Mechanoregulative hydrogel enables scar-reduced and functional healing of infected diabetic mobile wounds

Diabetic infected wounds at mobile sites are characterized by persistent hyperglycemia, oxidative stress, and drug-resistant bacterial colonization, which collectively establish a self-amplifying infection-inflammation cycle. Meanwhile, wounds located at mechanically active regions, such as the nape and joints, are continuously exposed to stretching and repetitive deformation, leading to heterogeneous stress distribution at the wound edge, fibrotic remodeling, and hypertrophic scar formation. Therefore, simultaneous regulation of biochemical pathology and mechanical imbalance is essential for high-quality healing of diabetic mobile wounds. Here, we develop a multilevel mechanoregulative hydrogel to coordinately regulate the bio-mechanical microenvironment of diabetic infected wounds at mobile sites. The inner dynamic boronate ester network functions as a glucose-responsive delivery platform for on-demand release of polyhexamethylene biguanide (PHMB) and oxidative stress-balancing OPC-Ce nanoparticles (OPC-Ce NPs), enabling efficient eradication of drug-resistant bacteria, ROS scavenging, and inflammatory microenvironment remodeling. The outer elastic network absorbs, disperses, and homogenizes wound-edge forces to reconfigure local stress distribution, thereby suppressing fibrosis activation in high-stress regions while improving impaired cellular activity in low-stress regions. In addition, the outer layer recaptures excess PHMB, reducing cytotoxicity associated with prolonged antibacterial exposure. In vivo, this hydrogel markedly promotes ordered regeneration of diabetic mobile wounds, as evidenced by normalized epidermal differentiation, enhanced hair follicle neogenesis, restrained dermal fibroblast overactivation, and functional remodeling of neovasculature and extracellular matrix. This study establishes a therapeutic strategy that integrates anti-infective/anti-inflammatory regulation, dynamic antibacterial agent management, and mechanical stress regulation, offering a new materials paradigm for scar-reduced repair of infected diabetic wounds on mobile joints.