Tetrazine-Enhanced Donor-Acceptor-Donor Photosensitive Metal-Organic Frameworks for Combating Drug-Resistant Bacteria and Accelerating Diabetic Wound Healing

Multidrug-resistant (MDR) bacterial infections and chronic wounds pose significant challenges in modern healthcare, de-manding innovative treatment approaches. In this study, we introduce two new donor-acceptor-donor (D-A-D) photosensi-tive metal-organic frameworks (MOFs) featuring tetrazine as a potent electron acceptor. By incorporating tetrazine, we en-hance reactive oxygen species (ROS) generation while simplifying synthesis, resulting in efficient charge separation and boosted ROS production. Functionalized with L-arginine, the resulting composites, A@Zn-TDP and A@Ni-TDP, release both ROS and nitric oxide (NO) upon visible light activation, creating a dual-action mechanism that efficiently combats bacteria and accelerates wound healing. In vitro tests against MRSA, E. coli, and S. aureus demonstrate robust antibacterial activity, while in vivo studies reveal significantly accelerated wound closure, reduced bacterial load, and enhanced collagen deposi-tion and vascularization. This dual-action platform offers a powerful tool for tackling drug-resistant infections and promot-ing tissue regeneration in complex wounds, opening new avenues for advanced therapeutic solutions in challenging clinical settings.