Application of 3D bioprinting in the prevention and the therapy for human diseases

Abstract

Rapid development of vaccines and therapeutics is necessary to tackle the emergence of new pathogens and infectious diseases. To speed up the drug discovery process, the conventional development pipeline can be retooled by introducing advanced in vitro models as alternatives to conventional infectious disease models and by employing advanced technology for the production of medicine and cell/drug delivery systems. In this regard, layer-by-layer construction with a 3D bioprinting system or other technologies provides a beneficial method for developing highly biomimetic and reliable in vitro models for infectious disease research. In addition, the high flexibility and versatility of 3D bioprinting offer advantages in the effective production of vaccines, therapeutics, and relevant delivery systems. Herein, we discuss the potential of 3D bioprinting technologies for the control of infectious diseases. We also suggest that 3D bioprinting in infectious disease research and drug development could be a significant platform technology for the rapid and automated production of tissue/organ models and medicines in the near future.

Fig. 1

Schematic drawing of the traditional vaccine/therapeutics discovery pipeline and the possibilities of retooling with 3D bioprinting technologies (gray boxes)

Fig. 2

Schematic diagrams of 3D bioprinting technologies. a Extrusion-based bioprinting, b FRESH-based bioprinting, c microfluidic chip-assisted bioprinting, d laser-induced forward transfer (LIFT), e stereolithography (STL), f digital light processing (DLP), g inkjet-based bioprinting

Fig. 3

Advanced in vitro models used in research of infectious disease to identify the infection mechanisms and the effective vaccines/therapeutics

Fig. 4

Microfluidic-based human organs-on-chips applied in the study of infectious diseases. a Liver-on-a-chip for the study of hepatitis B virus (HBV) infection. Adapted from Ortega-Prieto et al. b Gut-on-a-chip for the study of Coxsackie B1 Virus (CVB1) infection. Adapted from Villenave et al. c Vascular endothelium barrier-on-a-chip for evaluating the effect of Ebola virus-like particle (VLP) on vascular integrity. White arrows indicate remodeling of F-actin. Adapted from Junaid et al.

Fig. 5

3D bioprinted in vitro models of human tissues and organs. a 3D cell-printed skin model composed of epidermis, dermis, hypodermis, and vascular channel. Stained images using representative markers of each layer: b epidermis, c dermis, d vascular channel, and e hypodermis (scale bars, 50 µm). Reproduced with permission from Kim et al. f 3D bioprinting of transparent corneal tissue via the alignment of collagen fibers within the nozzle during bioink extrusion. g Second-harmonic generation (SHG) images of shear-aligned collagen using each nozzle. (scale bar, 20 μm). h Distributions of collagen orientations at different azimuthal angles. Reproduced with permission from Kim et al. i Schematic diagram of the spinal cord illustrating gray matter and white matter boundaries and the 3D bioprinting process. Reproduced with permission from Joung et al. j Coaxial printing of monolayer and bilayer structures in complex hollow tubes. The schematic represents monolayer (I), bilayer (II), and fine-tuning between monolayer to bilayer at defined intervals in the complex hollow (III) tubes for renal tubular tissue. k A convoluted hollow tube with a transitional region between monolayer and bilayer structures. (scale bars, 1 mm). l Schematic representation of the glomerulus and proximal tubule in native kidney tissue. m 3D bioprinting of complex renal tubular structures. (scale bar, 500 μm). Reproduced with permission from Singh et al.

Fig. 6

Applications of 3D bioprinting for manufacturing of vaccines, therapeutics, and delivery systems