Biofilm-Responsive Nanoplatforms for Infected Wound Reconstruction

Abstract

Abstract Antibiotic-resistant, biofilm-infected wounds are a major clinical challenge because bacterial persistence is embedded within a broader pathological wound ecosystem characterized by chronic inflammation, oxidative stress, hypoxia, vascular dysfunction, impaired extracellular matrix remodeling, and defective tissue regeneration. Conventional antimicrobial strategies may reduce planktonic bacteria but often fail to eradicate mature biofilms or restore the biological conditions required for durable healing. This review critically examines biofilm-responsive nanoplatforms as stage-adaptive, interface-aware, and translationally disciplined therapeutic systems for reprogramming chronic infected wounds toward regenerative repair. Rather than treating these platforms as nanoscale antibiotic carriers, we emphasize their potential to coordinate sequential wound needs: early extracellular polymeric substance disruption, pathogen suppression, and local niche penetration, followed by immune recalibration, redox balance restoration, angiogenic support, and matrix reconstruction. Across metallic, oxide, polymeric, lipid, silica, metal–organic framework, and two-dimensional nanomaterial systems, therapeutic performance is governed by both material composition and integration into wound-facing interfaces such as hydrogels, electrospun dressings, multilayer patches, microneedles, injectable depots, and biofabricated scaffolds. These interfaces determine retention, activation, penetration depth, and biological timing. We further highlight that multifunctionality must be balanced against a “complexity tax”: additional responsive elements are clinically justified only when they address defined biological barriers that simpler systems cannot overcome. We conclude that biofilm-responsive wound nanomedicine must move beyond bacterial killing alone toward validated wound-ecosystem regulation, with stronger emphasis on mature biofilm models, polymicrobial infection, human-relevant tissue testing, long-term scar quality, and reproducible manufacturing. This disciplined design approach is essential for translating biofilm-responsive nanoplatforms from laboratory constructs into clinically credible tools for tissue reconstruction.