Single-cell–guided repositioning of Sorafenib enables nano-immunotherapy for scarless burn healing

Burn-induced hypertrophic scarring is driven by persistent inflammation and fibroblast activation, yet current biomaterial strategies rarely address both components with mechanistic precision. Here, we report a microneedle-integrated coordination nanoplatform (GA-Sorafenib@MN) that simultaneously disrupts immune-mediated chemotaxis and fibrotic signaling to promote scarless regeneration of burn wounds. The design was guided by single-cell transcriptomic analysis of keloid tissue, which identified TGF-b1 as a fibroblast-specific fibrotic driver, and Sorafenib as the top therapeutic candidate via high-throughput virtual screening. To enhance solubility and anti-inflammatory performance, Sorafenib was coordinated with gallium (III), forming GA–Sorafenib nanoparticles subsequently embedded into photo-crosslinked HAMA microneedles. Mechanistically, GA-Sorafenib@MN suppresses CXCL2/CXCR2-driven macrophage chemotaxis and TGF-b/Smad3-mediated fibroblast activation, while inhibiting NLRP3 inflammasome and TLR4/NF-kB signaling. This reprograms the immune–fibrotic axis at the wound site, mitigates collagen I/III deposition, and restores ECM integrity. Our strategy establishes a transcriptomics-guided material design paradigm, enabling spatiotemporal modulation of structural immunity and offering a highly translatable solution for scarless healing of non-infectious burn wounds.