Progress in scaffold-free bioprinting for cardiovascular medicine

Abstract

Biofabrication of tissue analogues is aspiring to become a disruptive technology capable to solve standing biomedical problems, from generation of improved tissue models for drug testing to alleviation of the shortage of organs for transplantation. Arguably, the most powerful tool of this revolution is bioprinting, understood as the assembling of cells with biomaterials in three-dimensional structures. It is less appreciated, however, that bioprinting is not a uniform methodology, but comprises a variety of approaches. These can be broadly classified in two categories, based on the use or not of supporting biomaterials (known as "scaffolds," usually printable hydrogels also called "bioinks"). Importantly, several limitations of scaffold-dependent bioprinting can be avoided by the "scaffold-free" methods. In this overview, we comparatively present these approaches and highlight the rapidly evolving scaffold-free bioprinting, as applied to cardiovascular tissue engineering.

Keywords: Kenzan method; bioprinting; cardiovascular tissue engineering; cell spheroids; scaffold-free biofabrication.

Figure 1

Scaffold‐free bioprinting of a vascular graft on the Regenova bioprinter. A, Frontal view of the robot, together with its controlling computer. B, Virtual design of the spheroids positioning in the tube. C, Actual construct demonstrating surgical robustness for implantation (modified with permission from Itoh et al 51)

Figure 2

Schematic of biomaterial‐free bioprinting of a cardiac patch. A, Cells (CM, FB, EC) are aggregated in ultra‐low attachment 96‐well plates to form spheroids. B, The desired 3D structure is designed using computer software. C, The robot picks up individual spheroids using vacuum suction and loads them onto a needle array. D, Spheroids are allowed to fuse. The 3D bioprinted cardiac tissue is then removed from the needle array and further cultured to allow the needle holes to be resorbed (reproduced with permission from Ong et al 56)