Functional decellularized fibrocartilaginous matrix graft for rotator cuff enthesis regeneration: A novel technique to avoid in-vitro loading of cells

Chen, Can; Chen, Yang; Li, Muzh; Xiao, Han; Shi, Qiang; Zhang, Tao; Li, Xing; Zhao, Chunfeng; Hu, Jianzhong; Lu, Hongbin

doi:10.1016/j.biomaterials.2020.119996

Cited by 45 publications

(44 citation statements)

References 62 publications

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“…[43] Recently, tissue engineering was prevalent for repairing enthesis injury and showed promising results of fibrocartilage and bone regeneration, associated with better mechanical testing results. [8,44,45] In the present studies, we found that better regeneration of fibrocartilage was higly correlated with the number of Prx1 + cells and was accompanied by better mechanical testing results, which was consistent with previous reports.These data suggested that the fibrocartilage regeneration directly influenced the enthesis healing quality and could be a reliable indicator for the enthesis regeneration.…”

Section: Discussionsupporting

confidence: 93%

Mechanical stimulation promotes enthesis injury repair by mobilizing Prx1⁺cells via ciliary TGF-β signaling

Xiao

Zhang

et al. 2021

Preprint

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Proper mechanical stimulation can improve rotator cuff enthsis injury repair. However, the underlying mechanism of mechanical stimulation promoting injury repair is still unknown. In this study, we found that Prx1+ cell was essential for murine rotator cuff enthesis development identified by single-cell RNA sequence and involved in the injury repair. Proper mechanical stimulation could promote the migration of Prx1+ cells to enhance enthesis injury repair. Meantime, TGF-β signaling and primary cilia played an essential role in mediating mechanical stimulation signaling transmission. Proper mechanical stimulation enhanced the release of active TGF-β1 to promote migration of Prx1+ cells. Inhibition of TGF-β signaling eliminated the stimulatory effect of mechanical stimulation on Prx1+ cell migration and enthesis injury repair. In addition, knockdown of Pallidin to inhibit TGF-βR2 translocation to the primary cilia or deletion of IFT88 in Prx1+ cells also restrained the mechanics-induced Prx1+ cells migration. These findings suggested that mechanical stimulation could increase the release of active TGF-β1 and enhance the mobilization of Prx1+ cells to promote enthesis injury repair via ciliary TGF-β signaling.

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Section: Discussionsupporting

confidence: 93%

Mechanical stimulation promotes enthesis injury repair by mobilizing Prx1⁺cells via ciliary TGF-β signaling

Xiao

Zhang

et al. 2021

Preprint

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“…Rabbit synovial fluid MSCs were directly injected or encapsulated in an injectable hydrogel to repair cartilage defects, but few studies have reported the application of SMSCs in cartilage repair, especially endogenous SMSCs. Compared with other study, where postoperative intra-articular injected SMSCs were recruited by SDF-1α (stromal cell-derived factor-1 alpha)–binding decellularized fibrocartilage matrix to repair rotator cuff ( 63 ), we used a stem cell–homing peptide to recruit the endogenous SMSCs and stimulate regenerative process in cartilage, reducing the risk of using exogenous cells. We speculate that the BMHP SKP contributed to the migration of SMSCs and/or the homing of SMSCs near the cartilage surface.…”

Section: Discussionmentioning

confidence: 99%

Stem cell–homing hydrogel-based miR-29b-5p delivery promotes cartilage regeneration by suppressing senescence in an osteoarthritis rat model

et al. 2022

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Osteoarthritis (OA) is a common joint disease characterized by progressive loss of cartilage and reduction in lubricating synovial fluid, which lacks effective treatments currently. Here, we propose a hydrogel-based miRNA delivery strategy to rejuvenate impaired cartilage by creating a regenerative microenvironment to mitigate chondrocyte senescence that mainly contributes to cartilage breakdown during OA development. An aging-related miRNA, miR-29b-5p, was first found to be markedly down-regulated in OA cartilage, and their up-regulation suppressed the expression of matrix metalloproteinases and senescence-associated genes ( P16 INK4a /P21 ) via ten-eleven-translocation enzyme 1 (TET1). An injectable bioactive self-assembling peptide nanofiber hydrogel was applied to deliver agomir-29b-5p, which was functionalized by conjugating a stem cell–homing peptide SKPPGTSS for endogenous synovial stem cell recruitment simultaneously. Sustained miR-29b-5p delivery and recruitment of synovial stem cells and their subsequent differentiation into chondrocytes led to successful cartilage repair and chondrocyte rejuvenation. This strategy enables miRNA-based therapeutic modality to become a viable alternative for surgery in OA treatment.

