Stimuli-responsive nanovesicles for spatiotemporal control of drug delivery in chronic cutaneous wounds: Bridging molecular pathobiology to translational nanomedicine

Abstract

Chronic skin wounds remain a challenging clinical problem due to persistent inflammation, poor blood vessel growth, and biofilm infections that impede healing. Traditional therapies often lack the precision for targeted drug delivery, limiting their effectiveness. In response, stimuli-responsive nanovesicles have emerged as a promising alternative. These carriers are engineered to release drugs in response to unique biochemical and biophysical signals in the wound environment. They react to internal cues such as acidic pH, oxidative stress, and elevated protease activity, as well as external triggers like near-infrared light or ultrasound. For example, pH-sensitive polymer matrices and oxidation-labile linkers have been developed to protect drugs and ensure precise release at the target site. Surface modifications with integrin-binding peptides and zwitterionic coatings improve cellular uptake and reduce immune detection, extending therapeutic action. Advances in preclinical evaluation now include 3D-bioprinted skin models and microfluidic organ chips that simulate real wound conditions, allowing detailed study of nanoparticle penetration and biological activity. Murine studies have further supported these findings by demonstrating reduced bacterial colonization and improved tissue regeneration via tracking the immune responses. However, challenges such as scaling up production and meeting stringent regulatory standards remain. Future integration with smart bandages and machine learning may further optimize drug release and dosing, paving the way for more effective chronic wound care.