A multifunctional hydrogel co-encapsulating ROS-responsive quercetin nanoparticles and ADSCs to accelerate infected wound healing

Qu@NPs/ADSCs@CS-gel integrates anti-inflammatory, antibacterial, immunomodulatory properties for infected wound healing. • Hydrogel with genipin-crosslinked chitosan/silk sericin, encapsulated ADSCs, and surface-attached ROS-responsive Qu@NPs. • Qu@NPs release quercetin in response to ROS, effectively scavenging ROS and reducing inflammation while preserving SOD activity. • Hydrogel inhibits M1 polarization & inflammatory cytokines, promotes M2 transition & creates regenerative microenvironment. • Enhances antibacterial, proliferation, re-epithelialization, angiogenesis, collagen deposition, accelerates wound repair. Chronic infected wounds face healing challenges due to the interplay of persistent infection, excessive inflammation, and impaired angiogenesis. Conventional dressings often address only one pathological aspect, resulting in limited therapeutic effects. To overcome these barriers, we developed a multifunctional hydrogel Qu@NPs/ADSCs@CS-gel that integrates anti-inflammatory, antibacterial, and immunomodulatory activities. The system was fabricated from genipin-crosslinked chitosan and silk sericin into a biocompatible hydrogel (CS-gel) that exhibits antibacterial activity and permits cellular matrix permeability. Adipose-derived stem cells (ADSCs) were encapsulated within this hydrogel, while reactive oxygen species (ROS)-responsive quercetin-loaded nanoparticles (Qu@NPs), based on poly(propylene sulfide)-poly(ethylene glycol) (PPS-PEG), were attached to its surface. Upon wound contact, Qu@NPs are released from Qu@NPs/ADSCs@CS-gel, and PPS-PEG breaks down in response to ROS to release quercetin, effectively eliminating ROS and alleviating the inflammatory response, thereby establishing a regenerative microenvironment for ADSC-mediated repair. Qu@NPs/ADSCs@CS-gel exhibited potent antibacterial activity, reduced ROS accumulation in macrophages while preserving superoxide dismutase (SOD) activity. Furthermore, it inhibited M1 macrophage polarization and pro-inflammatory cytokine secretion, while promoting transition to the M2 phenotype. These effects collectively improved cell proliferation, re-epithelialization, angiogenesis, and collagen deposition, accelerating the three phases of wound repair. Our findings support Qu@NPs/ADSCs@CS-gel as an advanced dressing for infected wounds.