Spatial exploration of immune cell heterogeneity in skin functional scar-less wound regeneration model at single-cell resolution

Abstract

Inevitable skin scarring devoid of dermal appendages bring about unfavorable effects on both aesthetic and physiological functions. Here we offered an available method for large-area wound regeneration using biodegradable Aligned extracellular matrix (ECM) scaffold. Accelerating wound coverage and enhanced hair follicle (HF) neogenesis were observed with the implantation of biomaterials. Multimodal analysis during wound regeneration provides a unique lens through which we can explore the foreign body responses (FBR) around biomaterials. First, we identified cell heterogeneity in responses to ECM scaffolds using single-cell RNA sequencing. Next the spatial anchor highlighted preferential recruitment of T cells around biomaterials colocalized with hair follicle precursor cells. Reconstruction of signaling pathways suggested the pro-regenerative effect of the adaptive immune systems on HF neogenesis. Immunodeficient mice lacking mature T lymphocytes lost the ability to activate papillary fibroblast as well as stimulate HF regeneration, validating the potential therapeutic effect of the adaptive immune system activated by biomaterials. In conclusion, this study provided the further understanding of the FBR and facilitate the design of immunoregulatory biomaterials for biomedical application in the future.