Adhesive, injectable, and ROS-responsive hybrid polyvinyl alcohol (PVA) hydrogel co-delivers metformin and fibroblast growth factor 21 (FGF21) for enhanced diabetic wound repair

Abstract

As conventional treatments for diabetic wounds often fail to achieve rapid satisfactory healing, the development of effective strategies to accelerate diabetic wound repair is highly demanded. Herein, fibroblast growth factor 21 (FGF21) and metformin co-loaded multifunctional polyvinyl alcohol (PVA) hydrogel were fabricated for improved diabetic wound healing. The in vitro results proved that the hydrogel was adhesive and injectable, and that it could particularly scavenge reactive oxygen species (ROSs), while the in vivo data demonstrated that the hydrogel could promote angiogenesis by recruiting endothelial progenitor cells (EPCs) through upregulation of Ang-1. Both ROSs’ removal and EPCs’ recruitment finally resulted in enhanced diabetic wound healing. This work opens a strategy approach to diabetic wound management by combining biological macromolecules and small chemical molecules together using one promising environmental modulating drug delivery system.

The role of FGF-21 in promoting diabetic wound healing by modulating high glucose-induced inflammation

“…In this study, our results indicate that FGF-21 treatment restored hyperglycemic damage on endothelial cell proliferation, migration, and tube-forming ability while reducing cell death rates, reflecting its protective effect on endothelial function in diabetic wounds. Encapsulating FGF-21 and dimethyldigua in ROS hydrogel has also been proposed as a potential new drug delivery system for diabetic wounds, with significant therapeutic effects observed in animal experiments [ 29 ]. These findings highlight the potential of innovative drug delivery systems for FGF-21 to enhance its therapeutic efficacy in treating diabetic wounds.…”

A Glucose-Responsive Hydrogel Platform Based on Poly(vinyl alcohol) for Enhanced Diabetic Wound Healing

“…Therefore, it is urgent to design a new program to promote the healing of diabetic wound. Many studies have applied PVA hydrogels to the treatment of diabetic foot, and some success has been achieved, mainly reflected in the antibacterial and antioxidant effects on wound surface and the provision of pro-repair growth factors. − However, these hydrogels also have some shortcomings to a certain extent. There is still room for improvement in bonding strength; it is difficult to provide adequate and effective protection for the wound, and the mechanical strength needs to be further strengthened.…”

Hydrogel-based dressings designed to facilitate wound healing

“…The hydrogel system offers a means to maintain the bioactivity of growth factors, facilitating their delivery to diabetic wounds and promoting angiogenesis at the wound site. 290 Hao et al proposed a CMCS hydrogel that incorporated fibroblast growth factor. Experimental findings revealed that the hydrogel promoted neovascularization in diabetic wounds by upregulating the expression of CD31 and CD34, thereby enhancing the wound healing process.…”