Mild Heat Stimulating and Microenvironment Reprogramming Hydrogel for Accelerating Diabetic Wound Healing

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Wound Healing

Background:

• Diabetic wounds present complex challenges including hyperglycemia, oxidative stress, inflammation, and poor angiogenesis.
• Current treatments for diabetic wounds are often suboptimal, necessitating innovative therapeutic strategies.

Purpose of the Study:

• To develop a green synthesized, mild heat-stimulating hydrogel (C-4-N) for reprogramming the diabetic wound microenvironment.
• To evaluate the efficacy of the C-4-N hydrogel in promoting diabetic wound healing in a preclinical model.

Main Methods:

• Fabrication of C-4-N hydrogel using L-arginine, protocatechuic aldehyde, Compound K, α-lipoic acid-modified chitosan, and 4-arm-PEG-SH.
• Investigated synergistic mechanisms including ROS scavenging, glucose regulation, and macrophage polarization modulation.
• Assessed wound healing in a diabetic rat model with mild photothermal stimulation.

Main Results:

• The C-4-N hydrogel demonstrated synergistic reprogramming of the wound microenvironment.
• Achieved near-complete wound closure (99.49%) in diabetic rats by day 13 with mild photothermal stimulation.
• Showcased enhanced re-epithelialization, collagen deposition, vascular maturation, and improved systemic glucose control.

Conclusions:

• The green synthesized C-4-N hydrogel offers a promising therapeutic strategy for chronic diabetic wound management.
• Mild photothermal stimulation synergistically enhances the hydrogel's efficacy in promoting wound healing.
• This study establishes a novel paradigm for microenvironment reprogramming in diabetic wound care.