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.

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Implanted biomaterials such as medical catheters are prone to be adhered by proteins, platelets and bacteria due to their surface hydrophobicity characteristics, and then induce related infections and thrombosis. Hence, the development of a versatile strategy to endow surfaces with antibacterial and antifouling functions is particularly significant for blood-contacting materials. In this work, CuSO 4 /H 2 O 2 was used to trigger polydopamine (PDA) and poly-(sulfobetaine methacrylate) (PSBMA) co-deposition process to endow polyurethane (PU) antibacterial and antifouling surface (PU/PDA(Cu)/PSBMA). The zwitterions contained in the PU/PDA(Cu)/PSBMA coating can significantly improve surface wettability to reduce protein adsorption, thereby improving its blood compatibility. In addition, the copper ions released from the metal-phenolic networks (MPNs) imparted them more than 90% antibacterial activity against E. coli and S. aureus . Notably, PU/PDA(Cu)/PSBMA also exhibits excellent performance in vivo mouse catheter-related infections models. Thus, the PU/PDA(Cu)/PSBMA has great application potential for developing multifunctional surface coatings for blood-contacting materials so as to improve antibacterial and anticoagulant properties.

Low-temperature photothermal therapy (PTT) systems constructed by integrating organic photothermal agents with other bactericidal components that initiate bacterial apoptosis at low hyperthermia possess a promising prospect. However, these multicomponent low-temperature PTT nanoplatforms have drawbacks in terms of the tedious construction process, suboptimal synergy effect of diverse antibacterial therapies, and high laser dose needed, compromising their biosafety in ocular bacterial infection treatment. Herein, a mild PTT nanotherapeutic platform is formulated via the self-assembly of a pH-responsive phenothiazinium dye. These organic nanoparticles with photothermal conversion efficiency up to 84.5% necessitate only an ultralow light dose of 36 J/cm2 to achieve efficient low-temperature photothermal bacterial inhibition at pH 5.5 under 650 nm laser irradiation. In addition, this intelligent mild photothermal nanoplatform undergoes negative to positive charge reversion in acid biofilms, exhibiting good penetration and highly efficient elimination of drug-resistant E. coli biofilms under photoirradiation. Further in vivo animal tests demonstrated efficient bacterial elimination and inflammatory mitigation as well as superior biocompatibility and biosafety of the photothermal nanoparticles in ocular bacterial infection treatment. Overall, this efficient single-component mild PTT system featuring simple construction processes holds great potential for wide application and clinical transformation.

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