Dual-function thermoresponsive antibiotic-loaded hydrogel with antimicrobial and osteogenic properties for implant-related infection control

Implant-related infections demand advanced biomaterials capable of delivering localized, sustained antimicrobial activity while supporting tissue repair. Here, we present an engineered thermoresponsive hydrogel based on poly(N-vinylcaprolactam) (PNVCL), designed as a dual-function platform that enables temperature-triggered gelation, controlled tetracycline release, and osteogenic support. The PNVCL network was tailored to provide rapid sol-gel transition at physiological temperature, strong adhesion to moist surfaces, injectability into narrow implant geometries, high swelling capacity, slow degradation, and a stable drug-release profile-properties rarely combined within a single hydrogel system. To evaluate material performance, we employed a tiered biological framework comprising cytocompatibility assays, controlled physicochemical analyses, and antimicrobial testing against complex, polymicrobial biofilms, complemented by human <i>in situ</i> and <i>in vivo</i> multispecies infection models. The PNVCL-tetracycline hydrogel demonstrated potent antibacterial activity, preserved human gingival fibroblast viability, and sustained its structural integrity and release characteristics even under infection-associated inflammatory conditions. <i>In vivo</i>, the material simultaneously reduced bacterial burden, modulated pathogenic community structure, and promoted new bone formation with a higher degree of maturation, confirming its dual antimicrobial and osteogenic behavior. By integrating precisely engineered thermoresponsive behavior, controlled drug delivery, robust mechanical and interfacial properties, and validated biological functionality, this PNVCL-tetracycline hydrogel represents a material-driven, clinically relevant solution for treating implant-related infections.