Vascularization in 3D printed tissues: emerging technologies to overcome longstanding obstacles

Abstract

This review paper endeavors to provide insights into the emergence of 3D bioprinting as an alternative to longstanding tissue fabrication techniques primarily through an overview of recent advances in bioprinting vascularized tissues. Bioprinting has promise in resolving many issues that persist within tissue engineering including: insufficient perfusion of nutrients to tissue constructs, high rates of cell necrosis, and lack of cell proliferation and proper differentiation. These issues stem from a lack of proper angiogenesis, a primary challenge that remains to be overcome in tissue engineering. This review will discuss emerging 3D bioprinting techniques (such as inkjet printing, extrusion printing, and stereolithography, among others) that have been specially adapted to enhance and improve the vascularization process. Compatible bioinks are also discussed as they are vital to the 3D bioprinting process by allowing for the building of matrices that encourage vasculature to develop, survive, and prosper under physiological flow rates. Currently, these 3D bioprinting techniques have succeeded in increasing the long-term viability of thick tissues, generated luminal structures needed for vascularization, and allowed for differentiation factors to reach cells deep within thick constructs (~1 cm). While great progress has been made, 3D bioprinting continues to have deficits in high-resolution printing, viability at prolonged time scales and larger thicknesses required for organ transplantation, and the mechanical stability needed for long-term organ functioning. Nonetheless, the recent developments in the vascularization of tissues through bioprinting techniques are paving the way for lab-grown tissues and organs, which could have uses in transplants, in vitro drug testing, and enhancing the current knowledge of organ function.