Enhanced wound healing in diabetic rats by nanofibrous scaffolds mimicking the basketweave pattern of collagen fibrils in native skin

Nanofibrous scaffolds that offer proper microenvironmental cues to promote the healing process are highly desirable for patients with chronic wounds. Although studies have shown that fiber organization regulates cell behaviors in vitro, little is known about its effects on the wound healing process in vivo. Most of the nanofibrous scaffolds currently used in skin repair are randomly oriented. Herein, inspired by the basketweave-like pattern of collagen fibrils in native skin, we fabricated biomimetic nanofibrous scaffolds with crossed fiber organization via electrospinning. The regulation of crossed nanofibrous scaffolds on fibroblasts was compared with that of aligned and random nanofibrous scaffolds. Unexpectedly, crossed nanofibrous scaffolds induced different cellular responses in fibroblasts, including differences in cellular morphology, migration and wound healing related gene expression, in comparison to either aligned or random nanofibrous scaffolds. More importantly, the regulation of nanofibrous scaffolds with different fiber organizations on wound repair was systematically investigated in diabetic rats. While the healing processes were enhanced by all nanofibrous scaffolds, wounds treated with crossed nanofibrous scaffolds achieved the best healing outcome, which was evidenced by the resolution of inflammation, the accelerated migration of fibroblasts and keratinocytes, and the promotion of angiogenesis. These findings helped reveal the role of fiber organization in regulating the wound healing process in vivo and suggest the potential utility of biomimetic crossed nanofibrous scaffolds for the repair of chronic wounds.