A Demonstration of Bioprinting Thick Tissue that Incorporates Small-Scale Vasculature

3-D bioprinting is a form of rapid prototyping adapted to the tissue engineering industry. Printers assemble tissues from ink containing cells and supporting materials of various types. Given a suitable recipe, the result is a functional tissue quite close to the real thing in structure and function. The interesting part of this open access paper is not that the team bioprinted small-scale model hearts as their proof of concept, given that these are not fully functional heart tissues capable of the electrical coordination required to exhibit a heart beat, and nor is it that they used materials personalized to a specific patient. Rather, it is that they demonstrate the ability to bioprint networks of small blood vessels sufficient to support the interior cells of a thick tissue.

This is an important advance, even given that it is not the full microvascular networks of capillaries found in natural tissue. This matter of blood vessels is a major challenge in the tissue engineering community. Cells need a supply of blood in order to survive, and that supply must be carried by blood vessels for any distance much over a millimeter. Finding a reliable way to incorporate blood vessel networks into tissues is the primary roadblock holding back construction of replacement organs, and it is why so much work today is focused on the production of tiny, thin organoid tissue sections.

Generation of thick vascularized tissues that fully match the patient still remains an unmet challenge in cardiac tissue engineering. Here, a simple approach to 3D-print thick, vascularized, and perfusable cardiac patches that completely match the immunological, cellular, biochemical, and anatomical properties of the patient is reported. To this end, a biopsy of an omental tissue is taken from patients. While the cells are reprogrammed to become pluripotent stem cells, and differentiated to cardiomyocytes and endothelial cells, the extracellular matrix is processed into a personalized hydrogel. Following, the two cell types are separately combined with hydrogels to form bioinks for the parenchymal cardiac tissue and blood vessels.

In recent years, the strategy of 3D tissue printing evolved, allowing the creation of vasculature within hydrogels. However, in most of the studies, the endothelial cells (ECs) that form the blood vessels were printed without the parenchymal tissue, which was later on casted on top of the vessels. In other pioneering works, the researchers were able to print ECs together with thin surrounding tissues. However, the obtained tissues were not thick, the ECs did not form open blood vessels and perfusion through them was not demonstrated. Different strategies include printing of the parenchymal tissue with open, a-cellular channels in between, followed by external perfusion of ECs to form the blood vessels. Finally, decellularized hydrogels were also used for printing nonvascularized tissues. Therefore, to the best of our knowledge, the aforementioned studies did not demonstrate printing of a full, thick vascularized patch in one step.

Here, we report on the development and application of advanced 3D printing techniques using the personalized hydrogel as a bioink. In this strategy, when combined with the patient's own cells, the hydrogel may be used to print thick, vascularized, and perfusable cardiac patches that fully match the immunological, biochemical and anatomical properties of the patient. Furthermore, we demonstrate that the personalized hydrogel can be used to print volumetric, freestanding, cellular structures, including whole hearts with their major blood vessels

Link: https://doi.org/10.1002/advs.201900344