Controlled release of collagen-binding SDF-1α from the collagen scaffold promoted tendon regeneration in a rat Achilles tendon defect model

• Published in: Biomaterials 2018-04, Vol.162, p.22-33
• Main Authors: Sun, Jie, Mou, Chenchen, Shi, Qin, Chen, Bing, Hou, Xianglin, Zhang, Wen, Li, Xiaoran, Zhuang, Yan, Shi, Jiajia, Chen, Yanyan, Dai, Jianwu
• Format: Article
• Language: English
• Subjects: Achilles Tendon - cytology; Achilles Tendon - metabolism; Animals; Cell Movement - physiology; Cells, Cultured; Chemokine CXCL12 - chemistry; Chemokine CXCL12 - metabolism; Collagen scaffold; Controlled release; Immunohistochemistry; In situ regeneration; Male; Mesenchymal Stromal Cells - metabolism; Mesenchymal Stromal Cells - ultrastructure; Microscopy, Electron, Transmission; Rats; Rats, Sprague-Dawley; Receptors, CXCR4 - metabolism; SDF-1α; Tenascin - metabolism; Tendon regeneration; Tissue Scaffolds - chemistry
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2018.02.008

It had been demonstrated that stromal cell-derived factor-1α (SDF-1α) could promote in situ tendon regeneration by recruiting endogenous cells. However, native SDF-1α diffuses too fast in vivo, reducing its local concentration and efficacy. In this study, we prepared a recombinant SDF-1α containing a collagen-binding domain (CBD-SDF-1α) and developed a functional collagen scaffold by tethering CBD-SDF-1α on the collagen scaffold for in situ tendon regeneration. CBD-SDF-1α could induce the migration of mesenchymal stem cells, dermal fibroblasts and Achilles tendon fibroblasts in vitro, and achieve controlled release from the collagen scaffold. In a rat Achilles tendon defect model, the functional scaffold could increase the recruitment of CXCR4 positive fibroblast-like cells and the deposition of Tenascin-C at 7 days after implantation. After 4 and 12 weeks, the functional collagen scaffold could promote the expression of type I collagen, increase the diameters of collagen fibrils and improve the mechanical properties of regenerated tendons. Hence, the functional scaffold increased the efficacy of tendon regeneration by controlling release of SDF-1α, enhancing the recruitment of fibroblast-like cells and providing instructive microenvironment and mechanical support for tendon regeneration. Therefore, CBD-SDF-1α-modified collagen scaffold could serve as a practical application for tendon regeneration.