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

Abstract

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.

Self-Adaptive Antibiofilm Effect and Immune Regulation by Hollow Cu2MoS4 Nanospheres for Treatment of Implant Infections

“…Therefore, ideal therapeutic agents should be able to adaptively modulate the proinflammatory response in macrophages according to the conditions of implant infections. As reported, the pH microenvironment changes from acidic to neutral before and after biofilm elimination. − To confirm this microenvironment change in the implant infection mouse model, the pH of the infected tissues around implants was tested on the 2nd and 4th days after treatment. As shown in Figure S19, the infected tissues were acidic on the 2nd day in all groups.…”

“…Although this sequential regulation strategy is promising, it cannot adaptively regulate the immune response to different infection treatment stages, which may influence the therapeutic efficacy due to the unsuitable action onset of antimicrobials or immunomodulators. At the infection stage, bacteria and immune cells often cause an acidic microenvironment through anaerobic fermentation and respiration. , When the infection is controlled, the lesion site returns to a neutral microenvironment. , Given this, the development of microenvironment-responsive therapeutic agents with self-adaptive antibiofilm activity and inflammatory modulation properties is promising for the treatment of implant infections.…”

Advances in metal–organic framework-based hydrogel materials: preparation, properties and applications

“…8, Wang et al presented a self-oxygenated hydrogel, which is very helpful for enhanced photodynamic therapy (PDT) against bacterial infection and rapid detection as well as continuous oxygen generation to promote wound healing. 248 Notably, the inner layer hydrogel consisted of carboxymethyl chitosan (CMCS) and oxidized sodium alginate (OSA) via a Schiff-base reaction. Then, it was utilized to combine bromothymol blue (BTB) and MOFs (PCN-224).…”

A dual-modal ROS generator based on multifunctional PDA–MnO2@Ce6 nanozymes for synergistic chemo-photodynamic antibacterial therapy

“…12,13 However, PDTmediated continuous O 2 depletion hinders the production of singlet oxygen ( 1 O 2 ) in the hypoxic environment. 14,15 CDT is limited by low catalytic efficiency. 16,17 Therefore, it is difficult to effectively eliminate bacteria by a single modal therapeutic strategy.…”