A first vascularized skin equivalent as an alternative to animal experimentation

Abstract

Tissue-engineered skin equivalents mimic key aspects of the human skin and can thus be employed as wound coverage for large skin defects or as in vitro test systems as an alternative to animal models. However, current skin equivalents lack a functional vasculature, limiting clinical and research applications. This study demonstrates the generation of a vas­cularized skin equivalent with a perfused vascular network by combining a biological vascularized scaffold (BioVaSc) based on a decellularized segment of porcine jejunum and a tailored bioreactor system. The BioVaSc was seeded with human fibroblasts, keratinocytes, and human microvascular endothelial cells. After 14 days at the air-liquid interface, hematoxylin & eosin and immunohistological staining revealed a specific histological architecture representative of the human dermis and epidermis, including a papillary-like architecture at the dermal-epidermal-junction. The formation of the skin barrier was measured non-destructively using impedance spectroscopy. Additionally, endothelial cells lined the walls of the formed vessels that could be perfused with a physiological volume flow. Due to the presence of a complex in vivo-like vasculature, the here shown skin equivalent has the potential to be used for skin grafting and represents a sophisticated in vitro model for dermatological research.