Advances in Extrusion 3D Bioprinting: A Focus on Multicomponent Hydrogel‐Based Bioinks

Abstract

Abstract3D bioprinting involves the combination of 3D printing technologies with cells, growth factors and biomaterials, and has been considered as one of the most advanced tools for tissue engineering and regenerative medicine (TERM). However, despite multiple breakthroughs, it is evident that numerous challenges need to be overcome before 3D bioprinting will eventually become a clinical solution for a variety of TERM applications. To produce a 3D structure that is biologically functional, cell‐laden bioinks must be optimized to meet certain key characteristics including rheological properties, physico‐mechanical properties, and biofunctionality; a difficult task for a single component bioink especially for extrusion based bioprinting. As such, more recent research has been centred on multicomponent bioinks consisting of a combination of two or more biomaterials to improve printability, shape fidelity and biofunctionality. In this article, multicomponent hydrogel‐based bioink systems are systemically reviewed based on the inherent nature of the bioink (natural or synthetic hydrogels), including the most current examples demonstrating properties and advances in application of multicomponent bioinks, specifically for extrusion based 3D bioprinting. This review article will assist researchers in the field in identifying the most suitable bioink based on their requirements, as well as pinpointing current unmet challenges in the field.

Printability and Shape Fidelity of Bioinks in 3D Bioprinting

“…These molecules, upon exposure to light, produce reactive species that trigger the polymerization process. 57 , 108 − 112 Most photo-cross-linkable systems rely on ultraviolet A (UV-A) and visible light irradiation at wavelengths that do not directly cause significant DNA damage. 113 , 114 These approaches make use of commonly used photoinitiators and photosensitizers (e.g., Irgacure 2959, 115 , 116 lithium phenyl-2,4,6-trimethylbenzoylphosphinate, 116 , 117 Eosin Y, 118 ruthenium/sodium persulfate, 119 and rose Bengal 120 ).…”

Current Trends in In Vitro Modeling to Mimic Cellular Crosstalk in Periodontal Tissue

“…Most of the published bioprinted models were manufactured using the microextrusion method, where rods of cell-laden hydrogel are deposited in a computer-controlled manner. [118] The reasons for the frequent use of extrusion-based bioprinting include its simplicity, the ease of operation of the printers, and finally the availability of a great number of different extrusionbased bioprinters on the market (Figure 8A-E). So far, there has been one study available in which the microextrusion bioprinting technique was applied to investigate the basic cellular response of printed periodontal ligament cells.…”

Natural Biomaterials and Their Use as Bioinks for Printing Tissues

“…A bioink should have and maintain similar properties to the targeted tissues, including: (i) physico-mechanical properties; and (ii) biological properties, to be considered biofunctional [ 24 , 43 , 44 ]. Not only does the bioink have to maintain cell viability, but it must also be printable.…”

“…Accordingly, bioinks may be modified depending on the printer being used and the target tissue. For all these properties to be achieved, especially for extrusion-based bioprinting, a mix of two or more biomaterials is usually required [ 43 , 45 ]. Multicomponent bioinks are also often superior to those made up of solely one biomaterial as single component bioinks usually lack sufficient biocompatibility and high mechanical and functional requirements to form biomimicry tissues [ 45 ].…”