Precision strategies for enhanced chronic skin wound healing using multifunctional hydrogels

Chronic skin wounds persist because conventional dressings and systemic therapies often fail to simultaneously control infection, resolve dysregulated inflammation, and promote tissue regeneration. Multifunctional hydrogels provide a conformable, programmable platform to localise therapy and coordinate these processes. This review synthesizes design principles across natural, synthetic matrices and addresses micro/nanostructural tuning to balance biocompatibility, degradability and mechanical adaptation to heterogeneous wound beds. We classify integrated nanofillers by function, antimicrobial (e.g., Ag, Cu, ZnO), redox-active and antioxidant (e.g., CeO 2 , Se), pro-regenerative and conductive carbon-based fillers, and stimulus-responsive modules (light/PTT-PDT, pH/redox, enzyme, ultrasound, and electrical). We map their mechanisms to infection control, immune rebalancing, angiogenesis and re-epithelialization. Additionally, we summarize bioactive functional fillers (such as antimicrobial peptides; EGF, VEGF, TGF-β, PDGF, and SDF-1) and strategies for spatiotemporally controlled release. An evaluation pipeline links in vitro assessments of cytocompatibility, antimicrobial and anti-inflammatory activities to in vivo efficacy in infected and diabetic wound models, alongside practical assays of adhesion, mechanics properties, and degradation. Translational considerations include the safety of nano-enabled systems, sterilization compatibility, cost-efficient scale-up and harmonized quality control. Finally, we identify priorities for precision wound care and highlight opportunities for machine learning to accelerate matrix, enabling sensor-guided, closed-loop therapy for chronic skin wounds. • Overview of the application of multifunctional hydrogels for enhanced chronic skin wound healing. • The design strategies and response models of multifunctional hydrogels for wound healing and precision strategies are summarized. • The prospects and challenges for the clinical translation and development of multifunctional hydrogels for chronic skin wound healing are outlined.