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

It had been demonstrated that stromal cell-derived factor-1 alpha (SDF-1 alpha) could promote in situ tendon regeneration by recruiting endogenous cells. However, native SDF-1 alpha diffuses too fast in vivo, reducing its local concentration and efficacy. In this study, we prepared a recombinant SDF-1 alpha containing a collagen binding domain (CBD-SDF-1 alpha) and developed a functional collagen scaffold by tethering CBD-SDF-1 alpha on the collagen scaffold for in situ tendon regeneration. CBD-SDF-1 alpha 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-1 alpha, enhancing the recruitment of fibroblast-like cells and providing instructive microenvironment and mechanical support for tendon regeneration. Therefore, CBD-SDF-1 alpha-modified. collagen scaffold could serve as a practical application for tendon regeneration. (C) 2018 Elsevier Ltd. All rights reserved.