Single-cell and spatial multi-omics of keloids and hypertrophic scars: shared repair programmes and candidate multicellular niches

Keloids and hypertrophic scars (HS) share fibrotic repair programmes but differ in growth beyond wound boundaries and their tendency to regress. Single-cell and spatial studies can help explain how similar cellular programmes produce different tissue outcomes. This narrative review compares human scar studies with mechanistic experiments. POSTN-richfibroblast states recur in keloids and HS, but their spatial distributions differ between studies: dispersedmesenchymal fibroblasts in one keloid study contrast with deep, vessel-associated signals in another. Thesefindings support a shared matrix-producing programme more strongly than a uniform anatomical compartment.We define multicellular niches as local tissue microenvironments and distinguish their observed organisationfrom hypotheses about their function. A candidate fibrovascular niche comprises activated fibroblasts andnearby endothelial cells in deep keloid dermis; the hypothesis is that local signalling sustains matrixproduction and vascular activation. Neural–stromal studies instead link fibroblast–Schwann-cellcommunication to itch and pain. Experiments connect PIEZO1-dependent calcium entry to YAP activity inkeloid fibroblasts, epidermal FOSL1–MED1 regulation to MMP3-dependent fibroblast activation, andmacrophage-derived lactate to MCT1-dependent fibroblast responses in HS. Shared matrix-producing fibroblast programmes occur in both scar types, while spatial studies report different tissue arrangements. Functional experiments identify mechanical, epidermal and metabolic inputs to profibrotic activity. How these inputs are organised locally and contribute to persistent growth or symptoms remains to be established.