Microenvironment-responsive collagen hydrogel with Houttuynia Cordata Thunb vesicles for diabetic wound repair.

Wound healing in diabetic patients is often impaired due to a combination of tissue inflammation, excessive reactive oxygen species (ROS), insufficient neovascularization, and pH imbalances. To overcome these challenges, we designed a multifunctional hydrogel system capable of responding to the wound microenvironment and enabling the controlled release of plant-derived extracellular vesicles (PDEVs) to accelerate diabetic wound healing. The hydrogel was constructed using recombinant human Type III collagen (rhCOL3) grafted with 3-aminophenylboronic acid (APBA) to gain the microenvironment response ability. Additionally, PDEVs derived from Houttuynia cordata thunb (HC-EVs) were embedded within the hydrogel to improve the biological ability. This HC-EVs-loaded BA-rhCOL3 hydrogel (HC-EVs@B-CH) demonstrates excellent tissue adhesion, self-healing properties, and notable antioxidant and anti-inflammatory effects. By regulating the wound microenvironment, it significantly enhances diabetic wound healing through improved angiogenesis, increased collagen deposition, and reduced inflammation. Mechanism studies have shown that HC-EVs@B-CH can regulating both NF-κB and YAP pathways, which may be the underlying biological mechanism for its role in promoting the healing of diabetic wounds. In summary, this HC-EVs@B-CH offers a multifunctional, innovative solution for diabetic wound care. Its ability to address key barriers in wound healing highlights its potential as a next-generation wound dressing for effective diabetic wound management.