Biosynthetic, biomimetic, and self-assembled vascularized Organ-on-a-Chip systems

Organ-on-a-Chip (OOC) devices have seen major advances in the last years with respect to biological complexity, physiological composition and biomedical relevance. In this context, integration of vasculature has proven to be a crucial element for long-term culture of thick tissue samples as well as for realistic pharmacokinetic, toxicity and metabolic modelling. With the emergence of digital production technologies and the reinvention of existing tools, a multitude of design approaches for guided angioand vasculogenesis is available today. The underlying production methods can be categorized into biosynthetic, biomimetic and self-assembled vasculature formation. The diversity and importance of production approaches, vascularization strategies as well as biomaterials and cell sourcing are illustrated in this work. A comprehensive technological review with a strong focus on the challenge of producing physiologically relevant vascular structures is given. Finally, the remaining obstacles and opportunities in the development of vascularized Organ-on-a-Chip platforms for advancing drug development and predictive disease modelling are noted.