimulation in tendon tissue engineering and clarifies their collaborative control mechanisms. We developed a three-dimensional (3D) culture system based on a silicone chamber and collagen sponge scaffold that could deliver cyclic mechanical stretch and biochemical stimulation to bone marrow-derived mesenchymal stem cells (BMSCs). We found that the combined stimulation of cyclic stretch and transforming growth factor beta 1 (TGF-β1) could result in an improvement of tissue-engineered construct for enhancing tendon healing. These results suggest that this approach could offer a practical benefit in tendon healing and future tendon tissue engineering.
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Affiliation(s)
- Bingyu Zhang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China; Post-Doctoral Mobile Stations of Biology, Chongqing University, Chongqing 400030, China
| | - Qing Luo
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China.
| | - Bin Deng
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China
| | - Yasuyuki Morita
- Department of Mechanical Science & Engineering, Graduate School of Engineering, Nagoya University, Nagoya 464-8603, Japan
| | - Yang Ju
- Department of Mechanical Science & Engineering, Graduate School of Engineering, Nagoya University, Nagoya 464-8603, Japan
| | - Guanbin Song
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China.
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Biomaterials in Tendon and Skeletal Muscle Tissue Engineering: Current Trends and Challenges. MATERIALS 2018; 11:ma11071116. [PMID: 29966303 PMCID: PMC6073924 DOI: 10.3390/ma11071116] [Citation(s) in RCA: 90] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 06/20/2018] [Accepted: 06/25/2018] [Indexed: 12/17/2022]
Abstract
Tissue engineering is a promising approach to repair tendon and muscle when natural healing fails. Biohybrid constructs obtained after cells’ seeding and culture in dedicated scaffolds have indeed been considered as relevant tools for mimicking native tissue, leading to a better integration in vivo. They can also be employed to perform advanced in vitro studies to model the cell differentiation or regeneration processes. In this review, we report and analyze the different solutions proposed in literature, for the reconstruction of tendon, muscle, and the myotendinous junction. They classically rely on the three pillars of tissue engineering, i.e., cells, biomaterials and environment (both chemical and physical stimuli). We have chosen to present biomimetic or bioinspired strategies based on understanding of the native tissue structure/functions/properties of the tissue of interest. For each tissue, we sorted the relevant publications according to an increasing degree of complexity in the materials’ shape or manufacture. We present their biological and mechanical performances, observed in vitro and in vivo when available. Although there is no consensus for a gold standard technique to reconstruct these musculo-skeletal tissues, the reader can find different ways to progress in the field and to understand the recent history in the choice of materials, from collagen to polymer-based matrices.
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Müller SA, Evans CH, Heisterbach PE, Majewski M. The Role of the Paratenon in Achilles Tendon Healing: A Study in Rats. Am J Sports Med 2018; 46:1214-1219. [PMID: 29505741 DOI: 10.1177/0363546518756093] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND The role of the paratenon in tendon healing is unknown. The present study compares healing in the presence or absence of the paratenon in an Achilles tendon defect model in rats. HYPOTHESIS Resection of the paratenon impairs tendon healing. STUDY DESIGN Controlled laboratory study. METHODS Sixty skeletally mature Sprague Dawley rats were randomly assigned to either a resected paratenon (RP) group or an intact paratenon (IP) group. In all animals, a 4-mm portion of the Achilles tendon was resected in the midsubstance. In the RP group, the paratenon was resected completely. In the IP group, the paratenon was opened longitudinally and closed again after the tendon defect had been created. One, 2, and 4 weeks after surgery, 7 animals per group were tested biomechanically and 3 animals per group examined histologically. RESULTS The recovery of mechanical strength was much more rapid in IP tendons. Tear resistance was significantly increased for IP tendons (41.3 ± 8.8 N and 47.3 ± 14.1 N, respectively) compared with RP tendons (19.3 ± 9.1 N and 33.2 ± 6.4 N, respectively) after 1 and 2 weeks. The cross-sectional area was larger in the IP group after 1 and 2 weeks (8.2 ± 2.3 mm2 and 11.3 ± 3.1 mm2 vs 5.0 ± 2.4 mm2 and 5.9 ± 2.0 mm2, respectively) compared with the RP group. Tendon stiffness was greater in the IP group after 1 week (10.4 ± 1.9 N/mm vs 4.5 ± 1.6 N/mm, respectively) compared with the RP group. In comparison, normal contralateral tendons had a maximal tear resistance of 56.6 ± 7.2 N, a cross-sectional area of 3.6 ± 0.7 mm2, and stiffness of 17.3 ± 3.8 N/mm. Hematoxylin and eosin staining revealed slightly delayed healing of RP tendons. Early collagen formation was seen in the IP group already after 1 week, whereas in the RP group, this only occurred after 2 weeks. After 4 weeks, the IP tendons showed more collagen crimp formation than the RP tendons. CONCLUSION An intact paratenon promotes healing of the Achilles tendon. CLINICAL RELEVANCE Although incision or resection of the paratenon has been advocated when repairing injured or degenerative tendons, our data suggest that the integrity of the paratenon should be preserved.
