Cellular heterogeneity in hypertrophic burn scars in response to carbon dioxide laser therapy

Ablative fractional carbon dioxide (AFCO2) laser therapy is widely used for treating pathological scarring, with promising clinical results. However, mechanisms underlying reduction hypertrophic scarring are poorly understood. We investigated the cellular mechanisms of AFCO2 laser therapy by performing single-cell RNA sequencing (scRNA-seq) on skin biopsies from burn survivors with hypertrophic scars before and after AFCO2 therapy. Those with a good response (GR) to laser therapy, assessed objectively and subjectively, generally had scars less than 6 years from injury, whereas poor responders (PR) had more mature scars over 6 years since injury. Additionally, scRNA-seq analysis revealed that genes enriched in GR were associated with extracellular matrix and structure organisation (COL14A1, POSTN, SPARC); whereas genes enriched in PR were related to enhanced immune inflammatory responses (CXCL14, JUN, TNC). Distinct intercellular communication networks and differentiation trajectories were observed after AFCO2, with regenerative mesenchymal fibroblasts predominating in GR but inflammatory fibroblasts associated with PR.