Carboxymethyl chitosan hydrogel reinforced by endothelial cell derivatives for angiogenesis and full-thickness wound healing

Abstract

Schematic illustration depicting the preparation of methacrylate-modified carboxymethyl chitosan hydrogel enriched with endothelial cell derivatives (ECd@M−CMCS) and its application in promoting angiogenesis and facilitating full-thickness wound healing. • The hydrogel scaffold containing specific ECM within M−CMCS was successfully prepared. • It features a loose porous 3D structure, excellent hydrophilicity, and water absorption. • It enables adaptability to wound shapes and a moist healing microenvironment. • It demonstrates strong antimicrobial activity and has multiple biological functions. • It enhances wound healing and improves both healing speed and quality. Wound self-repair is prone to forming hard-to-heal chronic wounds due to infections, vascular damage, diabetes and other factors. Selecting the appropriate treatment and dressing can help prevent the deterioration of chronic wounds and facilitate the restoration of normal structure and function. Carboxymethyl chitosan (CMCS)-modified hydrogels can promote tissue repair, while human umbilical vein endothelial cell derivatives (ECd) enhance self-repair. In this study, ECd was prepared into lyophilized powder using vacuum freeze-drying to preserve its original active ingredients. In vitro experimental results revealed that a specific concentration of ECd effectively supported cell proliferation, migration and angiogenesis. ECd was further encapsulated in the designed glycidyl methacrylate-modified carboxymethyl chitosan (M−CMCS) hydrogel. The optimal combination of ECd and M−CMCS hydrogel (ECd@M−CMCS) was evaluated by testing the material properties, analyzing cellular behaviors and assessing antimicrobial effects. Sprague Dawley rat models (tail-breaking, liver incision, skin whole-layer defect) demonstrated ECd@M−CMCS exhibited good biocompatibility and enhanced wound healing and hemostasis in vivo .