A three-dimensional model for analysis and control of phase change phenomena during 3D printing of biological tissue

Abstract

Three-dimensional (3D) bioprinting is one of the fastest advancing and most promising techniques for tissue engineering. However, despite numerous developments in 3D bioprinting, issues of size scalability remain. Two primary factors limiting the scale of printable objects are the structural properties of the bioinks and the unsustainable time it takes to bioprint large structures. Freezing has been proposed as a possible solution to both, improving the mechanical properties of the soft aqueous hydrogel bioinks and reducing the adverse effects of cell metabolism with the lowered temperature. In addition, it eases the longer-term cryopreservation of the larger tissue constructs as they can be frozen element by element at faster (more preferable) and uniform cooling rates during printing rather than whole after 3D bioprinting. However, for freezing to be a feasible 3D bioprinting technique, there is a need to better understand the effect of phase change during printing on biological matter. This can be done by rigorous experimentation or alternatively, using mathematical tools and models. Though, most techniques of 3D printing are inherently thermal processes, limited thermal analysis has been done on extrusion-based (fused deposition modeling) printing processes to characterize thermal effects. This paper introduces a model for analysis of the thermal phase change process during the 3D bioprinting of biological matter at low temperature. The model was developed and experimentally validated for an extrusion-based printing process of aqueous biological material. It was used to investigate the conditions under which a constant freezing rate could be achieved during multilayer printing and the size limitations in conduction dependent freezing from a cold surface during printing. Overall, this model could be a useful tool for the design and control of the 3D printing protocols.