Bioengineering microvascular network in led light-dermo-epidermal skin model

Abstract

The development of increasingly biomimetic human tissue analogs has been a long-standing goal in two important biomedical applications: drug discovery and regenerative medicine. In seeking to understand the safety and effectiveness of newly developed pharmacological therapies and replacement tissues for severely injured non-regenerating tissues and organs, there remains a tremendous unmet need in generating tissues with both functional complexity and scale. In this study, we propose to simultaneously apply LED visible-light source associated with photosensitizers to activate fibroblast (HDFs)-endothelial (HDECs) 3D co-cultured system in order to obtain a vascularized dermis tissue engineering model. Them, human dermal keratinocytes (HDKs) will be cultivated on the vascularized dermis equivalent to obtain a full skin model. Structure, morphology and function of micro-vessels will be evaluated by histology, immunofluorescence and protein expression. Finally, the biocompatibility of the vascularized skin substitutes with physiological, structural, and functional properties will be evaluated by in vivo subcutaneous implantation. Thus, we believe that the proposed equivalent tissue may represent an effective precursor of a new class of skin substitute of clinical interest and contribute to the understanding of skin graft vascularization and advancement of basic research in this field, especially that one has been started in our Research Group (CNET). (AU)