Biomechanical factors in three-dimensional tissue bioprinting

Abstract

3D bioprinting techniques have shown great promise in various fields of tissue engineering and regenerative medicine. Yet, creating a tissue construct that faithfully represents the tightly regulated composition, microenvironment, and function of native tissues is still challenging. Among various factors, biomechanics of bioprinting processes play fundamental roles in determining the ultimate outcome of manufactured constructs. This review provides a comprehensive and detailed overview on various biomechanical factors involved in tissue bioprinting, including those involved in pre, during, and post printing procedures. In preprinting processes, factors including viscosity, osmotic pressure, and injectability are reviewed and their influence on cell behavior during the bioink preparation is discussed, providing a basic guidance for the selection and optimization of bioinks. In during bioprinting processes, we review the key characteristics that determine the success of tissue manufacturing, including the rheological properties and surface tension of the bioink, printing flow rate control, process-induced mechanical forces, and the in situ cross-linking mechanisms. Advanced bioprinting techniques, including embedded and multi-material printing, are explored. For post printing steps, general techniques and equipment that are used for characterizing the biomechanical properties of printed tissue constructs are reviewed. Furthermore, the biomechanical interactions between printed constructs and various tissue/cell types are elaborated for both in vitro and in vivo applications. The review is concluded with an outlook regarding the significance of biomechanical processes in tissue bioprinting, presenting future directions to address some of the key challenges faced by the bioprinting community.

FIG. 1.

Schematic representation of the main 3D bioprinting strategies, including inkjet (left), extrusion (middle), and laser-based (right) bioprinting.

FIG. 2.

Rheological properties of hydrogels and their significance in tissue bioprinting. (a) Schematic of a plate-and-cone rheometer. (b) Different types of flow behavior for hydrogels.

FIG. 3.

Schematic of printed filaments. (a) Surface tension-driven bioink droplets at the outlet of the needle, (b) continuous filament after leaving the outlet the needle due to yield stress of the bioink, and (c) contact angle of the printed filament.

FIG. 4.

Examining cell deformation and damages under mechanical forces during 3D bioprinting. (a) Schematic illustration of the 3D bioprinting process and the mechanical stresses involved. (b) and (c) Schwann cell membrane rupture and damage in bioprinting with applied bioprinting pressures of 100 kPa (b) and 400 kPa (c). (d) and (e) Live/dead assay of fibroblasts under no shearing (d) and shearing [(e), 1700 Pa]. (f) Short-term and long-term impact of different bioprinting-induced shear stress levels on human mesenchymal stem cell (MSC) viability and proliferation. Scale bar represents 100 μm. (b) and (c) Reproduced with permission from Ning et al., ACS Biomater. Sci. Eng. 4, 3906 (2018). Copyright 2018 American Chemical Society. (d) and (e) Reproduced with permission from Ning et al., Tissue Eng., Part C 22, 652 (2016). Copyright 2016 Mary Ann Liebert. (f) Reproduced with permission from Blaeser et al., Adv. Healthcare Mater. 5, 326 (2016). Copyright 2016 John Wiley and Sons.

FIG. 5.

In situ cross-linking in 3D bioprinting. (a) Thermal cross-linking; (b) cross-linking based on atomized agent spraying; (c) the use of a cross-linking medium; and (d) photopolymerization either after bioink deposition or via a light-permeable needle before extruding out.

FIG. 6.

Embedded bioprinting technique using a suspension bath.

FIG. 7.

Approaches and devices used for biomechanical assessment of printed hydrogel constructs.