Innervated\nCoculture Device to Model Peripheral Nerve-Mediated\nFibroblast Activation

Cutaneous wound healing is a complex process involving\nvarious\ncellular and molecular interactions, resulting in the formation of\na collagen-rich scar with imperfect function and morphology. Dermal\nfibroblasts are crucial to successful wound healing, migrating to\nthe wound site where they are activated to provide extracellular matrix\nremodeling and wound closure. Peripheral nerves have been shown to\nplay an important role in wound healing, with loss or damage to these\nnerves often leading to impaired healing and the formation of chronic\nnonhealing wounds. Previous research has suggested that sensory nerves\nsecrete trophic factors that can regulate wound healing, including\nfibroblast activation; however, the direct cell–cell interaction\nbetween nerves and fibroblasts has not been extensively studied. To\naddress this knowledge gap, we developed an <i>in vitro</i> co-culture model using a device called the IFlowPlate. This model\nsupports the long-term viability of multiple cell types while allowing\nfor direct contact between sensory nerve cells and dermal fibroblasts.\nUsing the IFlowPlate, we demonstrate that co-culture of dorsal root\nganglia with dermal fibroblasts increases fibroblast proliferation,\ncollagen and α-smooth muscle actin expression, and secretion\nof pro-wound healing factors, suggesting that nerves can promote wound\nhealing by modulating fibroblast activation. The IFlowPlate offers\na user-friendly and high-throughput platform to study the in vitro\ninteractions between nerves and a variety of cell types that can be\napplied to wound healing and other important biological processes.