Adipose-Derived Stromal Cell-Sheets Sandwiched, Book-Shaped Acellular Dermal Matrix Capable of Sustained Release of Basic Fibroblast Growth Factor Promote Diabetic Wound Healing

The management of diabetic wounds is still a therapeutic challenge in clinics. Current tissue-engineering strategies for diabetic wound healing are insufficient owing to lacking an appropriate scaffold that can largely load stem cells and induce the interacted stem cells forming granulation tissue. Herein, we fabricated a book-shaped decellularized dermal matrix (BDDM). This BDDM shows a high resemblance to native dermal tissue in histology, microstructure and ingredients, is noncytotoxicity and low-immunogenicity, as well as allows adipose-derived stromal cells (ASCs) attachment and proliferation. And then, we prepared a recombinant basic fibroblast growth factor (termed as CBD-bFGF) capable of binding collagen, and then tethered on the collagen fibers of BDDM to improve the endothelial inducibility of BDDM. Finally, a functional scaffold (CBD-bFGF/BDDM) was fabricated. In-vitro and in-vivo experiments showed that the CBD-bFGF/BDDM can release the tethered bFGF with a sustained release profile, steadily inducing the interacted stem cells down endothelial differentiation. After that, ASCs were cultured to form a cells-sheet, and then sandwiched by the CBD-bFGF/BDDM, thus enlarging the number of stem cells loading in the scaffold. Using a rat model, the ASC-sheets sandwiched CBD-bFGF/BDDM (ASCs/CBD-bFGF/BDDM) are capable of enhancing the formation of granulation tissue, promoting angiogenesis, and facilitating collagen deposition and remodeling. Therefore, the findings of this study demonstrate that ASCs/CBD-bFGF/BDDM could serve as a potential application for diabetic wound healing.