TY - JOUR
T1 - Functional decellularized fibrocartilaginous matrix graft for rotator cuff enthesis regeneration
T2 - A novel technique to avoid in-vitro loading of cells
AU - Chen, Can
AU - Chen, Yang
AU - Li, Muzh
AU - Xiao, Han
AU - Shi, Qiang
AU - Zhang, Tao
AU - Li, Xing
AU - Zhao, Chunfeng
AU - Hu, Jianzhong
AU - Lu, Hongbin
N1 - Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/8
Y1 - 2020/8
N2 - Rapid and functional enthesis regeneration after rotator cuff tear (RCT) remains a challenge in clinic. Current tissue-engineering strategies for solving this challenge are focused on developing grafts with the mode of in-vitro loading cells on a scaffold. However, this mode is complicated and time-inefficient, moreover the preservation of this graft outside a cell incubator is highly inconvenient, thus limiting their clinical application. Developing a cell-free graft with chemotaxis to recruit postoperative injected cells may be a promising approach to solve these problems. Herein, we prepared a recombinant SDF-1α (termed as C-SDF-1α) capable of binding collagen and chemotaxis, which were then tethered on the collagen fibers of book-shaped decellularized fibrocartilage matrix (BDFM) to fabricate this cell-free graft (C-SDF-1α/BDFM). This C-SDF-1α/BDFM is noncytotoxicity and low-immunogenicity, allows synovium-derived mesenchymal stem cells (SMSCs) attachment and proliferation, and shows superior chondrogenic inducibility. More importantly, C-SDF-1α/BDFM released the tethered SDF-1α with a sustained release profile in-vitro and in-vivo, thus steadily recruiting chemokine (C-X-C motif) receptor 4 positive (CXCR4+) cells. Rats with RCT were repaired acutely with C-SDF-1α/BDFM together with postoperative CXCR4+SMSCs injection (C-SDF-1α/BDFM + CXCR4+SMSCs), BDFM in-vitro pre-loaded CXCR4+SMSCs (BDFM/CXCR4+SMSCs), or direct suture only (CTL). At postoperative 14-day, compared with BDFM/CXCR4+SMSCs, C-SDF-1α/BDFM + CXCR4+SMSCs showed a little more CXCR4+SMSCs at the healing site. At postoperative week 4 or 8, rats treated with C-SDF-1α/BDFM + CXCR4+SMSCs presented a similar RC healing quality as BDFM/CXCR4+SMSCs, both of which were significantly better than the CTL. Collectively, compared with conventional BDFM/CXCR4+SMSCs, C-SDF-1α/BDFM, as a cell-free graft with chemotaxis, could recruit postoperative injected CXCR4+cells into the healing site to participating RC healing, thus avoiding the complex process of in-vitro loading cells on a scaffold and necessitating immense care for the graft outside cell incubator, making it very convenient for clinical application.
AB - Rapid and functional enthesis regeneration after rotator cuff tear (RCT) remains a challenge in clinic. Current tissue-engineering strategies for solving this challenge are focused on developing grafts with the mode of in-vitro loading cells on a scaffold. However, this mode is complicated and time-inefficient, moreover the preservation of this graft outside a cell incubator is highly inconvenient, thus limiting their clinical application. Developing a cell-free graft with chemotaxis to recruit postoperative injected cells may be a promising approach to solve these problems. Herein, we prepared a recombinant SDF-1α (termed as C-SDF-1α) capable of binding collagen and chemotaxis, which were then tethered on the collagen fibers of book-shaped decellularized fibrocartilage matrix (BDFM) to fabricate this cell-free graft (C-SDF-1α/BDFM). This C-SDF-1α/BDFM is noncytotoxicity and low-immunogenicity, allows synovium-derived mesenchymal stem cells (SMSCs) attachment and proliferation, and shows superior chondrogenic inducibility. More importantly, C-SDF-1α/BDFM released the tethered SDF-1α with a sustained release profile in-vitro and in-vivo, thus steadily recruiting chemokine (C-X-C motif) receptor 4 positive (CXCR4+) cells. Rats with RCT were repaired acutely with C-SDF-1α/BDFM together with postoperative CXCR4+SMSCs injection (C-SDF-1α/BDFM + CXCR4+SMSCs), BDFM in-vitro pre-loaded CXCR4+SMSCs (BDFM/CXCR4+SMSCs), or direct suture only (CTL). At postoperative 14-day, compared with BDFM/CXCR4+SMSCs, C-SDF-1α/BDFM + CXCR4+SMSCs showed a little more CXCR4+SMSCs at the healing site. At postoperative week 4 or 8, rats treated with C-SDF-1α/BDFM + CXCR4+SMSCs presented a similar RC healing quality as BDFM/CXCR4+SMSCs, both of which were significantly better than the CTL. Collectively, compared with conventional BDFM/CXCR4+SMSCs, C-SDF-1α/BDFM, as a cell-free graft with chemotaxis, could recruit postoperative injected CXCR4+cells into the healing site to participating RC healing, thus avoiding the complex process of in-vitro loading cells on a scaffold and necessitating immense care for the graft outside cell incubator, making it very convenient for clinical application.
KW - Collagen-affinity peptide
KW - Decellularized matrix
KW - Enthesis regeneration
KW - Rotator cuff
KW - SDF-1α
KW - Seeding-cells loading
UR - http://www.scopus.com/inward/record.url?scp=85083464407&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083464407&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2020.119996
DO - 10.1016/j.biomaterials.2020.119996
M3 - Article
C2 - 32334201
AN - SCOPUS:85083464407
SN - 0142-9612
VL - 250
JO - Biomaterials
JF - Biomaterials
M1 - 119996
ER -