A Triple-Functional Nanoplatform for Oxidative Stress-Driven Pressure Ulcer Therapy

Pressure ulcers (PUs) are chronic wounds driven by persistent inflammation, oxidative stress, impaired angiogenesis, and delayed remodeling, yet current treatments remain suboptimal. Here, we developed a novel nanocomposite (CCH) by loading cerium oxide (CeO₂) and curcumin into hollow mesoporous silica nanoparticles (HMSN). CCH exhibited well-defined spherical morphology, favorable particle size, and pH-dependent drug release. Mechanistically, CCH possessed potent superoxide dismutase (SOD)- and catalase (CAT)-mimetic activities, effectively scavenging reactive oxygen species. In vitro, CCH was efficiently internalized by HUVECs, showed excellent biocompatibility up to 100 μg/mL, protected HUVECs from oxidative damage by reducing intracellular ROS and restoring VEGF secretion, and induced anti-inflammatory M2 macrophage polarization. In a mouse model of pressure ulcer, topical CCH application significantly accelerated wound closure, enhanced re-epithelialization and granulation tissue formation, reduced systemic CRP and PCT levels, and improved scar prognosis, associated with increased VEGF expression and CD31-positive vascularization, along with organized collagen deposition. Collectively, CCH integrates antioxidant, anti-inflammatory, pro-angiogenic, and tissue-remodeling functions into a single nanoplatform, effectively addressing key pathological features of PUs. Thus, CCH represents a promising and safe candidate for chronic wound management.