<p>The traditional skin graft wound repair strategy for burns is unable to reconstruct the normal anatomy of the skin, resulting in quality problems such as scarring, which have always been the bottleneck of burn medicine. The skin rete ridge (RRs) is an important basis for maintaining skin homeostasis, but the complete reconstruction of the RRs in wound repair is still difficult with traditional split-thickness skin grafting and wound cell therapy. In this study, based on our previous experience of wound epidermal stem cell (EpiSCs) therapy, we further designed and optimized the bionic RRs microneedles loaded with human EpiSCs (C-Ms). Transplanting C-Ms into full-thickness wounds in nude mice promotes the formation of RRs similar to natural human epidermis and provides stem cell niches. Pathway enrichment analysis showed that C-Ms transplantation into wounds reshapes the extracellular matrix (ECM) and reduces wound healing fibrosis through FAK, ECM receptor interaction signaling pathways. Moreover, C-Ms improve wound healing by accelerating early vascularization, and they also regulate the proliferation of EpiSCs to further promote the formation of RRs structure. These results suggest that C-Ms can compensate for the lack of skin anatomical structure, which may be suitable for use in clinical patients with large-scale burns.</p> Graphical abstract <p></p>