Navigating the phase-dependent m⁶A landscape in chronic wounds: engineering biomaterials for stage-matched intervention and durable repair

Durable healing of chronic wounds requires coordinated control of inflammation, vascular repair, and matrix remodeling. N⁶-methyladenosine (m⁶A) RNA methylation is a candidate layer of post-transcriptional regulation in these processes, but its effects are cell-, target-, phase-, and disease-context dependent. The current direct evidence is concentrated in diabetic wound models, where distinct m⁶A-associated mechanisms have been reported in keratinocytes, endothelial cells, macrophages, and fibroblasts. These findings do not support a uniform systemic intervention. Instead, they motivate the testable question of whether local, time-limited delivery can achieve target engagement without disrupting repair in other cell compartments. This review synthesizes the evidence by wound phase and etiology, distinguishes direct wound studies from biological analogies, and evaluates biomaterial functions required for local exposure, controlled release, and durable-repair assessment. We emphasize the remaining gaps in human-relevant validation, pharmacokinetics, manufacturing, and long-term safety.