Extracellular RNA Biomarkers for Chronic Non-Healing Wounds

Chronic non-healing wounds represent a major clinical challenge, often associated with diabetes, vascular insufficiencies and aging. Despite the substantial burden that such wounds place on patients and healthcare systems, few biomarkers have been approved for prediction of wound healing trajectories and outcomes, limiting opportunities to inform clinical management decisions or quantify patient responses to interventions. Recent advances have identified cell-free nucleic acids as powerful tools for gaining molecular insights because they offer a non-invasive, dynamic snapshot of physiological and pathological processes occurring throughout the body. In particular, cell-free RNAs from non-coding RNA families including microRNA, long non-coding RNA, circular RNA and transfer RNA fragments can be profiled on a large scale to reveal novel disease signatures to support biomarker development. The presence of such non-coding RNAs in serum, plasma or other biofluids provides a rich resource for uncovering new parameters that can support biomarker development for wound repair. In this review article, we highlight some of the current challenges associated with biomarkers for wound healing in clinical practice. We then survey the microRNAs, long non-coding RNA and circular RNAs landscape in relation to their utility as biomarkers in diabetic foot ulcers and other chronic wounds. Collectively, these extracellular RNAs offer a multifaceted view of wound biology and may serve as non-invasive biomarkers for stratifying wound severity, predicting healing outcomes and guiding personalised interventions.