Infection-driven proliferative phase impairment in chronic wounds: a mechanistic framework for precision regenerative therapy

Chronic wounds represent a major clinical challenge characterized by persistent failure of tissue repair, a phenomenon that cannot be fully explained by infection and inflammation alone. Emerging evidence indicates that wound-associated microbial communities establish stable pathogenic ecosystems that specifically disrupt the proliferative phase of healing, the critical stage responsible for cellular expansion, angiogenesis, and extracellular matrix reconstruction.

Here, we propose the conceptual framework of infection-driven proliferative phase impairment (IDPPI), which describes a pathological state in chronic wounds wherein sustained microbial pathogenic activities continuously compromise host regenerative programs. We synthesize current evidence showing that coordinated virulence factor deployment, biofilm persistence, and host immune–metabolic dysregulation converge to induce proliferative arrest.

They do so through direct cellular injury, suppression of repair-related signaling pathways, and disruption of cell-cycle control. This integrated pathogenic cascade ultimately locks wounds into a state of low-efficiency or arrested regeneration.