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“…The CBD used in this study originated from the A3 domain of vWF that binds to collagen. 1,14,54 Chen et al 8 recently fused this CBD into stromal cell-derived factor 1a (SDF-1a) to synthesize a recombinant SDF-1a, which not only preserved the chemotactic function of SDF-1a but could also bind to collagen. In this study, we fused this CBD into the N-terminus of BMP-12 to synthesize a recombinant BMP-12.…”

Section: Discussionmentioning

confidence: 99%

Cell-Free Book-Shaped Decellularized Tendon Matrix Graft Capable of Controlled Release of BMP-12 to Improve Tendon Healing in a Rat Model

Xiao

Chen

et al. 2021

Am J Sports Med

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Background: Achilles tendon (AT) defects often occur in traumatic and chronic injuries. Currently, no graft can satisfactorily regenerate parallel tendinous tissue at the defect site to completely restore AT function. Purpose: To develop a cell-free functional graft by tethering bone morphogenetic protein 12 (BMP-12) on a book-shaped decellularized tendon matrix (BDTM) and to determine whether this graft is more beneficial for AT defect healing than an autograft. Study Design: Controlled laboratory study. Methods: Canine patellar tendon was sectioned into a book shape and decellularized to fabricate a BDTM. The collagen-binding domain (CBD) was fused into the N-terminus of BMP-12 to synthesize a recombinant BMP-12 (CBD-BMP-12), which was tethered to the BDTM to prepare a cell-free functional graft (CBD-BMP-12/BDTM). After its tensile resistance, tenogenic inducibility, and BMP-12 release dynamics were evaluated, the efficacy of the graft for tendon regeneration was determined in a rat model. A total of 140 mature male Sprague-Dawley rats underwent AT tenotomy. The defect was reconstructed with reversed AT (autograft group), native BMP-12 tethered to an intact decellularized tendon matrix (IDTM; NAT-BMP-12/IDTM group), native BMP-12 tethered to a BDTM (NAT-BMP-12/BDTM group), CBD-BMP-12 tethered on an IDTM (CBD-BMP-12/IDTM group), and CBD-BMP-12 tethered on a BDTM (CBD-BMP-12/BDTM group). The rats were sacrificed 4 or 8 weeks after surgery to harvest AT specimens. Six specimens from each group at each time point were used for histological evaluation; the remaining 8 specimens were used for biomechanical testing. Results: In vitro CBD-BMP-12/BDTM was noncytotoxic, showed high biomimetics with native tendons, was suitable for cell adhesion and growth, and had superior tenogenic inducibility. In vivo the defective AT in the CBD-BMP-12/BDTM group regenerated more naturally than in the other groups, as indicated by more spindle-shaped fibroblasts embedded in a matrix of parallel fibers. The biomechanical properties of the regenerated AT in the CBD-BMP-12/BDTM group also increased more significantly than in the other groups. Conclusion: CBD-BMP-12/BDTM is more beneficial than autograft for healing AT defects in a rat model. Clinical Relevance: The findings of this study demonstrate that CBD-BMP-12/BDTM can serve as a practical graft for reconstructing AT defects.

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Functional decellularized fibrocartilaginous matrix graft for rotator cuff enthesis regeneration: A novel technique to avoid in-vitro loading of cells

Cited by 45 publications

References 62 publications

Mechanical stimulation promotes enthesis injury repair by mobilizing Prx1⁺cells via ciliary TGF-β signaling

Mechanical stimulation promotes enthesis injury repair by mobilizing Prx1⁺cells via ciliary TGF-β signaling

Stem cell–homing hydrogel-based miR-29b-5p delivery promotes cartilage regeneration by suppressing senescence in an osteoarthritis rat model

Cell-Free Book-Shaped Decellularized Tendon Matrix Graft Capable of Controlled Release of BMP-12 to Improve Tendon Healing in a Rat Model

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Functional decellularized fibrocartilaginous matrix graft for rotator cuff enthesis regeneration: A novel technique to avoid in-vitro loading of cells

Cited by 45 publications

References 62 publications

Mechanical stimulation promotes enthesis injury repair by mobilizing Prx1+cells via ciliary TGF-β signaling

Mechanical stimulation promotes enthesis injury repair by mobilizing Prx1+cells via ciliary TGF-β signaling

Stem cell–homing hydrogel-based miR-29b-5p delivery promotes cartilage regeneration by suppressing senescence in an osteoarthritis rat model

Cell-Free Book-Shaped Decellularized Tendon Matrix Graft Capable of Controlled Release of BMP-12 to Improve Tendon Healing in a Rat Model

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Mechanical stimulation promotes enthesis injury repair by mobilizing Prx1⁺cells via ciliary TGF-β signaling

Mechanical stimulation promotes enthesis injury repair by mobilizing Prx1⁺cells via ciliary TGF-β signaling