(570c) Vascularized Multi-Tissue Platform – 3D Bioprinting an Organ Model in Vitro

There is a growing need for functional in vitro models of tissue and organs which can be used in regenerative medicine to supplement or restore lost function and as next-generation drug evaluation platforms to screen candidate compounds in organ-mimic cultures. Specifically, of interest to our group are models of vascular tissues, as they can be applied to a range of organs and conditions that are responsible for exorbitant healthcare and economic burden in the US and globally. In recent years, 3D bioprinting has emerged as a promising solution to address the need for consistent and reproducible biomanufacturing of tissues and organ constructs. While there have been significant advances in the field of tissue bioprinting, such as enhanced print resolution and better understanding of 3D culture parameters, their applications are limited by the lack of robust, guided, and reproducible vascularization and perfusion. We present here a perfusable vascular tissue platform based on the state-of-the-art 3D bioprinting and additive manufacturing technologies that allow for the generation of complex in vitro multi-cellular tissue analogues to model in vivo structures/functions. We generated model vasculature networks using cyto-GFP HUVECs in various geometries and sizes, ranging from 0.5 to 2 mm, using hybrid bioprinting and 3D printing techniques. Our constructs, with thickness of 6 mm, were maintained under biomimetic flow conditions for 14 days. AlamarBlue assay and fluorescence microscopy showed significant increase in cell viability (metabolic activity) throughout the 14-day perfusion period. The HUVECs formed an endothelium on the surface of printed channels and initiated new capillary formation. Further, when compared to static conditions, the perfused constructs showed enhanced diffusion, based on non-toxic dye gradient measurement, which was also reflected in their metabolic activity readouts. Taken together, our results address the need for reliable perfusion in biomimetic vascularized tissue constructs which is a critical requirement for generation of clinically relevant bioengineered implants.