Microfluidic-Based 3D Bioprinting of Vascular Endothelial Networks Using Alginate-Collagen Based Biomaterials

Despite recent advances in 3D bioprinting technologies, the biofabrication of complex vascular network architectures has remained a key challenge in engineering tissues. In this study, we leveraged a novel microfluidic based 3D bioprinting technology and alginate-collagen type I (AGC)-based bioinks, to develop a 3D bioprinting strategy to enable the biofabrication of complex vascular networks comprised of SV40 transformed adult rat brain endothelial cell (SV-ARBEC)-laden hydrogel rings with mechanical properties relevant for neurovascular tissue engineering applications. The bioprinted SV-ARBECs retained high cellular viability, at high tissue level cell densities, and formed spontaneous endothelial vascular networks reminiscent of anisotropic tissue-like structures. The vascular network formation was accompanied by extracellular matrix remodeling (ECM) remodelling, evaluated by second harmonic generation (SHG) microscopy, confirming sequential SV-ARBEC mediated collagen type I fiber deposition and reorganization. This novel 3D microfluidic bioprinting technology and biocompatible AGC hydrogel fiber rings enabled robust SV-ARBEC angiogenesis and vascular network formation which are key towards advancing applications in vascular research and development, disease modeling, drug discovery and tissue engineering applications.