Continuous Self-Oxygenated Double-Layered Hydrogel under Natural Light for Real-Time Infection Monitoring, Enhanced Photodynamic Therapy, and Hypoxia Relief in Refractory Diabetic Wounds Healing

The human health is still threatened by refractory keratitis and diabetic foot ulcers caused by bacterial infections, hypoxia, and chronic inflammation, so that patients are exposed to the risk of amputation, vision loss, and even death. Herein, an oxygen-producing double-layered hydrogel is developed that can visualize bacterial infections and supply oxygen to enhance antimicrobial photodynamic therapy (PDT) and inflammation alleviation for diabetic wounds healing. The inner layer hydrogel (containing oxidized sodium alginate/carboxymethyl chitosan [CMCS] via Schiff-base) is incorporated with a photodynamic metal–organic framework (PCN-224) and a pH indicator (bromothymol blue). The outer layer hydrogel (containing agarose and CMCS) loads photosynthetic cyanobacteria that continuously generate oxygen to relieve hypoxia of tissue and enhance antimicrobial PDT efficiency. Meanwhile, some unique advantages are reflected by continuous oxygen supply under natural light, such as cell migration acceleration, inflammation relief, promotion of skin capillary formation, and wound tissue recovery. Therefore, the self-oxygenated double-layered hydrogel offers tremendous benefits in the synergistic treatment of refractory anaerobe wounds from timely infection monitoring to tissue repair.