We introduce a novel automated rapid prototyping method (organ printing) that allows engineering fully biological three-dimensional custom-shaped tissue and organ modules. In this technology bio-ink units (multicellular aggregates) composed of single or several cell types together with supporting material are delivered by special printers. Printing of the bio-ink units (controlled by architectural software) is carried out according to a design template, consistent with the geometry and composition of the desired organ module. Structure formation occurs by the post-printing fusion of the discrete bio-ink units. When the bio-ink units contain more than one cell type, fusion is accompanied by sorting of the cells into the physiologically relevant pattern. Thus structure formation takes place through self-assembly processes akin to those utilized in early embryonic morphogenesis. We demonstrate the technology by detailing the construction of tubular organ modules. Vascular grafts and nerve grafts are examples of such organ modules. Spherical and cylindrical bio-ink units have been employed to build fully biological linear and branching vascular tubular conduits and multiluminal nerve grafts. Upon perfusion in a bioreactor the constructs achieved desirable biomechanical and biochemical properties that allowed implantation into animal models.
Despite these successes, building functional full organs, such as liver, kidney, heart by bioprinting or by any other tissue or organ engineering technology is not an imminent solution for the chronic shortage of donor organs. Instead of solely concentrating on organs recent bioprinting activity has focused rather on the building of anatomically correct, functional tissues that could be employed for drug screening and development. Such tissues built from human cells are being employed to interface early animal trials with human clinical trials in the drug development process. With increasing complexity such tissues could eventually lead to the complete elimination of animal trials and more relevant models for drugs designed for humans, resulting in significant savings and responding to the growing concern about harm caused to animals. As such tissues are prepared from autologous sources they open the door to the ultimate patient tailored drug development process: multiple identical copies of the engineered tissue can be used for different formulations of the drug until the optimal one for the patient if found. In addition, these tissues can also be used for toxicology assays, again in a patient tailored manner further potentially mitigating the risks, associated with adverse side effects.
In summary, our results show that the printing of conveniently prepared cellular units is feasible and represents a promising tissue and organ engineering technology with multiple applications of great significance.