An Autologous, Vascularized and Immunocompetent Tissue Engineered Skin to Highlight Inter‐Individual Variability to Better Understand the Human Wound Healing

In vitro tissue-engineered skin models are valuable tools for dermatological research. Yet, they often fail to reproduce the complex interactions among vascular, immune, and cutaneous cells during the wound healing process. In addition, inter-individual variability response remains poorly understood, limiting our knowledge of the genetic and environmental factors that influence wound healing. This study presents a 3D autologous, vascularised, and immunocompetent Tissue Engineered Skin model (aviTES), generated using cells from the same donor to study the wound healing process. The aviTES models were injured using a 2 mm punch biopsy, and wound closure was macroscopically monitored for 7 days in the absence of any stimuli. The re-epithelialisation rate was highly reproducible within the same donor. However, wound closure differed between healthy donors (five distinct donors), highlighting individual variability. Indeed, in most cases, complete re-epithelialisation was observed within 2-4 days, but one did not close completely after 7 days. Immunofluorescence analysis revealed lymphocytes (CD45+/CD3+) migration for all donors, but no migration of CD206-positive cells or neo-angiogenesis into the wound sites. By contrast, platelet lysate treatment promoted epidermal cell migration, capillary organisation/neo-angiogenesis, and altered collagen and MMP secretion at levels that were specific to each donor, highlighting donor-specific responses to treatment. This innovative autologous skin model reproduced several key features of the human wound healing process and may represent a new tool for studying wound healing process and inter-individual variability, paving the way for advances in personalised medicine.