Mechanically Robust PVA/SA Semi-IPN Hydrogel for Higheffective Temperature-Triggered Linagliptin Delivery

Hydrogels with excellent mechanical properties and high drug-delivery capacity are highly advantageous for wound healing applications. However, reconciling mechani-cal properties with drug-delivery performance remains challenging. Herein, a semi-interpenetrating polymer network (semi-IPN) hydrogel composed of poly(vinyl alcohol) (PVA) and sodium alginate (SA) was fabricated via freeze-thaw cycling. Through component optimization, this hydrogel achieved a unique combination of de-sirable properties, including softness (Young’s modulus of 32.5 kPa), high stretchability (fracture strain of 283.9%), and high water-content (96.46%). Linagliptin (LIN), a DPP-4 inhibitor crucial for diabetic wound repair, was loaded into the system with an effective loading efficiency of 89.25%. The hydrogel system demonstrated tempera-ture-responsive release kinetics: minimal release occurred at low temperatures, while rapid, sustained release at physiological temperature was achieved, reaching a cumu-lative release efficiency of up to 85.17%, which was highly beneficial for the storage and application of drug-loaded hydrogels. This study presents a hydrogel platform with effectively integrates material robustness, temperature-triggered drug delivery and high-efficiency loading and releasing LIN, which showcases significant potential as a novel therapeutic material for diabetic wound healing.