Scar formation is the primary outcome of tissue injury repair in mammals, affecting patients' appearance and function. How fascia-derived fibroblasts coordinate tissue repair during deep wound healing, and how they distinguish between pathological scarring and regenerative healing, has long been an important scientific question in this field.

On December 25, 2025, Professor YE Haifeng from our Institute / School of Basic Medical Sciences / Burn, Plastic Surgery and Wound Repair Medical Center of the First Affiliated Hospital of Nanchang University published a research paper titled "Distinct fibroblast assemblies establish scarless regeneration" in Cell Reports, revealing the mechanism by which fascial fibroblast supracellular assembly patterns regulate tissue repair and scarless regeneration.

The fascia is a connective tissue layer located beneath the skin and serves as an important source of fibroblast progenitor cells in the injury response. However, the mechanisms by which deep tissue fibroblasts coordinate optimal wound repair at the tissue level remain unclear.

The researchers established a multimodal fascia explant culture system. Combined with lineage-specific reporter mice and live imaging technology, they tracked wound fibroblasts for up to 5 days and discovered that fascial fibroblasts form three spatiotemporally ordered supracellular assembly patterns during healing: sprouting → reticulating → clustering. Using the Prestwick compound library for high-throughput drug screening, the research team found:

• The organizational patterns of fibroblasts are more predictive of wound healing outcomes than traditional extracellular matrix deposition markers;

• Two classes of therapeutic compounds were identified: compounds that block reticulation/clustering can inhibit scar formation; compounds that block early sprouting (fluvastatin, thiostrepton, and fenbendazole) can prevent pro-inflammatory fibroblast/myofibroblast differentiation, promote angiogenesis, and reduce inflammatory infiltration;

• Treatment with these three drugs can achieve scarless regenerative healing, accompanied by hair follicle regeneration.

This study reveals that fibroblast supracellular assembly is a fundamental feature of tissue repair, providing new therapeutic targets and drug repurposing strategies for wound healing and fibrotic diseases.

Professor YE Haifeng is the first author of the paper, and Professor Yuval Rinkevich from the Chinese Academy of Medical Sciences is the corresponding author. This project was supported by the National Natural Science Foundation of China (82572888, 82402919) and the Jiangxi Provincial Natural Science Foundation (20252BAC200109).