3D Bioprinting and Its Application to Military Medicine
Authors: Betz Jordan F , Ho Vincent B , Gaston Joel D 
Published: June 2020

Abstract

Introduction
Traditionally, tissue engineering techniques have largely focused on 2D cell culture models—monolayers of immortalized or primary cells growing on tissue culture plastic. Although these techniques have proven useful in research, they often lack physiological validity, because of the absence of fundamental tissue properties, such as multicellular organization, specialized extracellular matrix structures, and molecular or force gradients essential to proper physiological function. More recent advances in 3D cell culture methods have facilitated the development of more complex physiological models and tissue constructs; however, these often rely on self-organization of cells (bottom-up design), and the range of tissue construct size and complexity generated by these methods remains relatively limited. By borrowing from advances in the additive manufacturing field, 3D bioprinting techniques are enabling top-down design and fabrication of cellular constructs with controlled sizing, spacing, and chemical functionality. The high degree of control over engineered tissue architecture, previously unavailable to researchers, enables the generation of more complex, physiologically relevant 3D tissue constructs. Three main 3D bioprinting techniques are reviewed—extrusion, droplet-based, and laser-assisted bioprinting techniques are among the more robust 3D bioprinting techniques, each with its own strengths and weaknesses. High complexity tissue constructs created through 3D bioprinting are opening up new avenues in tissue engineering, regenerative medicine, and physiological model systems for researchers in the military medicine community.

Materials and Methods
Recent primary literature and reviews were selected to provide a broad overview of the field of 3D bioprinting and illustrate techniques and examples of 3D bioprinting relevant to military medicine. References were selected to illustrate specific examples of advances and potential military medicine applications in the 3D bioprinting field, rather than to serve as a comprehensive review.

Results
Three classes of 3D bioprinting techniques were reviewed: extrusion, droplet-based, and laser-assisted bioprinting. Advantages, disadvantages, important considerations, and constraints of each technique were discussed. Examples from the primary literature were given to illustrate the techniques. Relevant applications of 3D bioprinting to military medicine, namely tissue engineering/regenerative medicine and new models of physiological systems, are discussed in the context of advancing military medicine.

Conclusions
3D bioprinting is a rapidly evolving field that provides researchers the ability to build tissue constructs that are more complex and physiologically relevant than traditional 2D culture methods. Advances in bioprinting techniques, bioink formulation, and cell culture methods are being translated into new paradigms in tissue engineering and physiological system modeling, advancing the state of the art, and increasing construct availability to the military medicine research community.