Title : Pre-vascularized skin model in vitro
Abstract:
Animal models have been used for decades in various physiological, pathophysiological, pharmaceutical, toxicological and other biomedical studies. However, significant obstacles of these models are ethical issues, considerable costs, and limited translatability of study outcomes to actual human diseases. Herein, developing 3D in vitro tissue models, using knowledge of stem cell biology, biomaterials, and tissue engineering, has been considered as a potential replacement for animal models. A pre-vascularized dermal- epidermal construct could serve not only as an in vitro skin tissue model, but also as a skin substitute for repair and regeneration of skin defects. Human dermal fibroblasts (NHDFs) and human adipose stem cells (ASCs) have very similar cell markers and properties. NHDFs have been widely used to construct skin grafts, and ASCs have recently become popular for cell therapy applications due to their stem cell properties and convenient resources. In this study, electrospun polycaprolactone nanofibrous membranes were used as supportive structures for skin constructs, and these membranes were further modified with fibrin and fibronectin to increase their attractiveness for cell adhesion and growth. Different densities of NHDFs and ASCs were seeded on the fibronectin-coated nanofibrous membranes, and then covered with fibronectin-enriched collagen hydrogels loaded with human umbilical vein endothelial cells (HUVECs). The initial results showed that both constructs formed capillaries after 21 days in culture. However, more branched and longer capillaries and with denser tubular capillary-like networks were formed in ASC-based skin constructs compared to NHDFs-based skin constructs. The properties of these two pre-vascularized constructs will then be further analyzed. To construct more simulated skin constructs, ASCs-based NHDFs with HUVECs skin constructs were fabricated, and keratinocytes will be the last added to reconstruct the epidermis for future skin and transplantation applications.
Audience Take Away Notes:
- Higher amount of NHDFs or ASCs with HUVECs form more capillaries
- ASCs-based skin constructs form better capillary networks
