Chen Can, Chen Yang, Li Muzh, Xiao Han, Shi Qiang, Zhang Tao, Li Xing, Zhao Chunfeng, Hu Jianzhong, Lu Hongbin
Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Research Centre of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculeskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China.
Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Research Centre of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculeskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China.
Biomaterials. 2020 Aug;250:119996. doi: 10.1016/j.biomaterials.2020.119996. Epub 2020 Apr 17.
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 CXCR4SMSCs injection (C-SDF-1α/BDFM + CXCR4SMSCs), BDFM in-vitro pre-loaded CXCR4SMSCs (BDFM/CXCR4SMSCs), or direct suture only (CTL). At postoperative 14-day, compared with BDFM/CXCR4SMSCs, C-SDF-1α/BDFM + CXCR4SMSCs showed a little more CXCR4SMSCs at the healing site. At postoperative week 4 or 8, rats treated with C-SDF-1α/BDFM + CXCR4SMSCs presented a similar RC healing quality as BDFM/CXCR4SMSCs, both of which were significantly better than the CTL. Collectively, compared with conventional BDFM/CXCR4SMSCs, C-SDF-1α/BDFM, as a cell-free graft with chemotaxis, could recruit postoperative injected CXCR4cells 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.
肩袖撕裂（RCT）后快速且功能性的肌腱附着点再生在临床上仍然是一项挑战。目前用于解决这一挑战的组织工程策略主要集中在开发在支架上体外接种细胞的移植物。然而，这种方式复杂且耗时，此外，这种移植物在细胞培养箱外保存非常不便，因此限制了它们的临床应用。开发一种具有趋化作用以募集术后注射细胞的无细胞移植物可能是解决这些问题的一种有前景的方法。在此，我们制备了一种能够结合胶原蛋白并具有趋化作用的重组SDF-1α（称为C-SDF-1α），然后将其 tethered 在书本状脱细胞纤维软骨基质（BDFM）的胶原纤维上以制造这种无细胞移植物（C-SDF-1α/BDFM）。这种C-SDF-1α/BDFM无细胞毒性且免疫原性低，允许滑膜来源的间充质干细胞（SMSCs）附着和增殖，并显示出优异的软骨生成诱导能力。更重要的是，C-SDF-1α/BDFM在体外和体内以缓释方式释放 tethered 的SDF-1α，从而稳定地募集趋化因子（C-X-C基序）受体4阳性（CXCR4）细胞。RCT大鼠用C-SDF-1α/BDFM联合术后注射CXCR4SMSCs（C-SDF-1α/BDFM + CXCR4SMSCs）、BDFM体外预加载CXCR4SMSCs（BDFM/CXCR4SMSCs）或仅直接缝合（CTL）进行急性修复。术后14天时，与BDFM/CXCR4SMSCs相比，C-SDF-1α/BDFM + CXCR4SMSCs在愈合部位的CXCR4SMSCs略多。术后第4周或第8周，用C-SDF-1α/BDFM + CXCR4SMSCs治疗的大鼠的肩袖愈合质量与BDFM/CXCR4SMSCs相似，两者均明显优于CTL。总体而言，与传统的BDFM/CXCR4SMSCs相比，C-SDF-1α/BDFM作为一种具有趋化作用的无细胞移植物，可以将术后注射的CXCR4细胞募集到愈合部位参与肩袖愈合，从而避免了在支架上体外接种细胞的复杂过程以及对细胞培养箱外移植物的极大护理需求，使其在临床应用中非常方便。
