Abstract
Recruiting endogenous stem cells to deliver signaling molecules is an attractive therapeutic strategy for the treatment of skin injuries. Although various signaling molecule delivery techniques have been developed, they are limited in their ability to accurately mimic the natural physiological process in which stem cells are recruited via signaling molecule concentration gradients. Hence, herein, we developed an approach to generate persistent signaling molecule concentration gradients in microscale gel arrays. Signaling molecule concentration gradients were established in each microscale gel via chemical conjugation and were maintained for >12 days. Moreover, the microscale gel provided a suitable environment for bone mesenchymal stem cells (BMSCs) growth, with many BMSCs migrating toward the stromal cell-derived factor-1 alpha (SDF-1α) gradient in vitro. Subsequently, a patch was formulated by mounting a microscale gel array on an adhesive layer and designated as the SDF-1α gradient microscale gel array patch. In a murine full-thickness skin defect model, this patch effectively increased the recruitment of endogenous BMSCs, accelerated wound healing, and enhanced neovascularization. Moreover, the regenerated tissue was more similar to normal skin tissue, as evidenced by histological analysis. The SDF-1α gradient microscale gel array patch also proved its efficacy in a diabetic animal model. Taken together, our findings indicate that the microscale gel array system developed in this study provides an innovative strategy for accelerating wound healing by creating well-defined and localized SDF-1α gradients in vivo. Furthermore, the patch-like design will facilitate on-demand use, thereby further aiding with wound healing.