Tissue expansion procedures (TE) utilize mechanical forces to induce skin growth and regeneration. While the impact of quick mechanical stimulation on molecular changes in cells has been studied extensively, there is a clear gap in knowledge about sequential biological processes activated during long-term stimulation of skin in vivo. Here, we present the first genome-wide study of transcriptional changes in skin during TE, starting from 1 h to 7 days of expansion. Our results indicate that mechanical forces from a tissue expander induce broad molecular changes in gene expression, and that these changes are time-dependent. We revealed hierarchical changes in skin cell biology, including activation of an immune response, a switch in cell metabolism and processes related to muscle contraction and cytoskeleton organization. In addition to known mechanoresponsive genes (TNC, MMPs), we have identified novel candidate genes (SFRP2, SPP1, CCR1, C2, MSR1, C4A, PLA2G2F, HBB), which might play crucial roles in stretched-induced skin growth. Understanding which biological processes are affected by mechanical forces in TE is important for the development of skin treatments to maximize the efficacy and minimize the risk of complications during expansion procedures.

Tissue expansion (TE) is a clinical procedure that stimulates skin growth through repetitive mechanical stretching. 1,2 Despite a long history of clinical application, the molecular mechanisms involved in skin response to TE are still largely unknown. Porcine skin is used extensively in biomedical research to study wound healing, infectious disease and radiation, because it closely resembles the human homologue. 3 Given this, porcine became an excellent animal model to study the mechanical properties and molecular mechanisms of TE. [4][5][6][7][8] Our previous study on genome-wide transcriptional changes in TE revealed that mechanical forces from the expander activate pathways related to immune response, metabolism, muscle contraction and cytoskeleton organization in a time-dependent manner. 4 We

No abstract