Sacrificial Templating for Accelerating Clinical Translation of Engineered Organs.

Abstract

Transplantable engineered organs could one day be used to treat patients suffering from end-stage organ failure. Yet, producing hierarchical vascular networks that sustain the viability and function of cells within human-scale organs remains a major challenge. Sacrificial templating has emerged as a promising biofabrication method that could overcome this challenge. Here, we explore and evaluate various strategies and materials that have been used for sacrificial templating. First, we emphasize fabrication approaches that use highly biocompatible sacrificial reagents and minimize the duration that cells spend in fabrication conditions without oxygen and nutrients. We then discuss strategies to create continuous, hierarchical vascular networks, both using biofabrication alone and using hybrid methods that integrate biologically driven vascular self-assembly into sacrificial templating workflows. Finally, we address the importance of structurally reinforcing engineered vessel walls to achieve stable blood flow in vivo, so that engineered organs remain perfused and functional long after implantation. Together, these sacrificial templating strategies have the potential to overcome many current limitations in biofabrication and accelerate clinical translation of transplantable, fully functional engineered organs to rescue patients from organ failure.