The New Era of Tissue Engineering - 3D Printing of Organs and Tissue Constructs




3D Bioprinting, Tissue engineering, Biomaterials


Tissue engineering and regenerative medicine research has utilized three-dimensional (3D) bioprinting as a promising technique for fabricating complex functional biological constructs mimicking native tissue for repair and/or replacement of damaged organs or tissues. It has shown to alleviate the hurdles of conventional tissue engineering methods based on scaffolding and microengineering by precise biomimetic properties and controlled layer-by-layer assembly of biomaterials in a desired 3D pattern. 3D bioprinting involves the top-down approach of building complex tissue with precise geometries using computer graphic generated anatomically accurate 3D models of the tissue. In this comprehensive review, we highlight 3D bioprinting technologies such as ink-jet printing, extrusion printing, stereolithography and laser assisted techniques and applications of 3D bioprinting for construction of tissues such as skin, cardiac, bone and cartilage. We will discuss current challenges with 3D bioprinting technologies and future prospects for advancements for efficient and effective construction of native tissues.


Mandrycky C, Phong K, Zheng Y. Tissue engineering toward organ-specific regeneration and disease modeling. MRS Commun. 2017;7(3):332-347. doi:10.1557/mrc.2017.58

Chen M, Jiang R, Deng N, et al. Natural polymer-based scaffolds for soft tissue repair. Front Bioeng Biotechnol. 2022;10:954699. Published 2022 Jul 19. doi:10.3389/fbioe.2022.954699

Thompson CL, Fu S, Heywood HK, et al. Mechanical Stimulation: A Crucial Element of Organ-on-Chip Models. Front. Bioeng. Biotechnol. 2020;8:602646. doi: 10.3389/fbioe.2020.602646

Heinonen I, Kalliokoski KK, Hannukainen JC, et al. Organ-specific physiological responses to acute physical exercise and long-term training in humans. Physiology (Bethesda). 2014;29(6):421-436. doi:10.1152/physiol.00067.2013

Agarwal S, Saha S, Balla VK, et al. Current Developments in 3D Bioprinting for Tissue and Organ Regeneration–A Review. Front. Mech. Eng.2020; 6:589171. doi:10.3389/fmech.2020.589171

Rafelski, S., Marshall, W. Building the cell: design principles of cellular architecture. Nat Rev Mol Cell Biol. 2008;9, 593–602.

Dey M, Ozbolat IT. 3D bioprinting of cells, tissues and organs. Sci Rep. 2020;10(1):14023. doi:10.1038/s41598-020-70086-y

Zhang YS, Yue K, Aleman J, et al. 3D Bioprinting for Tissue and Organ Fabrication. Ann Biomed Eng. 2017;45(1):148-163. doi:10.1007/s10439-016-1612-8

Gaharwar, A.K., Singh, I. & Khademhosseini, A. Engineered biomaterials for in situ tissue regeneration. Nat Rev Mater. 2020; 5, 686–705. doi:10.1038/s41578-020-0209-x

Vanaei S, Parizi M S, Salemizadehparizi F, et al. An overview on materials and techniques in 3D bioprinting toward biomedical application. Engineered Regeneration, 2021, 2: 1-18. doi:10.1016/j.engreg.2020.12.001

Yu Y, Moncal KK, Li J, et al. Three-dimensional bioprinting using self-assembling scalable scaffold-free "tissue strands" as a new bioink. Sci Rep. 2016;6:28714. doi:10.1038/srep28714

Zhang W, Liu Y, Zhang H. Extracellular matrix: an important regulator of cell functions and skeletal muscle development. Cell Biosci. 2021;11(1):65. doi:10.1186/s13578-021-00579-4

Cui X, Boland T, D'Lima DD, et al. Thermal inkjet printing in tissue engineering and regenerative medicine. Recent Pat Drug Deliv Formul. 2012;6(2):149-155. doi:10.2174/187221112800672949

Bernasconi R, Brovelli S, Viviani P, et al. Piezoelectric drop-on-demand inkjet printing of high-viscosity inks. Advanced Engineering Materials, 2022, 24(1): 2100733. doi:10.1002/adem.202100733

J. Plog, Y. Jiang, Y. Pan, et al. Electrostatic charging and deflection of droplets for drop-on-demand 3D printing within confinements. Additive Manufacturing. 2020; 36:101400, doi:10.1016/j.addma.2020.101400

