Table 5.

The factors that were affected by low printability quality in 3D-bioprinting technique.

Bioinks	Printing Method	Factors that Affected by Low Printability Quality				Strategies to Improve Printability	References
		Viscosity of Hydrogel	Shear-Thinning Property	Scaffold Porosity	Structural Fidelity
Hydrogels	Extrusion-based bioprinting Lithography-based bioprinting	Higher viscosity of the hydrogel will result in high printing fidelity.	Shear stress increases due to high viscosity of hydrogels.	The thickness of the hydrogel layers may influence the size of the pores.	Cross-linker efficiency and structural stability for postprinting.	The optimal temperature of each hydrogel must be identified because it has influenced viscosity of the hydrogels. Increase printing resolution for shape fidelity. Hydrogels must be physically or chemically crosslinked to facilitate the shape of the 3D-structure. Several printing patterns were suggested to enhance pore structures, including zigzag and honeycomb patterns.	[60,69]
Alginate-Gelatin	Extrusion based bioprinting	High viscosity of alginate-gelatin bioinks promotes unstable and irregular forms of hydrogels during printing. The viscosity of the alginate-gelatin bioinks is influenced by the temperature of the gelatin to become gel and solid. The higher viscosity of gelatin will result in higher modulus storage. Besides, the higher viscosity of alginate will increase in loss modulus.	Not-Reported	Not-Reported	Alginate and gelatin have low structural fidelity. Loss modulus of the alginate will negatively affect the shape fidelity of the printed hydrogel.	The concentration of gelatin must be higher than alginate to ensure right viscosity and storage modulus. The optimum printing temperature for alginate-gelatin is between 20–25 °C. Alginate known as low bioadhesivity bioinks. Therefore, alginate need to be used with gelatin to provide the ligands for cell attachments and mimics the native ECM. The covalent crosslinking technique should be used to enhance the mechanical properties of alginate. The printability quality of alginate-gelatin bioinks can also be supported by the addition of an extruder heating system.	[69,70,71,72,73,74]
Agarose-Collagen	Extrusion-based bioprinting	Collagen has low viscosity and slow gelation time. Agarose has rapid gelation time and its viscosity influenced by the temperature.	Not Reported	Not Reported	Agarose supports the mechanical strength of the collagen bioinks.	Collagen type I needs to be used with agarose to enhance the viscosity, gelation time, and support the mechanical strength. The strategies to improve shear thinning and porosity structure for agarose-collagen bioinks are not reported.	[69,75]
Chitosan-Gelatin	Extrusion-based bioprinting	The viscosity increased as the concentration increases.	Flow rate increased according to the diameter of the nozzle	Chitosans have shear thinning behavior.	Chitosan-gelatin hydrogel has excellent mechanical strength.	Appropriate concentrations of the chitosan-gelatin bioinks should be used since they have influenced the viscosity of the hydrogels. The optimum size of the nozzle is necessary to monitor the printing of the hydrogel. Chitosan must be combined with other natural biomaterials for better mechanical stability.	[69,76,77]
Cellulose-Alginate	Extrusion-based bioprinting	A lower viscosity of alginate will disrupt cell viability.	Not Reported	Not Reported	Not Reported	The combination of alginate with nanofibrilated cellulose (NFC) resulting an excellent 3D printing.	[69]
Silk fibroin-Gelatin	Extrusion-based bioprinting	The viscosity of silk fibroin influenced by the temperature.	Exposure of shear force >100 s−1 towards silk fibroin bioinks during printing results in nozzle clogging.	Have interconnected pore structures that enable cellular migration activity.	Printed hydrogels that are made up of silk have high compatibility with high structural fidelity.	Mix homogeneous living cells before printing process to allow easy mixing and achieve optimal viscosity without affecting cell viability. Apply low shear force (<100 s−1) during printing to reduce shear rate. The printed hydrogel can be deposited in 80–90% of alcohol to permit a faster solidification. However, this is not suitable with cells. Silk fibroin need to combine with gelatin bioinks to produce putative cell attachments motifs.	[49,65,69,78,79]
Gelatin-Elastin	Extrusion-based printing	The viscosity of the gelatin-elastin bioinks depending on the adjusted temperature.	Shear stress increased from 0.79 to 1.17 kPa when the extrusion pressure increased from 5 kPa to 25 kPa	Not-Reported	Construct with a complex architecture shape of the scaffold will improve the printing fidelity.	Handle with a temperature of 8 °C for optimum viscosity. The final printing condition was selected as 15 kPa pressure and 30 mm s 1 at 8–10 °C, resulting in 1.08 kPa shear stress. Used cold water fish gelatin to enhance the printability of bioinks. Crosslinking with visible light is required to enhance the mechanical strength of the hydrogel. Strategies to enhance porosity structure for gelatin-elastin hydrogels are not reported.	[71,72]
Alginate-Honey	Extrusion-based bioprinting	The use of alginate alone tends to be high in viscosity and therefore difficult to print.	High viscosity of alginate induces shear thinning during the printing process.	Alginate hydrogel has low porosity structure.	Low shape fidelity.	Use honey as natural materials/remedies to reduce the viscosity of alginate, improve the structural fidelity of the printed hydrogel, and increase the gelation time. Use up to 5% concentration of honey to retain the porous structure of the printed hydrogel. Strategies to improve shear thinning for alginate-honey bioinks are not reported.	[73]
Alginate	Extrusion-based bioprinting	The viscosity of alginate bioinks influenced by the amount of alginate powder and suitable temperature use.	Not Reported	High porosity of hydrogel structure.	Not Reported	Choose the right size of nozzle/valve for printing because it affects cell viability and shear thinning rate. Alginate bioinks suitable to perform physical crosslinking to enhance shape fidelity.	[44,74]
Gelatin Methacrylate (GelMA)	Extrusion-based bioprinting	The adsoption of GelMA towards nanocellulose has impacts on the viscoelasticity of the hydrogel and it becomes easier for the hydrogel to move out from the nozzle.	Nanocellulose shows shear-thinning behavior.	Not Reported	The incorporation of GelMA with nanocellulose increased the solid content of the bioinks. Therefore, it will increase the shape fidelity of the hydrogels.	Adjusted the printing parameters based on viscoelasticity of bioinks. Used 2000 mm/min of printing speeds. Combine GelMA bioinks with nanocellulose to enhance mechanical strength of the hydrogel.	[80]
Furfuryl-Gelatin	Extrusion-based bioprinting	Insufficient viscosity for printing.	Insufficient shear thinning.	Have adequate porosity structure for cellular activity.	Low structural fidelity.	Addition of a small quantity of hyaluronic acid (HA) to enhance the viscosity of the hydrogel. Strategies for managing shear thinning are not reported. Requires crosslinking with visible light to achieve good structural fidelity.	[81]
Collagen	Extrusion-based bioprinting	Low viscosity	Increase in shear rate	The usage of collagen bioinks without a crosslinker does not produce a porous structure of hydrogel.	Weak mechanical strength.	Use of low pH, mild collagen composition showed dense collagen fibers with a large pore size. Print collagen bioinks below gelation time (35 °C) to prevent shear stress. 5% collagen is the optimum concentration to reduce shear stress and for high cell viability. Crosslink the collagen bioinks with a crosslinker (physical or chemical), or can use with other biomaterials including natural and synthetic polymers to enhance mechanical strength of the hydrogels.	[82,83]