Adipose-Derived Stromal Cell-Sheets Sandwiched, Book-Shaped Acellular Dermal Matrix Capable of Sustained Release of Basic Fibroblast Growth Factor Promote Diabetic Wound Healing
Xin Shi, Liyuan Jiang, Xin Zhao, Bei Chen, Wei Shi, Yanpeng Cao, Yaowu Chen, Xiying Li, Yusheng He, Chengjie Li, Xiaoren Liu, Xing Li, Hongbin Lü, Can Chen, Jun Liu
Abstract
The management of diabetic wounds is a therapeutic challenge in clinical settings. Current tissue engineering strategies for diabetic wound healing are insufficient, owing to the lack of an appropriate scaffold that can load a large number of stem cells and induce the interaction of stem cells to form granulation tissue. Herein we fabricated a book-shaped decellularized dermal matrix (BDDM), which shows a high resemblance to native dermal tissue in terms of its histology, microstructure, and ingredients, is non-cytotoxic and low-immunogenic, and allows adipose-derived stromal cell (ASC) attachment and proliferation. Then, a collagen-binding domain (CBD) capable of binding collagen was fused into basic fibroblast growth factor (bFGF) to synthetize a recombinant growth factor (termed as CBD–bFGF). After that, CBD–bFGF was tethered onto the collagen fibers of BDDM to improve its endothelial inducibility. Finally, a functional scaffold (CBD–bFGF/BDDM) was fabricated. In vitro and in vivo experiments demonstrated that CBD–bFGF/BDDM can release tethered bFGF with a sustained release profile, steadily inducing the interaction of stem cells down to endothelial differentiation. ASCs were cultured to form a cell sheet and then sandwiched by CBD–bFGF/BDDM, thus enlarging the number of stem cells loaded into the scaffold. Using a rat model, the ASC sheets sandwiched with CBD–bFGF/BDDM (ASCs/CBD–bFGF/BDDM) were 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 be applicable for diabetic wound healing.