Vascularization strategies for bioprinting

Abstract

The desire to create tissues capable of replacing damaged or diseased organs has been a goal of the field of biomedical engineering since its inception. Over the years, in order to create these tissues, researchers have developed biomaterials, in particular water-rich hydrogels that approximate physical properties of tissues, for use as scaffolds, into which cells can be incorporated. At the cellular level, hydrogels also closely mimic the native tissue environment, permitting cell adhesion and diffusion of nutrients. More recently, the advent of 3D printing technologies has also given researchers a tool with which to accurately shape these hydrogels to anatomical needs. However, cell viability becomes adversely affected beyond a few hundred microns from a media-facing surface due to diffusion limits. Without an active circulation system, these cells often have poor viability as the rate of nutrient diffusion is unable to keep up with the metabolic requirements of the cells. In this paper, we describe two strategies we are developing to address this challenge. In the first, we designed a DLP-based continuous bioprinter combined with an extruder, using the former to rapidly print cell-laden hydrogel structures, and the latter to deposit sacrificial fibers. Removal of the sacrificial materials creates channels in the hydrogel, through which the cells can be supplied with nutrients. In the second strategy, we have developed a bioprintable granular material, which can be used to create hyper-porous structures capable of supporting cellular metabolism. These strategies allow cells to survive in the immediate aftermath of bioprinting, and provide the construct sufficient time to be vascularized.