Abstract In pathological microenvironments of diabetes, neuroinflammation, arthritis and other chronic diseases marked by oxidative stress, chronic inflammation, and bacterial infection, severely disrupt cellular physiological functions leading to failure of tissue regeneration. Existing therapeutic strategies are difficult to achieve simultaneous pathological causative factor removal and tissue regeneration due to the cascading pathological reactions triggered by endogenous enzyme insufficiency. Biomimetic artificial enzymes have been used to remodel pathological microenvironments, but the lack of precise structural design and unclear structure‐performance relationships limit their catalytic activities. As a new generation of enzyme‐like materials, atomically precise metal cluster enzymes (MCEs) can mimic the spatial hierarchical structure of natural enzymes and significantly enhance the enzyme‐like activity by regulating the configuration of the metal core and ligand, which is expected to enable pathological microenvironment repair. This review summarizes the design and controllable synthesis of atomically precise MCEs. The precise regulatory mechanisms of cluster enzymes are systematically analyzed for their mechanism of action in tissue repair microenvironments. In addition, the application of atomically precise MCEs for tissue regeneration in pathological microenvironments is discussed in detail. Finally, the future potential of atomically precise MCEs in pathological tissue regeneration is envisioned as perspectives.
Xiong et al. (2026) studied this question.