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

Abstract

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.

Migration and Phenotype Control of Human Dermal Fibroblasts by Electrospun Fibrous Substrates

“…The quantitative migrated cell number was performed by nucleus immunostaining (Figure b) and plotted in Figure c. The number of migrated HDFs on AF was significantly higher than that on RF, indicating AF advanced HDFs migration when compared with RF, which was consistent with published reports 11a,24. However, these cell migration investigations were performed in endpoint assays, which may be exposed to interference that arises from cell growth.…”

Electrospinning and emerging healthcare and medicine possibilities

“…Therefore, scaffolds with crossed nanofibers showed higher keratinocytes and fibroblasts migration rate, thus better wound healing performance than either random or unidirectionally aligned nanofibers. 56 A highly porous cotton-wool-like PCL/chitosan scaffold was developed using emulsion electrospinning and achieved accelerated full-thickness wound healing in 3 weeks in vivo. 57 One major concern for wound healing is scar inhibition, which is a long-lasting obstacle in clinical studies.…”

Skin wound healing assisted by angiogenic targeted tissue engineering: A comprehensive review of bioengineered approaches

“…For example, Sun et al mimicked the basketweave‐like pattern of collagen fibrils in native skin and investigated its effect on chronic wound healing in diabetic rats. Despite most nanofibrous scaffolds, which are randomly oriented, crossed fiber organization caused the best healing outcome with an increase in migration of fibroblasts and keratinocytes as well as induction of angiogenic response 127 …”