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. 2016 Sep 27;9(10):802. doi: 10.3390/ma9100802

Table 1.

Typical three-dimensional (3D) bioprinting technologies for hard tissue and organ engineering.

Technique Working principle Main starting biomaterials Advantages Disadvantages Morphology References
Extrusion-based rapid prototyping (RP) Fluidic material is forced through a piston nozzle at a low temperature (≤−20 °C) Natural or synthetic polymer solutions A wide range of materials can be used; high accuracy; flexible; reproducible; scalable; growth factors can be incorporated; constructs with high mechanical properties can be obtained Organic solvents are needed for synthetic polymer deposition; cells are difficult to be incorporated graphic file with name materials-09-00802-i001.jpg [59]
Pneumatic extrusion-based bioplotter Polymer strands stabilized layer-by-layer in a liquid medium Natural polymer solutions, such as alginate and proteins, cells and growth factors can be incorporated Good biocompatibilities Low cell survival rate; weak mechanical properties; fragile graphic file with name materials-09-00802-i002.jpg [141]
Fused deposition modeling (FDM) Strands of heated polymers extruded through nozzles Synthetic polymers, such as acrylonitrile butadiene styrene (ABS), poly lactic acid (PLA), polyvinyl alcohol (PVA) Automated; controllable; fast; sophisticated; accurate; reproducible; scalable Limited materials can be used; cells cannot be incorporated directly graphic file with name materials-09-00802-i003.jpg [142]
FDM Strands of polymer composite extruded through a commercial FDM (MakerBot) Hydroxyapatite (HA) incorporated polycaprolactone (PCL) Automated; controllable; fast; sophisticated; accurate; reproducible; scalable Limited materials can be used; cells cannot be incorporated directly graphic file with name materials-09-00802-i004.jpg [143]
Indirect 3D bio-printing Fibrin-polymer–ceramic scaffolds manufactured by fused deposition modeling Calcium phosphate modified PCL (PCL-CaP) and treated with fibrinogen A wide range of biomaterials can be used; cells and bioactive agents can be incorporated Low accuracy of the final structures; complex processing procedures graphic file with name materials-09-00802-i005.jpg [144]
Indirect micro-stereolithography (mSTL) Tracheal cartilage regeneration on an indirect printed gelatin sponge Poly-(l-Lactide-co-ε-caprolactone)/gelatin, heparin, transforming growth factor-β1, chondrocytes A wide range of biomaterials can be used; bioactive agents can be incorporated Low accuracy of the final structures; complex processing procedures; limited mechanical properties graphic file with name materials-09-00802-i006.jpg [111]
Laser-based stereolithography (SLA) A small-spot of laser is used for solid polymers Synthetic polymers High resolution; cells can be incorporated Limited materials; low throughput graphic file with name materials-09-00802-i007.jpg [54,85]
Thermal inkjet-based AM Collagen was dissolved into phosphoric acid-based binder solution to fabricate collagen-calcium phosphate composites Collagen solutions The fabrication temperature can be reduced Low accuracy; low mechanical properties; cells cannot be incorporated graphic file with name materials-09-00802-i008.jpg [113]
Extrusion-based RP Pneumatic forced nozzles for fluidic materials Natural or synthetic polymer solutions A wide range of biomaterials can be used; cells, bioactive agents can be incorporated Nozzle easily clogging; harms to cells graphic file with name materials-09-00802-i009.jpg [35]
Inkjet-based RP Fluidic material is forced through an orifice Hyaluronic acid (HA) improved gelatin-methacrylamide (gelMA) hydrogels High mechanical properties; cells, bioactive agents can be incorporated Limited biomaterials can be used; limited height of the construct graphic file with name materials-09-00802-i010.jpg [144]
Direct write (DW) RP 3D ink writing (or robocasting) in an oil bath A concentrated colloidal gel (typically 50% HA particles suspended in an aqueous medium) Two materials can be printed in a construct Limited biomaterials can be used; limited height of the construct graphic file with name materials-09-00802-i011.jpg [95]
Double nozzle extrusion-based RP Fluidic materials are forced through two piston nozzles at a temperature about 10 °C Natural polymer hydrogels, such as gelatin, gelatin/alginate, and gelatin/alginate/fibrinogen A wide range of biomaterials can be used; cells, bioactive agents can be incorporated; branched vascular systems can be easily created; excellent biocompatibilities Weak mechanical properties; high concentration of hydrogels affects cell–cell interactions; easily being biodegraded under in vivo conditions graphic file with name materials-09-00802-i012.jpg [120,121]
Double nozzle low-temperature extrusion-based RP Fluidic materials are forced through two piston nozzles at a temperature ≤−20 °C Natural and synthetic polymer solutions A wide range of biomaterials can be used; cells, growth factors, cytokines, chemicals, genes can be incorporated; branched vascular systems can be easily created; high mechanical properties; stable; fast; controllable; sophisticated; accurate; scalable; reproducible High concentration of natural hydrogels affects cell–cell interactions; organic solvents are needed for synthetic polymer dissolution and to be removed after printing graphic file with name materials-09-00802-i013.jpg [61,62,127,128]