Habib MA, Khoda B. Rheological Analysis of Bio-ink for 3D Bio-printing Processes. J Manuf Process. 2022;76:708-718. doi:10.1016/j.jmapro.2022.02.048

Wu J, Wu C, Zou S, et al. Investigation of Biomaterial Ink Viscosity Properties and Optimization of the Printing Process Based on Pattern Path Planning. Bioengineering. 2023; 10(12):1358. doi:10.3390/bioengineering10121358

Habib MA, Khoda B. Rheological Analysis of Bio-ink for 3D Bio-printing Processes. J Manuf Process. 2022;76:708-718. doi:10.1016/j.jmapro.2022.02.048

Xu C, Chai W, Huang Y, et al. Scaffold-free inkjet printing of three-dimensional zigzag cellular tubes. Biotechnol Bioeng. 2012;109(12):3152-3160. doi:10.1002/bit.24591

Khanna A, Zamani M, Huang NF. Extracellular Matrix-Based Biomaterials for Cardiovascular Tissue Engineering. J Cardiovasc Dev Dis. 2021;8(11):137. doi:10.3390/jcdd8110137

Varchanis S, Haward SJ, Hopkins CC, et al. Transition between solid and liquid state of yield-stress fluids under purely extensional deformations. Proc Natl Acad Sci U S A. 2020;117(23):12611-12617. doi:10.1073/pnas.1922242117

Yin X, Ren J, Lan W, et al. Microfluidics-assisted optimization of highly adhesive haemostatic hydrogel coating for arterial puncture. Bioact Mater. 2021;12:133-142. doi:10.1016/j.bioactmat.2021.10.009

Malinauskas, M., Žukauskas, A., Hasegawa, S., et al. Ultrafast laser processing of materials: from science to industry. Light Sci Appl. 2016; 5, e16133. doi:10.1038/lsa.2016.133

Ringeisen, B.R., et al. (2010). Biological Laser Printing (BioLP) for High Resolution Cell Deposition. In: Ringeisen, B., Spargo, B., Wu, P. (eds) Cell and Organ Printing. Springer, Dordrecht. doi:10.1007/978-90-481-9145-1_5

Zhuang X, Deng G, Wu X, et al. Recent advances of three-dimensional bioprinting technology in hepato-pancreato-biliary cancer models. Front Oncol. 2023;13:1143600. doi:10.3389/fonc.2023.1143600

Wang J, Cui Z, Maniruzzaman M. Bioprinting: A focus on improving bioink printability and cell performance based on different process parameters. Int J Pharm. 2023;640:123020. doi:10.1016/j.ijpharm.2023.123020

Keriquel V, Oliveira H, Rémy M, et al. In situ printing of mesenchymal stromal cells, by laser-assisted bioprinting, for in vivo bone regeneration applications. Sci Rep. 2017;7(1):1778. doi:10.1038/s41598-017-01914-x

Sharifi S, Sharifi H, Akbari A, et al. Systematic optimization of visible light-induced crosslinking conditions of gelatin methacryloyl (GelMA). Sci Rep. 2021;11(1):23276. doi:10.1038/s41598-021-02830-x

Thomas S, Senellart P. The race for the ideal single-photon source is on. Nat Nanotechnol. 2021;16(4):367-368. doi:10.1038/s41565-021-00851-1

Jang, JW., Min, KE., Kim, C., et al. Review: Scaffold Characteristics, Fabrication Methods, and Biomaterials for the Bone Tissue Engineering. Int. J. Precis. Eng. Manuf. 24, 511–529 (2023).doi:10.1007/s12541-022-00755-7

Inui A, Sekine H, Sano K, et al. Generation of a large-scale vascular bed for the in vitro creation of three-dimensional cardiac tissue. Regen Ther. 2019;11:316-323. doi:10.1016/j.reth.2019.10.001

Hasan A, Soliman S, El Hajj F, et al. Fabrication and In Vitro Characterization of a Tissue Engineered PCL-PLLA Heart Valve. Sci Rep. 2018;8(1):8187. doi:10.1038/s41598-018-26452-y

Ebling, F. John G. and Montagna, William. "human skin". Encyclopedia Britannica, 9 Apr. 2024,

