Application of Bioprinting in Ophthalmology

Yanfang Wang, Jiejie Wang, Ziyu Ji, Wei Yan, Hong Zhao, Wenhua Huang, Huan Liu

Article ID: 552
Vol 8, Issue 2, 2022, Article identifier:

VIEWS - 325 (Abstract) 79 (PDF)



Three-dimensional (3D) bioprinting is an emerging technology that is widely used in regenerative medicine. With the continuous development of the technology, it has attracted great attention and demonstrated promising prospects in ophthalmologic applications. In this paper, we review the three main types of 3D bioprinting technologies: Vat polymerization based bioprinting, extrusion-based bioprinting, and jetting-based bioprinting. We also present in this review the analysis of the usage of both natural and synthesized hydrogels as well as the types of cells adopted for bioinks. Cornea and retina are the two main types of ocular tissues developed in bioprinting, while other device and implants were also developed for the ocular disease treatment. We also summarize the advantages and limitations as well as the future prospects of the current bioprinting technologies based on systematic reviews.


Bioprinting, Ophthalmology, Bioinks, Biomaterials, Ocular bioprinting

Full Text:



Di Marzio N, Eglin D, Serra T, et al., 2020, Bio-Fabrication: Convergence of 3D Bioprinting and Nano-Biomaterials in Tissue Engineering and Regenerative Medicine. Front Bioeng Biotechnol, 8:326.

Moroni L, Burdick JA, Highley C, et al., 2018, Biofabrication Strategies for 3D In Vitro Models and Regenerative Medicine. Nature reviews. Materials, 3:21–37.

Hull CW, Uvp I, 1986, Apparatus for Production of Three dimensional Objects by Stereolithography. Patent US-6027324-A.

Klebe RJ, 1988, Cytoscribing: A Method for Micropositioning Cells and the Construction of Two and Three-dimensional Synthetic Tissues. Exp Cell Res, 179:362–73.

Castilho M, de Ruijter M, Beirne S, et al., 2020, Multitechnology Biofabrication: A New Approach for the Manufacturing of Functional Tissue Structures? Trends Biotechnol, 38:1316–28.

Maloca PM, Tufail A, Hasler PW, et al., 2019, 3D Printing of the Choroidal Vessels and Tumours Based on Optical Coherence Tomography. Acta Ophthalmol, 97:e313–6.

AlQattan B, Yetisen A Kand Butt H, 2018, Direct laser writing of nanophotonic structures on contact lenses. ACS Nano, 12:5130–40.

Park J, Ahn D B, Kim J, et al., 2019, Printing of Wirelessly Rechargeable Solid-state Supercapacitors for Soft, Smart Contact Lenses with Continuous Operations. Sci Adv, 5:eaay0764.

Sommer AC, Blumenthal EZ, 2019, Implementations of 3D Printing in Ophthalmology. Graefes Arch Clin Exp Ophthalmol, 257:1815–22.

Xie P, Hu Z, Zhang X, et al., 2014, Application of 3-dimensional Printing Technology to Construct an Eye Model for Fundus Viewing Study. PLoS One, 9:e109373.

Ng WL, Lee JM, Zhou M, et al., 2020, Vat Polymerization based Bioprinting-Process, Materials, Applications and Regulatory Challenges. Biofabrication, 12:022001.

Zhao W, Qin P, Zhang D, et al., 2019, Long Non-coding RNA PVT1 Encapsulated in Bone Marrow Mesenchymal Stem Cell-derived Exosomes Promotes Osteosarcoma Growth and Metastasis by Stabilizing ERG and Sponging miR-183-5p. Aging (Albany NY), 11:9581–96.

Hinczewski C, Corbel S, Chartier T, 1998, Ceramic Suspensions Suitable for Stereolithography. J Eur Ceram Soc, 18:583–90.

Zhu W, Ma X, Gou M, et al., 2016, 3D Printing of Functional Biomaterials for Tissue Engineering. Curr Opin Biotechnol, 40:103–12.

Xing JF, Zheng ML, Duan XM, 2015, Two-photon Polymerization Microfabrication of Hydrogels: An Advanced 3D Printing Technology For Tissue Engineering and Drug Delivery. Chem Soc Rev, 44:5031–9.

Nguyen AK, Narayan RJ, 2017, Two-photon Polymerization for Biological Applications. Mater Today, 20:314–22.

Jiang T, Munguia-Lopez JG, Flores-Torres S, et al., 2019, Extrusion Bioprinting of Soft Materials: An Emerging Technique for Biological Model Fabrication. Appl Phys Rev, 6:011310.