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Affiliation(s)
- Sebastian A Müller
- Department of Orthopedic Surgery, University of Basel, Basel, Switzerland.,Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Christopher H Evans
- Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Martin Majewski
- Department of Orthopedic Surgery, University of Basel, Basel, Switzerland
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Abstract
Tendons connect muscles to bones, ensuring joint movement. With advanced age, tendons become more prone to degeneration followed by injuries. Tendon repair often requires lengthy periods of rehabilitation, especially in elderly patients. Existing medical and surgical treatments often fail to regain full tendon function. The development of novel treatment methods has been hampered due to limited understanding of basic tendon biology. Recently, it was discovered that tendons, similar to other mesenchymal tissues, contain tendon stem/progenitor cells (TSPCs) which possess the common stem cell properties. The current strategies for enhancing tendon repair consist mainly of applying stem cells, growth factors, natural and artificial biomaterials alone or in combination. In this review, we summarise the basic biology of tendon tissues and provide an update on the latest repair proposals for tendon tears. Cite this article: EFORT Open Rev 2017;2:332-342. DOI: 10.1302/2058-5241.2.160075
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Affiliation(s)
- Fan Wu
- Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig-Maximilians-University (LMU), Munich, Germany
| | - Michael Nerlich
- Department of Trauma Surgery, University Regensburg Medical Center, Regensburg, Germany
| | - Denitsa Docheva
- Experimental Trauma Surgery, Department of Trauma Surgery, University Regensburg Medical Center, Regensburg, Germany and Department of Medical Biology, Medical University-Plovdiv, Plovdiv, Bulgaria
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Zheng Z, Ran J, Chen W, Hu Y, Zhu T, Chen X, Yin Z, Heng BC, Feng G, Le H, Tang C, Huang J, Chen Y, Zhou Y, Dominique P, Shen W, Ouyang HW. Alignment of collagen fiber in knitted silk scaffold for functional massive rotator cuff repair. Acta Biomater 2017; 51:317-329. [PMID: 28093363 DOI: 10.1016/j.actbio.2017.01.041] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Revised: 01/11/2017] [Accepted: 01/12/2017] [Indexed: 12/31/2022]
Abstract
Rotator cuff tear is one of the most common types of shoulder injuries, often resulting in pain and physical debilitation. Allogeneic tendon-derived decellularized matrices do not have appropriate pore size and porosity to facilitate cell infiltration, while commercially-available synthetic scaffolds are often inadequate at inducing tenogenic differentiation. The aim of this study is to develop an advanced 3D aligned collagen/silk scaffold (ACS) and investigate its efficacy in a rabbit massive rotator cuff tear model. ACS has similar 3D alignment of collagen fibers as natural tendon with superior mechanical characteristics. Based on ectopic transplantation studies, the optimal collagen concentration (10mg/ml), pore diameter (108.43±7.25μm) and porosity (97.94±0.08%) required for sustaining a stable macro-structure conducive for cellular infiltration was determined. Within in vitro culture, tendon stem/progenitor cells (TSPCs) displayed spindle-shaped morphology, and were well-aligned on ACS as early as 24h. TSPCs formed intercellular contacts and deposited extracellular matrix after 7days. With the in vivo rotator cuff repair model, the regenerative tendon of the ACS group displayed more conspicuous native microstructures with larger diameter collagen fibrils (48.72±3.75 vs. 44.26±5.03nm) that had better alignment and mechanical properties (139.85±49.36vs. 99.09±33.98N) at 12weeks post-implantation. In conclusion, these findings demonstrate the positive efficacy of the macroporous 3D aligned scaffold in facilitating rotator cuff tendon regeneration, and its practical applications for rotator cuff tendon tissue engineering. STATEMENT OF SIGNIFICANCE Massive rotator cuff tear is one of the most common shoulder injuries, and poses a formidable clinical challenge to the orthopedic surgeon. Tissue engineering of tendon can potentially overcome the problem. However, more efficacious scaffolds with good biocompatibility, appropriate pore size, favorable inductivity and sufficient mechanical strength for repairing massive rotator cuff tendon injuries need to be developed. In this study, we developed a novel macroporous 3D aligned collagen/silk scaffold, and demonstrated that this novel scaffold enhanced the efficacy of rotator cuff tendon regeneration by inducing aligned supracellular structures similar to natural tendon, which in turn enhanced cellular infiltration and tenogenic differentiation of stem/progenitor cells from both the tendon itself and surrounding tissues. Hence, it can potentially be a clinically useful application for tendon tissue engineering.
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