Anna Fritschen (Darmstadt, DE), Sebastian Scholpp (Darmstadt, DE), Mariana Acedo Mestre (Darmstadt, DE), Philipp Richthof (Darmstadt, DE), Prof. Dr. Andreas Blaeser (Darmstadt, DE)
Abstract text (incl. figure legends and references)
Introduction & Objectives
Biomimetic Organs-on-a-Chip are key for advanced drug screening and research, but require complex 3D arrangements of multiple cell types representing organ-specific cells, connective tissue, and vasculature. Combined with suitable bioinks, drop-based 3D-bioprinting is a powerful tool to create these models.
This work includes an in-depth analysis of various bioinks and cultivation protocols for a print process of a multicellular and vascular tissue model on a microfluidic chip. To demonstrate the feasibility of the approach, HepG2 islets are embedded in a microvascular bed of HUVEC and HDF.
Materials & Methods
The microfluidic chip was designed in an open lid setup enabling the direct bioprinting into the cultivation chamber. Bioink formulations comprising agarose, collagen, and gelatin were investigated for the fabrication of HepG2 cell islands, while fibrin was selected as vascular bed promoting bioink. The gels were characterized regarding rheology, microstructure and cell behavior. In parallel, a medium formulation that supports growth of all three cell types was identified using proliferation assays. The printability of the selected bioinks was monitored by various imaging technologies both in-flight and post-printing. Finally, the tissue model was printed, cultured under perfusion and vascular network formation monitored.
Results & Conclusion
Two bioinks – a collagen-gelatin blend and agarose - were identified for the HepG2 islets as suitable considering printability, gel structure and cellular behavior. HUVECs and HDF mixed in 10 mg/ml fibrin at a total cell concentration of 5 Mio/ml resulted in vascular network formation throughout the chip and around the HepG2 islets. By combining both bioinks, we achieved a reproducible, fast and scalable multi-material print process, demonstrating the high versatility of combining microfluidics and 3D-bioprinting and its potential for the future fabrication of vascularized tissue models.