Injectable PVP / CMC Hydrogels With Tissue Adhesion, Hemostatic Function and Sustained Drug Release

ABSTRACT Injectable hydrogels that can be delivered through minimally invasive procedures and conform to irregular wound geometries are attractive for treating highly exudative wounds. However, achieving durable adhesion on tissue‐mimetic substrates, together with controlled local therapy and early‐stage protection against bleeding and oxidative stress, remains challenging. Here, a calcium‐crosslinked semi‐interpenetrating poly( N ‐vinylpyrrolidone) (PVP)/Carboxymethyl cellulose (CMC) hydrogel incorporating procaine (PC) is reported, with the PVP‐CMC‐P2 formulation selected as a representative multifunctional dressing that integrates adhesion, sustained local analgesia, antioxidant protection, and hemostatic performance. Beyond its pharmacological role, PC functions as a design‐integrated supramolecular modulator, promoting ion‐pairing and hydrogen‐bonding interactions that reinforce the network, regulate swelling, degradation, and release profiles. The PVP‐CMC‐P2 hydrogel exhibits shear‐thinning injectability and significant self‐healing behavior, recovering approximately 82% of its storage modulus after 1000% strain. Adhesion testing demonstrated strong interfacial performance, achieving lap shear strengths of up to 1091 kPa on dry metal substrates and approximately 200 kPa on gelatin‐coated tissue‐mimetic surfaces. In vitro evaluation confirmed favorable blood compatibility, with low hemolysis (2.1% ± 0.4%) and accelerated clot formation. Overall, this study identifies a drug‐modulated semi‐IPN design that couples injectability, self‐healing, and adhesive hemostatic function for managing highly exudative wounds.