Development of carboxymethyl chitosan gelatin scaffold embedded with Vitamin E for Wound healing applications

Abstract

Traditionally, antimicrobials (such as antibiotics, antiseptics, etc.) are typically used to treat open wounds, but antimicrobial resistance (AMRs) has emerged as one of the severe health dangers of the 21st century. Further, with the evolution of resistant microbes outpacing the discovery of new antimicrobials, especially antibiotics, alternates are urgently required both to reduce the emergence of AMR and find effective solutions for treating wounds devoid of antimicrobials. The present research deals with the development of carboxymethyl chitosan (CMCh)-gelatin (Gel) crosslinked bioscaffolds embedded with dl-and#945; tocopherol acetate for wound healing.Initially, twenty-four scaffolds were developed using two crosslinkers glutaraldehyde (GA) and copper oxide nanoparticles (CuO), and were characterized to select two lead scaffold combinations. Further chemicals binding interaction of CMCh, Gel, and GA crosslinked scaffold with receptors participating in wound healing Viz. GSK-3, COX-2, TNF- and#945;, VEGFR-2, and TGF-and#946;1 were predicted using molecular docking studies. Using two lead scaffolds combinations from the initial study, six more scaffolds (SV1-SV6) were developed and embedded with dl-and#945; tocopherol acetate and these scaffolds were further evaluated. On the basis of evaluation studies, further three lead scaffolds were subjected to antioxidant, cytocompatibility, sterility, and antimicrobial studies. In comparison, finally, two scaffolds were subjected to dermal toxicity and in-vivo wound healing studies. At last long-term stability studies of these scaffolds were carried out according to ICH guidelines.