Bioinspired Multifunctional Hydrogel Loaded with Netrin-1 for Diabetic Wound Healing

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Wound Healing Research

Background:

• Diabetic wound healing is impaired by fibroblast dysfunction.
• Netrin-1 shows potential in reversing high-glucose-induced fibroblast dysfunction.
• Developing effective treatments for chronic diabetic wounds remains a significant challenge.

Purpose of the Study:

• To develop a biomimetic dual-network hydrogel loaded with Netrin-1 (SA/GA@Netrin-1) for promoting diabetic wound healing.
• To investigate the hydrogel's mechanism of action, including its effects on fibroblast autophagy and function.
• To evaluate the therapeutic efficacy of the SA/GA@Netrin-1 hydrogel in a diabetic rat wound model.

Main Methods:

• Fabrication of a dual-network hydrogel using sodium alginate (SA) and glycyrrhizic acid (GA) with octopus-inspired adhesive structures.
• Loading Netrin-1 into the hydrogel for sustained release and protection.
• Assessment of hydrogel properties, including adhesion, biocompatibility, antioxidant, and antimicrobial effects.
• In vitro studies on fibroblast behavior (migration, collagen synthesis) under hyperglycemic conditions.
• In vivo evaluation of wound healing in diabetic rats, including histological analysis and assessment of inflammation and autophagy.

Main Results:

• The SA/GA@Netrin-1 hydrogel demonstrated strong adhesion and sustained release of Netrin-1.
• Netrin-1 promoted autophagy by activating the AMPK-mTOR pathway, reversing high-glucose-induced fibroblast dysfunction.
• The hydrogel exhibited antioxidant and antimicrobial properties.
• In vivo studies showed enhanced collagen deposition, reduced inflammation, and accelerated wound closure in diabetic rat models.
• The hydrogel significantly improved diabetic wound healing compared to controls.

Conclusions:

• The SA/GA@Netrin-1 hydrogel is an effective therapeutic agent for promoting diabetic wound healing.
• The hydrogel's mechanism involves restoring fibroblast function through autophagy modulation.
• This biomimetic hydrogel represents an innovative strategy for managing chronic diabetic wounds and potentially other refractory wound types.