Olejnik A, Semba JA, Kulpa A, et al. 3D Bioprinting in Skin Related Research: Recent Achievements and Application Perspectives. ACS Synth Biol. 2022;11(1):26-38. doi:10.1021/acssynbio.1c00547

Herrmann, K.A., Kohan, A.A., Gaeta, M.C., et al. PET/MRI: Applications in Clinical Imaging. Curr Radiol Rep.2013; 1, 161–176. doi:10.1007/s40134-013-0021-0

Zhang Y, Yan J, Liu Y, et al. Human Amniotic Fluid Stem Cell-Derived Exosomes as a Novel Cell-Free Therapy for Cutaneous Regeneration. Front Cell Dev Biol. 2021;9:685873. doi:10.3389/fcell.2021.685873

Guido, M., Sarcognato, S., Sacchi, D., et al. (2019). The Anatomy and Histology of the Liver and Biliary Tract. In: D'Antiga, L. (eds) Pediatric Hepatology and Liver Transplantation. Springer, Cham. doi:10.1007/978-3-319-96400-3_3

Zhang, Y.S., Haghiashtiani, G., Hübscher, T., et al. 3D extrusion bioprinting. Nat Rev Methods Primers. 2021; 1, 75. doi:10.1038/s43586-021-00073-8

Ma, L., Wang, Y., Wang, J., et al. Design and fabrication of a liver-on-a-chip platform for convenient, highly efficient, and safe in situ perfusion culture of 3D hepatic spheroids. Lab on a chip. 2018;18 17, 2547-2562 .

Kim Y, Zharkinbekov Z, Sarsenova M, et al. Recent Advances in Gene Therapy for Cardiac Tissue Regeneration. Int J Mol Sci. 2021;22(17):9206. doi:10.3390/ijms22179206

Tsao CW, Aday AW, Almarzooq ZI, et al. Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association [published correction appears in Circulation. 2022 Sep 6;146(10):e141]. Circulation. 2022;145(8):e153-e639. doi:10.1161/CIR.0000000000001052

Wang Z, Wang L, Li T, et al. 3D bioprinting in cardiac tissue engineering. Theranostics. 2021;11(16):7948-7969. doi:10.7150/thno.61621

Tarassoli SP, Jessop ZM, Jovic T, et al. Candidate Bioinks for Extrusion 3D Bioprinting-A Systematic Review of the Literature. Front Bioeng Biotechnol. 2021;9:616753. doi:10.3389/fbioe.2021.616753

Gao Q, Liu Z, Lin Z, et al. 3D bioprinting of vessel-like structures with multilevel fluidic channels. ACS biomaterials science & engineering, 2017, 3(3): 399-408. doi:10.1021/acsbiomaterials.6b00643

Murphy, S.V., De Coppi, P. & Atala, A. Opportunities and challenges of translational 3D bioprinting. Nat Biomed Eng. 2020; 4, 370–380. doi:10.1038/s41551-019-0471-7

Yamanaka K, Yamamoto K, Sakai Y, et al. Seeding of mesenchymal stem cells into inner part of interconnected porous biodegradable scaffold by a new method with a filter paper. Dent Mater J. 2015;34(1):78-85. doi:10.4012/dmj.2013-330

Shi-hui Chen, Li-zhen Zheng, Xin-hui Xie, et al. Comparative study of poly (lactic-co-glycolic acid)/tricalcium phosphate scaffolds incorporated or coated with osteogenic growth factors for enhancement of bone regeneration. Journal of Orthopaedic Translation. 2014;2(2):91-104. doi:10.1016/

Zhou X, Feng W, Qiu K, et al. BMP-2 Derived Peptide and Dexamethasone Incorporated Mesoporous Silica Nanoparticles for Enhanced Osteogenic Differentiation of Bone Mesenchymal Stem Cells. ACS Appl Mater Interfaces. 2015;7(29):15777-15789. doi:10.1021/acsami.5b02636

Wen, Y., Xun, S., Haoye, M., et al. 3D printed porous ceramic scaffolds for bone tissue engineering: a review. Biomaterials science. 2017; 5(9), 1690-1698. doi:10.1039/C7BM00315C

Kang, HW., Lee, S., Ko, I., et al. A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat Biotechnol. 2016; 34, 312-319. doi:10.1038/nbt.3413

