Scalable Biofabrication of Tissue Spheroids for Organ Printing

Abstract

Organ printing technology or robotic additive biofabrication of 3D functional tissue and organ constructs is based on using tissue spheroids as building blocks. In order to bioprint human organs it is necessary to develop technology for scalable production of millions tissue spheroids. Ideally, these tissue spheroids must have standard size and shape suitable for bioprinting process. The scalable biofabrication of large volume of standard size tissue spheroids could be achieved only by maximal employment of robotics and automation technologies. The three main competing groups of emerging tissue spheroid biofabrication technologies include: i) modified handing drop method, 2) molded non-adhesive hydrogel technology and iii) digital microfluidic technologies. The comparative analysis of emerging scalable tissue spheroid biofabrication technologies has been performed. Our data indicates that all these technologies have potential for robotization and automation. The molded non-adhesive hydrogel technologies provide best outcome for standardization of tissue spheroid size. The microfluidics technology has strong advantage in accelerating of tissue spheroids biofabrication (theoretically, up to 10 000 droplets per second). New emerging approaches for biofabrication tissue spheroid using nanopatterned biomimetic surface and technologies for tissue spheroid encapsulation and functionalization will be also presented. The tissue spheroid biofabrication technologies are still evolving and represent hot area in biofabrication research. Moreover, these technologies are already subject of ongoing commercialization. Thus, it is safe to predict that scalable robotic tissue spheroid biofabricators must be integrated parts of organ biofabrication line.