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

Fractional carbon dioxide (AFCO 2 ) laser therapy is used for treating pathological scarring, but the clinical outcomes are variable and the mechanisms of scar reduction poorly understood. We investigated the mechanisms underpinning efficacy of AFCO 2 laser therapy, performing single-cell RNA sequencing in skin biopsies from patients with hypertrophic scars after AFCO 2 laser therapy. Patients with younger scars (Good Responder, GR, <6 years from healing) had better scar reduction than patients with older scars (Poor Responder, PR, >6 years from healing) by various measures of scarring. scRNAseq 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 responses ( IL-12 , MSTN, HLA-DQA ). The groups had distinct intercellular communication networks and differentiation trajectories after AFCO 2 , with regenerative Mesenchymal fibroblasts associated with a good response and inflammatory Secretory Papillary and Inflammatory Fibroblasts with a poor response.