Optimal tension facilitates wound healing in a full-thickness ex vivo human skin model

The use of human skin models is a widely accepted approach for studying skin biology. These models include organotypic systems reconstructed from human cells as well as models based on discarded surgical tissue. Cell-based systems are time-consuming to set up and maintain, are unable to fully recapitulate the differentiated architecture of the skin, and typically lack minor skin cell populations. Traditional full-thickness skin models prepared from excised skin tissue collected during surgery quickly lose viability and the ability to respond to stimuli once off the body. Traction-force balance is essential for maintaining skin homeostasis and is, therefore, an important factor in regulating both tissue structure and physiological function. Here we describe a tension-based skin explant model to address the unmet need for a human skin model that reliably mimics in vivo skin even in complex biological processes such as wound response and healing. This tension-based model mimics an in vivo-like response to laser ablative wounding, with keratin 17 observed throughout the wounded skin sample, whereas only minimal expression is observed in skin cultured without tension. Additionally, observation of the wound sites for up to 3 weeks shows that reformation of the basement membrane is highly dependent on the presence of tension. qPCR analysis of a variety of wound healing markers also showed a delayed and diminished response to wounding in non-tensioned skin compared to skin cultured at optimal tension. Application of optimized tension can therefore restore skin’s inherent mechanobiology, enabling a more in vivo-like behavior, greatly increasing the utility of full-thickness ex vivo skin models. Conflict of interest: MJC and RPH are founders and directors of Ten Bio Ltd, a company focused on development of ex vivo skin models.