Logic-Based Diagnostic and Therapeutic Nanoplatform with Infection and Inflammation Monitoring and Microenvironmental Regulation Accelerating Wound Repair

Infectious cutaneous wounds are a thorny clinical problem. The microenvironment of the infectious wound is complicated and changes at different healing stages. Traditional treatments either have a single effect such as anti-inflammation, antibacteria, or angiogenesis or a simple mixture of several functions. They fail to deal with the change of the physiological healing process, leading to unsatisfactory outcomes. Herein, we have designed a logic-based smart nanoplatform (named as ZEM), aiming to self-monitor the wound microenvironment and accordingly react to the changes of the healing process, fitting multiple needs of physiological repair at different stages. ZEM was synthesized using zeolitic imidazolate framework-8 (ZIF-8) coated with an epigallocatechin gallate (EGCG)/Mg2+ complex. We characterized ZEM in the aspects of morphology, physical and chemical properties, and ion release pattern. At the initial stage, ZEM sensed the weakly acidic environment and responsively released a large number of zinc ions to eliminate bacterial infection. Then came the second inflammation stage, where ZEM responded to the oxidative stress of the local wound area with EGCG absorbing excessive reactive oxygen species (ROS), contributing to the downregulation of intracellular ROS. Meanwhile, local inflammation was alleviated by reducing the expression of proinflammatory M1 phenotype factors (IL-6, TNF-α, and IL-1β). Since the balance of local ROS had been achieved, the resulting disintegration of the EGCG/Mg2+ complex gave rise to the sustainable release of Mg2+ at the proliferation stage, promoting vascularized healing. In vivo animal experiments further proved the diagnostic and therapeutic functions of ZEM. All these results demonstrated that ZEM was a promising treatment strategy in soft tissue engineering.