Next-generation smart polymeric hydrogels for chronic wound management: integrating antimicrobial, immunomodulatory and regenerative strategies

Abstract

Wound healing is a tightly orchestrated sequence of hemostatic, inflammatory, proliferative, and remodeling events, yet chronic wounds arise when this cascade is dysregulated by persistent infection, excessive oxidative stress, and biofilm formation. Such pathological conditions particularly in diabetic and vascular-compromised patients sustain inflammatory signaling, impair angiogenesis, and disrupt extracellular matrix (ECM) turnover. In this study, we comprehensively evaluated these pathological barriers while presenting an integrated overview of recent advances in multifunctional smart hydrogels engineered to overcome them. Rather than treating antimicrobial, immunomodulatory and regenerative functions as independent therapeutic categories, this review established a microenvironment material function translation framework emphasizing their temporal and spatial coordination. We further critically examined dynamic network chemistries, nanocomposite and multicomponent architectures, advanced 3D/4D fabrication, AI-assisted formulation and wound monitoring, preclinical model limitations, manufacturing scalability and regulatory barriers. By distinguishing promising proof-of-concept strategies from technologies approaching clinical translation, this review identifies design principles for safer, more reproducible and clinically relevant smart hydrogel systems. Finally, we addressed translational barriers including scalability, regulatory classification, and long-term biocompatibility and outline future directions for AI-integrated, patient-specific hydrogel systems. Collectively, this study provides a comprehensive technical assessment of next-generation polymeric hydrogels as precision platforms for advanced wound management.