Recent Advances in Bioink Design for 3D Bioprinting of Tissues and Organs

Abstract

There is a growing demand for alternative fabrication approaches to develop tissues and organs as conventional techniques are not capable of fabricating constructs with required structural, mechanical, and biological complexity. 3D bioprinting offers great potential to fabricate highly complex constructs with precise control of structure, mechanics, and biological matter [i.e., cells and extracellular matrix (ECM) components]. 3D bioprinting is an additive manufacturing approach that utilizes a "bioink" to fabricate devices and scaffolds in a layer-by-layer manner. 3D bioprinting allows printing of a cell suspension into a tissue construct with or without a scaffold support. The most common bioinks are cell-laden hydrogels, decellulerized ECM-based solutions, and cell suspensions. In this mini review, a brief description and comparison of the bioprinting methods, including extrusion-based, droplet-based, and laser-based bioprinting, with particular focus on bioink design requirements are presented. We also present the current state of the art in bioink design including the challenges and future directions.

Keywords: additive manufacturing; biofabrication; cell printing; extracellular matrix; hydrogel; regenerative medicine; tissue engineering.

Figure 1

3D bioprinting techniques for bioprinting of tissues and organs. Figure reproduced with permission from Miller and Burdick (2016). Copyright 2016, American Chemical Society.

Figure 2

(i) 3D printed constructs in various forms (a,b) using poly(ethylene glycol)–alginate–nanoclay hydrogels. Red food dye was incorporated into some of the bioink formulations for visibility. Live/dead assay of cells (c) in a collagen infused mesh from (b). Reprinted with permission from Hong et al. (2015). Copyright 2015, John Wiley and Sons. (ii) Tissue construct printed from decellularized extracellular matrix (dECM) (a), SEM images of hybrid constructs from dECM supported with polycaprolactone framework (b,c), and fluorescent images of cells (d). Scale bars are 5 mm for (a), 400 µm for (b,c), and 100 µm for (d). Adapted with permission from Pati et al. (2014). Copyright 2014, Nature Publishing Group. (iii) Cell aggregate (500-µm average diameter) configurations in simulations (A,B,K,L) and experiments. C–J correspond to cell aggregates embedded in a neurogel with RGD fragments (C,D) and collagen gels of concentration 1.0 mg/ml (E,F), 1.2 mg/ml (G,H), and 1.7 mg/ml (I,J). Figure adapted with permission from Jakab et al. (2004). Copyright 2004, National Academy of Sciences.