m6A RNA tags may shape chronic wound healing phase by phase, review finds

A review published in Molecular Biology Reports argues that N6-methyladenosine (m6A) RNA methylation, a chemical modification of RNA that acts as a layer of post-transcriptional regulation, may be a key player in the biology of chronic wounds. The authors, led by Xingkai Yin and Shudong Sun, propose that durable healing depends on coordinated control of inflammation, vascular repair, and matrix remodeling, and that m6A modification influences all three processes.

Crucially, the review stresses that m6A effects are not uniform. They 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. Because each cell type responds differently, the authors conclude that these findings do not support a uniform systemic intervention.

Instead of endorsing a single therapy, the review frames a testable question: whether local, time-limited delivery of m6A-targeting agents can achieve target engagement without disrupting repair in other cell compartments. This phase-matched concept motivates the engineering of biomaterials designed to release their payload at the right stage of wound healing.

The review synthesizes the evidence by wound phase and etiology, and distinguishes direct wound studies from biological analogies drawn from other tissues. It also evaluates the biomaterial functions required for local exposure, controlled release, and durable-repair assessment, providing a framework for designing stage-matched delivery systems.

The authors emphasize substantial remaining gaps. Human-relevant validation, pharmacokinetics, manufacturing, and long-term safety are all unresolved, meaning that m6A-based wound therapies remain far from clinical application. As a review, the article does not present new experimental data but organizes existing findings and outlines the research needed before biomaterial-based m6A interventions could be tested in patients.

Subject of Research: The role of m6A RNA methylation in chronic wound healing and biomaterial-based interventions.

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

Article References: Yin, X., Liu, J., Li, H., Zhang, C., Fan, L., Wang, K., & Sun, S. (2026). Navigating the phase-dependent m⁶A landscape in chronic wounds: engineering biomaterials for stage-matched intervention and durable repair. Molecular Biology Reports, 53(1), Article 1851. https://doi.org/10.1007/s11033-026-13048-3

Image Credits: AI Generated

DOI: 10.1007/s11033-026-13048-3

Keywords: m6A, RNA methylation, chronic wounds, diabetic wounds, biomaterials, drug delivery, wound healing, keratinocytes, macrophages, fibroblasts, endothelial cells, post-transcriptional regulation