Not all approaches to changing the behavior of cells so as to spur greater regeneration must necessarily involve drugs. Here researchers demonstrate that ultrasound can partially compensate for age-related deficiency in skin healing, and catalog some of the cellular biochemistry involved. This isn't a case of fixing the proximate cause of faltering wound healing, a decline in one specific type of cell signaling, but rather activating another mechanism that can act as a substitute to some degree. As the publicity materials note, deploying this treatment to the clinic should not be too much of a challenge given the present widespread use of ultrasound for other purposes:
Chronic skin healing defects are one of the leading challenges to lifelong wellbeing, affecting 2-5% of populations. Chronic wound formation is linked to age and diabetes and frequently leads to major limb amputation. Here we identify a strategy to reverse fibroblast senescence and improve healing rates.
In healthy skin, fibronectin activates Rac1 in fibroblasts, causing migration into the wound bed and driving wound contraction. We discover that mechanical stimulation of skin with ultrasound can overturn healing defects by activating a calcium/CamKinaseII/Tiam1/Rac1 pathway that substitutes for fibronectin-dependent signaling and promotes fibroblast migration. Treatment of diabetic and aged mice recruits fibroblasts to the wound bed and reduces healing times by 30%, restoring healing rates to those observed in young, healthy animals. Ultrasound treatment is equally effective in rescuing the healing defects of animals lacking fibronectin receptors, and can be blocked by pharmacological inhibition of the CamKinaseII pathway. Finally, we discover that the migration defects of fibroblasts from human venous leg ulcer patients can be reversed by ultrasound, demonstrating that the approach is applicable to human chronic samples.
By demonstrating that this alternative Rac1 pathway can substitute for that normally operating in skin, we identify future opportunities for management of chronic wounds.