Oleoyl-Chitosan-Based Nanofiber Mats Impregnated with Amniotic Membrane Derived Stem Cells for Accelerated Full -Thickness Excisional Wound Healing

Wound healing management is a major challenge for critical full thickness skin wounds. Development of nanofibrous scaffolds with tunable wettability, degradation, and biocompatibility are highly desirable. Herein, we demonstrated synthesis of oleoyl chitosan (OC) by grafting monounsaturated fatty acid residue, C-18 oleoyl chain, to the backbone of chitosan molecule and blending with gelatin to form the nanofiber mats. The physicochemical properties of the nanofiber mats revealed mechanical strength, moderate surface wettability, and suitable degradation rate. The nanofibrous mats showed excellent in vitro cytocompatibility with human amniotic membrane-derived stem cells (HAMSCs) in terms of enhanced adhesion and proliferation owing to biomimetic nanoarchitecture and chemical cues. Furthermore, the fabricated nanofiber was implanted with and without preseeded HAMSCs in the full thickness wound to evaluate the skin wound healing efficacy in a rat model. Histological and immunohistochemical studies were conducted to evaluate the plausible changes of tissue architecture and expression of molecular markers involved in wound healing process. Both acellular and HAMSCs incorporated cellular nanofibers promoted wound contraction remarkably with superior skin tissue regeneration in terms of enhanced collagen synthesis, re-epithelialization and initiation of epithelial cells stratification compared to control group.