Stimuli-Responsive Polymeric Nanoparticles for Controlled Release in Chronic Wound Care

Abstract

Chronic wounds -- diabetic foot ulcers, venous leg ulcers, and pressure injuries -- affect an estimated 6.5 million patients in the United States alone, at an annual treatment cost exceeding US$25 billion, yet the conventional dressings used to manage them remain largely passive barriers that cannot sense or respond to the wound's own biochemistry. This article synthesizes the literature on stimuli-responsive polymeric nanoparticles engineered specifically to close that gap in chronic wound care. We trace the pathophysiological basis for triggered release -- the elevated and variable pH, sustained protease activity, oxidative burden, and infection-associated heating that distinguish a non-healing wound bed from intact skin -- and review how pH-, enzyme-, redox-, thermal-, and light-responsive polymer chemistries, developed largely in oncology, have been adapted into nanoparticle, nanocomposite-hydrogel, and nanofiber architectures for topical antimicrobial and growth-factor delivery. Particular attention is given to protease-gated release systems that exploit the same matrix metalloproteinase dysregulation responsible for degrading therapeutic payloads in chronic wounds. Read together, the evidence supports stimuli-responsive nanoparticle-based dressings as a coherent and increasingly well-evidenced engineering pattern for active wound care, while leaving biofilm penetration, rodent-to-human translational validity, manufacturing reproducibility, and multi-trigger system design as an open research agenda.