Goat tendon collagen-human fibrin hydrogel for comprehensive parametric evaluation of HUVEC microtissue-based angiogenesis

The cell and extracellular matrix (ECM) interactions play a very important role during angiogenesis. Remodeling of the extracellular matrix along with pro-angiogenic/anti-angiogenic factors, and matrix-degrading proteases, accounts for endothelial cell growth, migration, and tube formation. However, for studying angiogenesis, only limited and expensive biomaterials are available. Despite being biocompatible, inexpensive, and easy availability; the potential of goat tendon collagen (GTC) has never been explored for vascular tissue engineering applications. Hence, the current investigation was focused on evaluating GTC as an alternative matrix for HUVEC microtissue-based angiogenesis. HUVEC microtissues (MTs), synthesized via hanging drop method, were subjected to angiogenesis in GTC-human fibrin (HF) hydrogels. Sprouting tip cells originated from the MTs within 24 h. Further, comprehensive in vitro study and in vivo validation revealed that, endothelial media with FBS and growth factors, 24 h old HUVEC MTs of 500 cells, seeded at 200 aggregates/cm3 in GTC-HF gel of 100 Pa elastic modulus, resulted in most optimal angiogenesis with intact lumen that was stable up to a week, without any supporting cells. Although early to predict, GTC-HF matrix may serve as a potential ECM for engineering complex and functional tissues of clinical relevance.