Li X, Liu B, Pei B, et al., 2020, Inkjet Bioprinting of Biomaterials. Chem Rev, 120:10793–833.

Cui X, Boland T, D’Lima DD, et al., 2012, Thermal Inkjet Printing in Tissue Engineering and Regenerative Medicine. Recent Pat Drug Deliv Formul, 6:149–155.

Nishiyama Y, Nakamura M, Henmi C, et al., 2009, Development of a Three-dimensional Bioprinter: Construction of Cell Supporting Structures Using Hydrogel and State-of the-art Inkjet Technology. J Biomech Eng, 131:035001.

Nakamura M, Iwanaga S, Henmi C, et al., 2010, Biomatrices and Biomaterials for Future Developments of Bioprinting and Biofabrication. Biofabrication, 2:0141.

Wijshoff H, 2010, The Dynamics of the Piezo Inkjet Printhead Operation. Phys Rep, 491:77–177.

Christensen K, Xu C, Chai W, et al., 2015, Freeform Inkjet Printing of Cellular Structures with Bifurcations. Biotechnol Bioeng, 112:1047–55.

Park JU, Hardy M, Kang SJ, et al., 2007, High-resolution Electrohydrodynamic Jet Printing. Nat Mater, 6:782–9.

Poellmann MJ, Barton KL, Mishra S, et al., 2011, Patterned Hydrogel Substrates for Cell Culture with Electrohydrodynamic Jet Printing. Macromol Biosci, 11:1164–8.

Dorishetty P, Dutta NK, Choudhury NR, 2020, Bioprintable Tough Hydrogels for Tissue Engineering Applications. Adv Colloid Interface Sci, 281:102163.

Gu Z, Fu J, Lin H, et al., 2019, Development of 3D Bioprinting: From Printing Methods to Biomedical Applications. Asian J Pharm Sci, 15:529–557.

Sorkio A, Koch L, Koivusalo L, et al., 2018, Human Stem Cell Based Corneal Tissue Mimicking Structures Using Laser-assisted 3D Bioprinting and Functional Bioinks. Biomaterials, 171:57–71.

Mecham RP, 2012, Overview of Extracellular Matrix. Curr Protoc Cell Biol, Chapter 10:Unit 10 11.

Pati F, Jang J, Ha DH, et al., 2014, Printing Three-dimensional Tissue Analogues with Decellularized Extracellular Matrix Bioink. Nat Commun, 5:3935.

Kim H, Park MN, Kim J, et al., 2019, Characterization of Cornea-specific Bioink: High transparency, Improved In Vivo Safety. J Tissue Eng, 10:2041731418823382.

Maqueda M, Mosquera JL, Garcia-Arumi J, et al., 2021, Repopulation of Decellularized Retinas with hiPSC-derived Retinal Pigment Epithelial and Ocular Progenitor Cells Shows Cell Engraftment, Organization and Differentiation. Biomaterials, 276:121049.

Wang F, Shi W, Li H, et al., 2020, Decellularized Porcine Cornea-derived Hydrogels for the Regeneration of Epithelium and Stroma in Focal Corneal Defects. Ocul Surf, 18:748–60.

Chameettachal S, Prasad D, Parekh Y, et al., 2021, Prevention of Corneal Myofibroblastic Differentiation In Vitro Using a Biomimetic ECM Hydrogel for Corneal Tissue Regeneration. ACS Appl Bio Mater, 4:533–44.

Bektas CK, Hasirci V, 2020, Cell Loaded 3D Bioprinted GelMA Hydrogels for Corneal Stroma Engineering. Biomater Sci, 8:438–49.

Leijten J, Seo J, Yue K, et al., 2017, Spatially and Temporally Controlled Hydrogels for Tissue Engineering. Mater Sci Eng R Rep, 119:1–35.

Lee KY, Mooney DJ, 2001, Hydrogels for Tissue Engineering. Chem Rev, 101:1869–79.

Osidak EO, Karalkin PA, Osidak MS, et al., 2019, Viscoll Collagen Solution as a Novel Bioink for Direct 3D Bioprinting. J Mater Sci Mater Med, 30:31.

Stepanovska J, Otahal M, Hanzalek K, et al., 2021, pH Modification of High-Concentrated Collagen Bioinks as a Factor Affecting Cell Viability, Mechanical Properties, and Printability. Gels, 7:252.

