For injectable hydrogels, the shear thinning properties of hydrogels among the essential properties, like for bioinks

For injectable hydrogels, the shear thinning properties of hydrogels among the essential properties, like for bioinks. It GB-88 also provides a platform to make a heterogeneous construct of different cells and bioinks [4]. ATF3 The first generation of 3D printing was used to construct biomaterial scaffolds which were then seeded with cells to make tissue constructs. Seeding of the scaffolds leads to non-uniform distribution of cells within the scaffold [5,6]. For homogenous distribution of cells in the construct/scaffold as well as to make heterogeneous platforms with multiple cell types with a restricted cell niche, cell-laden biomaterial GB-88 constructs were developed [7,8,9,10]. Therefore, bioinks which could encapsulate cells to support such construction became an important field for tissue development. Many printing technologies like light-mediated stereolithography (SLA) [11,12], selective laser sintering (SLS) of polymeric and metallic powders [13], fused deposition modelling (FDM) of synthetic thermoplastics [14,15], inkjet printing [16] and direct extrusion have been employed for scaffold printing [17]. In case of SLS, SLA and FDM, the processes involve high temperature, powder beds, solvent baths and high energy radiations which make them unsuitable for bioprinting of cell laden constructs. Inkjet and extrusion printing are the two major printing technologies which can print cell-laden constructs under physiological conditions. Inkjet printing has been widely used for 3D printing of cell-laden constructs due to its ability to provide good cell viability in comparison to micro-extrusion printing, but bioprinting of viscous bioinks is relatively challenging. This led researchers to employ micro-extrusion printing to print viscous bioinks. Micro-extrusion printing provides a platform to print cell-laden constructs efficiently and in a controllable manner under physiological conditions [18]. In micro-extrusion printing, desired biomaterial structures can be built by dispensing biomaterials through nozzles or needles connected to cartridges loaded with ink. Multiple cartridges can be loaded in the printer to print heterogeneous structures. For bioprinting of cell laden constructs, cells are blended with bioink. Bioink is a material which is used to encapsulate cells to provide a supportive extracellular matrix (ECM) environment and safeguard cells from the stresses a cell has to undergo during printing. Before bioprinting, printing speed, dispensing pressure and movement distance need to be determined for an efficient printing. All the printing parameters depend majorly on the cell line and bioink properties. Printability for a bioink can be determined by the ease with which it could be printed with good resolution and maintenance of its structure after printing. Printability of a bioink can usually be measured by the shape fidelity, resolution, biocompatibility and cell supportive ability [18]. Many researchers GB-88 have printed cell-laden structures through extrusion printing and have also developed heterogeneous tissue constructs with multiple cell lineages (summarized in Table 1 and Table 2). Although homogenous cell distribution within the construct has been achieved, cell viability gets compromised due to stress conditions that a cell experiences during printing. Direct cell printing will compromise the cell viability but printing of cells by blending with hydrogel has been shown to improve the cell viability. Table 1 Different strategies to improve the printability of bioinks. concentration to viscous hydrogels above this concentration [58]. Generally, lower concentrations of alginate are recommended for high cell viability. However, at lower concentration, achieving good resolution for printing applications is challenging. Many attempts to optimize the resolution of alginate bioinks have been reported, including optimization of alginate concentration, blending with high molecular weight polymers and tuning of printing parameters. Like the viscosity, the resolution of alginate bioinks is also dependent on concentration. Studies have reported that at 0.5 concentrations of alginate, a decrease in nozzle diameter would decrease the drop volume by almost 3-fold thus increasing the resolution. However, at a higher alginate concentration of around 1.5%.