Antibacterial Vitamin K3 Carnosine Peptide-Laden Silk Fibroin Electrospun Fibers for Improvement of Skin Wound Healing in Diabetic Rats

Abstract

The utilization of a multifunctional bioactive molecule functionalized electrospun dressing in tissue repair and regenerative function is a prominent therapeutic strategy for preparing efficient biomaterials to promote chronic wound healing. Designing robust and highly efficient antibacterial agents in resistance against microbes and bacterial infections is a key challenge for accelerating diabetic wound healing until today. In this study, we developed a vitamin K3 carnosine peptide (VKC)-laden silk fibroin electrospun scaffold (SF-VKC) for diabetic wound healing. The structural confirmation of synthesized VKC was characterized by ¹H NMR, ¹³C NMR, electrospray ionization mass spectrometry (ESI-MS), and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy analysis, and the cell viability of VKC was evaluated by the CCK-8 assay in HFF1 and NIH 3T3 cells. VKC shows excellent cell viability on both cell lines, and the VKC and SF-VKC electrospun mats exhibited excellent antibacterial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. Prepared SF and SF-VKC fibrous mats were well characterized, and the SF-VKC nanofiber mat presented good biodegradability, adhesiveness, unique mechanical property, expedient water uptake property, sustained drug release, and excellent biocompatibility for chronic wound healing. The in vitro tissue engineering study depicted excellent cell migration and cell-cell interaction in the NIH 3T3 cells over the VKC-impregnated silk fibroin (SF-VKC) mat. A higher population of cell migration was observed in cells' denuded area (scratched region) compared to the native SF fibrous mat. Interestingly, our results demonstrated that the prepared VKC-impregnated SF mat had potentially promoted the STZ-induced diabetic wound healing in a shorter period than the pure SF mat. Thus, obtained in vitro and in vivo outcomes suggest that the VKC-laden SF electrospun fibrous mat could be a better and inexpensive fibrous antibacterial biomaterial to elicit earlier re-epithelialization and efficient matrix remodeling for accelerating chronic infected wound reconstruction in skin diabetic wound healing applications.

Keywords: antibacterial; diabetic wound healing; electrospun; silk fibroin; vitamin K3-carnosine peptide.