The structural properties of biomaterials play crucial roles in guiding cell behavior and influencing immune responses against the material. We fabricated electrospun membranes with three types of surface topography (random, aligned, and latticed), introduced them to dorsal skin excisional wounds in mice and rats, and evaluated their effects on wound healing and immunomodulatory properties. An overview of different immune cells in the microenvironment with the help of single-cell RNA sequencing revealed diverse cellular heterogeneity in vivo. The time course of immune response was advanced toward an adaptive immunity-dominant stage by the aligned scaffold. In mice without mature T lymphocytes, lack of wound-induced hair neogenesis indicated a regulatory role of T cells on hair follicle regeneration. The microenvironment around scaffolds involved an intricate interplay of immune and cutaneous cells.
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