Albanna M, Binder KW, Murphy SV, et al. In Situ Bioprinting of Autologous Skin Cells Accelerates Wound Healing of Extensive Excisional Full-Thickness Wounds. Sci Rep. 2019;9(1):1856. doi:10.1038/s41598-018-38366-w

Lee S, Sani ES, Spencer AR, et al. Human-Recombinant-Elastin-Based Bioinks for 3D Bioprinting of Vascularized Soft Tissues. Adv Mater. 2020;32(45):e2003915. doi:10.1002/adma.202003915

Jin, Q., Fu, Y., Zhang, G., et al. Nanofiber electrospinning combined with rotary bioprinting for fabricating small-diameter vessels with endothelium and smooth muscle. Composites Part B: Engineering. 2022; 234, 109691. doi:10.1016/j.compositesb.2022.109691

Vyas, C., Mishbak, H., Cooper, G., et al. Biological perspectives and current biofabrication strategies in osteochondral tissue engineering. Biomanuf Rev. 2020;5, 2. doi:10.1007/s40898-020-00008-y

Zhang J, Wehrle E, Rubert M, et al. 3D Bioprinting of Human Tissues: Biofabrication, Bioinks, and Bioreactors. Int J Mol Sci. 2021;22(8):3971. doi:10.3390/ijms22083971

Cabral LRB, Teixeira LN, Gimenez RP, et al. Effect of Hyaluronic Acid and Poly-L-Lactic Acid Dermal Fillers on Collagen Synthesis: An in vitro and in vivo Study. Clin Cosmet Investig Dermatol. 2020;13:701-710. doi:10.2147/CCID.S266015

Khanna, A. Fabrication of Human Serum Albumin Film for Enhanced Hemocompatibility and Mitigation of Intimal Hyperplasia Under Physiologically Relevant Flow Shear Conditions. All Dissertations. 2017; 2060.

Lu X, Khanna A, Luzinov I, et al. Surface modification of polypropylene surgical meshes for improving adhesion with poloxamine hydrogel adhesive. J Biomed Mater Res B Appl Biomater. 2019;107(4):1047-1055. doi:10.1002/jbm.b.34197

Khanna A, Oropeza BP, Huang NF. Engineering Spatiotemporal Control in Vascularized Tissues. Bioengineering (Basel). 2022;9(10):555. doi:10.3390/bioengineering9100555

Khanna A, Ayan B, Undieh AA, et al. Advances in three-dimensional bioprinted stem cell-based tissue engineering for cardiovascular regeneration. J Mol Cell Cardiol. 2022;169:13-27. doi:10.1016/j.yjmcc.2022.04.017

Pias SC. Pathways of Oxygen Diffusion in Cells and Tissues : Hydrophobic Channeling via Networked Lipids. Adv Exp Med Biol. 2020;1232:183-190. doi:10.1007/978-3-030-34461-0_23

Huang NF, Serpooshan V, Morris VB, et al. Big bottlenecks in cardiovascular tissue engineering. Commun Biol. 2018;1:199. doi:10.1038/s42003-018-0202-8

Khanna A., (2015). Fabrication of Human Serum Albumin film for enhanced Hemocompatibility and Vascular Compatibility. Transactions of the Annual Meeting of Society for Biomaterials.

Khanna A., (2017). Fabrication of human Serum Albumin film on expanded polytetrafluoroethylene for enhanced hemocompatibility and adhesion strength. Transactions of the Annual Meeting of Society for Biomaterials.

Khanna, A., et al. (2023). Extracellular Matrix Bioactive Molecules and Cell Behavior Modeling. Handbook of the Extracellular Matrix: Biologically-Derived Materials. F. R. A. Maia, J. M. Oliveira and R. L. Reis. Cham, Springer International Publishing: 1-18.

Khanna A, Oropeza BP, Huang NF. Growth Factors Regulation in Angiogenesis. Encyclopedia. Available at: Accessed April 9, 2024.

Khanna A, Oropeza BP, Huang NF. Cardiovascular human organ-on-a-chip platform for disease modeling, drug development, and personalized therapy. J Biomed Mater Res A. 2024;112(4):512-523. doi:10.1002/jbm.a.37602




How to Cite

Khanna, A. (2024). The New Era of Tissue Engineering - 3D Printing of Organs and Tissue Constructs. BME Horizon, 2(1).