Enzymatically functionalized RGD-gelatin scaffolds that recruit host mesenchymal stem cells in vivo and promote bone regeneration

Critical-size bone defects are imposing a substantial biomedical burden. Despite being long regarded as a potential approach to mitigate this burden or an alternative to bone grafts, bone tissue engineering (BTE) has virtually not proceeded to widespread clinical practices. In the BTE field, it is highly required to find a facile method to prepare active scaffolds with tailored biological functions. Here, we immobilized cell adhesive RGD motifs onto gelatin sponge (GS) scaffolds through enzymatic linking. On the basis of the resulting RGD-functionalized GS (RGD/GS) scaffolds, we developed a new and convenient strategy for bone defect repair, in which the scaffolds were first used to recruit mesenchymal stem cells (MSCs) from skeletal muscle, immediately followed by their engraftment into bone defect. We demonstrated significantly enhanced host cells homing into RGD/GS scaffolds as a result of specific RGD-integrin interactions, and the recruited host cells showed a strong osteogenic differentiation potential. After ectopic implantation of cell-laden RGD/GS scaffolds into critical-size mouse bone defects, marked bone tissue regeneration occurred. The presented strategy not only provides an agile route for the preparation of bioactive scaffolds and the construction of osteoinductive bone-graft substitutes, but also avoids or minimizes the complicated and laborious cell isolation, in vitro expansion and cell seeding procedures used in the conventional BTE.