Fibroblast State Switching Orchestrates Dermal Maturation And Wound Healing

The study proposed a model where a negative feedback loop between extracellular matrix (ECM) deposition and fibroblast proliferation determined dermal architecture in murine dermis. It was found that fibroblast behavior switched between proliferating and depositing ECM, which was necessary to define dermal architecture. Virtual-tissue simulations predicted that fibroblast migration was only required for wound healing, not for maintaining homeostatic tissue architecture. In vivo live imaging confirmed that tissue architecture was achieved without active cell migration, while both proliferation and migration were crucial for tissue repair after wounding. This interdependence of cell proliferation and ECM deposition was identified as a key factor in tissue-scale coordination, suggesting potential therapeutic strategies for enhancing skin regeneration.