Candidate Bioinks for Extrusion 3D Bioprinting—A Systematic Review of the Literature

Abstract

Purpose: Bioprinting is becoming an increasingly popular platform technology for engineering a variety of tissue types. Our aim was to identify biomaterials that have been found to be suitable for extrusion 3D bioprinting, outline their biomechanical properties and biocompatibility towards their application for bioprinting specific tissue types. This systematic review provides an in-depth overview of current biomaterials suitable for extrusion to aid bioink selection for specific research purposes and facilitate design of novel tailored bioinks.Methods: A systematic search was performed on EMBASE, PubMed, Scopus and Web of Science databases according to the PRISMA guidelines. References of relevant articles, between December 2006 to January 2018, on candidate bioinks used in extrusion 3D bioprinting were reviewed by two independent investigators against standardised inclusion and exclusion criteria. Data was extracted on bioprinter brand and model, printing technique and specifications (speed and resolution), bioink material and class of mechanical assessment, cell type, viability, and target tissue. Also noted were authors, study design (in vitro/in vivo), study duration and year of publication.Results: A total of 9,720 studies were identified, 123 of which met inclusion criteria, consisting of a total of 58 reports using natural biomaterials, 26 using synthetic biomaterials and 39 using a combination of biomaterials as bioinks. Alginate (n = 50) and PCL (n = 33) were the most commonly used bioinks, followed by gelatin (n = 18) and methacrylated gelatin (GelMA) (n = 16). Pneumatic extrusion bioprinting techniques were the most common (n = 78), followed by piston (n = 28). The majority of studies focus on the target tissue, most commonly bone and cartilage, and investigate only one bioink rather than assessing a range to identify those with the most promising printability and biocompatibility characteristics. The Bioscaffolder (GeSiM, Germany), 3D Discovery (regenHU, Switzerland), and Bioplotter (EnvisionTEC, Germany) were the most commonly used commercial bioprinters (n = 35 in total), but groups most often opted to create their own in-house devices (n = 20). Many studies also failed to specify whether the mechanical data reflected pre-, during or post-printing, pre- or post-crosslinking and with or without cells.Conclusions: Despite the continued increase in the variety of biocompatible synthetic materials available, there has been a shift change towards using natural rather than synthetic bioinks for extrusion bioprinting, dominated by alginate either alone or in combination with other biomaterials. On qualitative analysis, no link was demonstrated between the type of bioink or extrusion technique and the target tissue, indicating that bioprinting research is in its infancy with no established tissue specific bioinks or bioprinting techniques. Further research is needed on side-by-side characterisation of bioinks with standardisation of the type and timing of biomechanical assessment.

Biofabrication of Collagen Tissue-Engineered Blood Vessels with Direct Co-Axial Extrusion

“…Gelatin microparticle formation was developed following a previously published method [ 14 ]. First, a solution containing a final concentration of 2% ( w/v ) gelatin Type B (Sigma-Aldrich, Darmstadt, Germany), 0.25% ( w/v ) Pluronic F-127 (Sigma-Aldrich, Darmstadt, Germany) and 0.1% ( w/v ) gum arabic (Sigma-Aldrich, Darmstadt, Germany) in 1 L of 50% ( v/v ) ethanol (PanReac AppliChem, Schaffhausen, Switzerland) was heated to 45 °C.…”

“…At the same time, this method proved to be successful for the extrusion of cells without compromising their viability and proliferative capacity. In order to develop collagen TEBVs with co-axial extrusion, there is the need to combine it with other biomaterials with instantly crosslinking properties to provide structural support when being extruded, as collagen itself is not self-supportive [ 14 , 15 ]. In this regard, the most used is alginate due to its instant gelling ability when in contact with divalent ions [ 16 ].…”

Protocol for printing 3D neural tissues using the BIO X equipped with a pneumatic printhead

“…A variety of synthetic and natural biomaterials exist that have been verified for extrusion bioprinting and should be compatible with this protocol. The bioink design should consider the mechanical, rheological, and crosslinking properties of the biomaterial components utilized ( Benwood et al., 2021 ; Tarassoli et al., 2021 ; Yilmaz et al., 2021 ).…”

A Guide to Polysaccharide-Based Hydrogel Bioinks for 3D Bioprinting Applications

“…The developments in the field of bioinks for 3D bioprinting applications have been the theme of several appraisals [ 18 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ]. Specifically, the progress over the last two decades was reviewed by Pedroza-Gonzalez et al [ 39 ], who provided a systematic analysis of more than 390 original papers from 2000 to 2019.…”