A Multifunctional ε-Polylysine/Hyaluronic Acid Hydrogel Promotes Diabetic Wound Healing by Orchestrating...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Wound Healing

Background:

• Diabetic wound healing is impaired by a harsh microenvironment including high glucose, inflammation, infection, oxidative stress, and poor vascularization.
• Hydrogel dressings with microenvironmental regulation capabilities are crucial for treating diabetic wounds.

Purpose of the Study:

• To develop an ultraviolet in situ crosslinked hydrogel (D@H/E) loaded with desferrioxamine (DFO) for diabetic wound management.
• To evaluate the hydrogel's physicochemical properties and its efficacy in a mouse model of diabetic wounds.

Main Methods:

• Fabrication of a hydrogel using methacrylic anhydride modified hyaluronic acid (HA-MA) and glycidyl methacrylate modified ε-polylysine (EPL-GMA), loaded with DFO.
• Characterization of hydrogel properties and evaluation of its efficacy in streptozotocin (STZ)-induced hyperglycemic mice.

Main Results:

• The DFO-loaded hydrogel exhibited significant ROS scavenging (80.8% DPPH radical scavenging) and antibacterial activity (>99.8% inhibition against S. aureus and E. coli).
• The hydrogel accelerated wound closure in diabetic mice by day 14, promoting M2 macrophage polarization, angiogenesis, and alleviating ferroptosis.
• Mechanistic studies showed upregulated CD206, angiogenesis factors, and GPX4 expression.

Conclusions:

• The D@H/E hydrogel system synergistically addresses ROS, infection, inflammation, and ferroptosis, effectively remodeling the diabetic wound microenvironment.
• This DFO-loaded hydrogel presents a promising therapeutic platform for managing chronic diabetic wounds.