Neuroimmunomodulation in chronic wounds: an opinion

The skin’s integrity and functionality are repaired through a series of processes that are conducted in a systematic and timely manner during wound healing (WH). The process of wound regeneration following an injury is significantly influenced by neurogenic stimuli; this is illustrated by the discovery that delayed wound repair occurs in animal models after the surgical removal of cutaneous nerves. In addition, recent studies suggest that glial support cells may be key players in wound repair, and skin wounding triggers glial dedifferentiation and proliferation. In confirmation of this hypothesis, ablation of injury-activated glia leads to reduced tumor growth factor (TGF) β signaling and impaired wound repair. Skin wounding may damage the cutaneous vasculature and innervation, with axotomy studies in zebrafish enabling live imaging of the clearance of axon debris by macrophages and epidermal cells. The relationship between innervation and repair is reciprocal, with wounding triggering increased cutaneous nerve sprouting in some contexts