Encapsulation of Equisetum hyemale Extract in Immunomodulatory Collagen–Polyurethane–Dextran Semi-Interpenetrating Network Hydrogels Attenuates Cytotoxicity and Accelerates Diabetic Wound Healing

Equisetum hyemale extract promotes wound healing in diabetic rats, but its cytotoxicity limits its use. This study aimed to encapsulate the extract in collagen–polyurethane–dextran semi-interpenetrating network hydrogels containing 20–30 wt% dextran and 20–40 wt% extract. The physicochemical properties, in vitro biological responses, and wound-healing performance of the hydrogels were subsequently evaluated. The hydrogels exhibited crosslinking degrees of 65–80%, swelling capacities of 2800–3100%, predominantly elastic behavior, and structural integrity for up to 30 days under hydrolytic and proteolytic conditions. The D20C20 formulation (20% dextran and 20% extract) showed the greatest polyphenol permeation (940 µg/mL after 120 h) and permeability coefficient (Kp = 9.9 × 10−3 cm/h). Cell viability varied depending on the formulation, cell type, and exposure time. Macrophages and mononuclear cells exhibited transient increases in the MTT-derived viability signal after 24 h, followed by decreases after 72 h. However, fibroblast viability remained consistent across formulations. Most formulations increased IL-10 and reduced MCP-1 in lipopolysaccharide-stimulated macrophages after 72 h. No hemolysis or dermal irritation occurred under the tested conditions. In diabetic rats, D20C20 achieved complete wound closure by day 17. The regenerated tissue exhibited a more organized collagen arrangement. These findings support further investigation of D20C20 as a potential wound-healing material.