Wu Z, Liu J, Lin J, et al., 2022, Novel Digital Light Processing Printing Strategy Using a Collagen-Based Bioink with Prospective Cross-Linker Procyanidins. Biomacromolecules, 23:240–52.

Lee JM, Suen SK, Ng WL, et al., 2021, Bioprinting of Collagen: Considerations, Potentials, and Applications. Macromol Biosci, 21:e2000280.

Roth EA, Xu T, Das M, et al., 2004, Inkjet printing for high throughput cell patterning. Biomaterials, 25:3707–15.

Ng WL, Lee JM, Yeong WY, et al., 2017, Microvalve-based Bioprinting process, Bio-inks and Applications. Biomater Sci, 5:632–47.

Wang P, Li X, Zhu W, et al., 2018, 3D Bioprinting of Hydrogels for Retina Cell Culturing. Bioprinting (Amsterdam, Netherlands), 11:e00029.

Khalili M, Asadi M, Kahroba H, et al., 2020, Corneal Endothelium Tissue Engineering: An Evolution of Signaling Molecules, Cells, and Scaffolds toward 3D Bioprinting and Cell Sheets. J Cell Physiol, 236:3275–303.

Ashammakhi N, Ahadian S, Xu C, et al., 2019, Bioinks and Bioprinting Technologies to Make Heterogeneous and Biomimetic Tissue Constructs. Materials Today Bio, 1:100008.

West-Mays JA, Dwivedi DJ, 2006, The Keratocyte: Corneal Stromal Cell with Variable Repair Phenotypes. Int J Biochem Cell Biol, 38:1625–31.

Gouveia RM, Connon CJ, 2013, The Effects of Retinoic Acid on Human Corneal Stromal Keratocytes Cultured In Vitro Under Serum-Free Conditions. Investig Ophthalmol Visual Sci, 54:7483–91.

Isaacson A, Swioklo S, Connon CJ, 2018, 3D Bioprinting of a Corneal Stroma Equivalent. Exp Eye Res, 173:188–93.

Jin K, Wang S, Zhang Y, et al., 2019, Long Non-coding RNA PVT1 Interacts with MYC and its Downstream Molecules to Synergistically Promote Tumorigenesis. Cell Mol Life Sci, 76:4275–89.

Kim KW, Lee SJ, Park SH, et al., 2018, Ex Vivo Functionality of 3D Bioprinted Corneal Endothelium Engineered with Ribonuclease 5-Overexpressing Human Corneal Endothelial Cells. Adv Healthc Mater, 7:1800398.

Masland RH, 2011, Cell Populations of the Retina: The Proctor Lecture. Investig Ophthalmol Visual Sci, 52:4581–91.

Lorber B, Hsiao WK, Martin KR, 2016, Three-dimensional Printing of the Retina. Curr Opin Ophthalmol, 27:262–7.

Kador KE, Grogan SP, Dorthé EW, et al., 2016, Control of Retinal Ganglion Cell Positioning and Neurite Growth: Combining 3D Printing with Radial Electrospun Scaffolds. Tissue Eng Part A, 22:286–94.

Yong HE, Qing GA, Liu A, et al., 2019, 3D Bioprinting: From Structure to Function. J Zhejiang Univ, 53:407–19.

Farandos NM, Yetisen AK, Monteiro MJ, et al., 2015, Contact Lens Sensors in Ocular Diagnostics. Adv Healthc Mater, 4:792–8.

Tang H, Alqattan B, Jackson T, et al., 2020, Cost-Efficient Printing of Graphene Nanostructures on Smart Contact Lenses. ACS Applied Materials & Interfaces, 12(9): 10820-10828.

Sanchez-Tena MA, Alvarez-Peregrina C, Santos-Arias F, et al., 2019, Application of 3D Printing Technology in Scleral Cover Shell Prosthesis. J Med Syst, 43:149.

Debellemanière G, Flores M, Montard M, et al., 2016, Three dimensional Printing of Optical Lenses and Ophthalmic Surgery: Challenges and Perspectives. J Refract Surg (Thorofare NJ: 1995), 32:201–4.

John G, Michal EP, Tomasz ST, 2017, Quantitative Evaluation of Performance of Three-dimensional Printed Lenses. Opt Eng, 56:1–13.

Park SH, Su R, Jeong J, et al., 2018, 3D Printed Polymer Photodetectors. Adv Mater (Deerfield Beach, Fla.), 30:e1803980.

Callahan AB, Campbell AA, Petris C, et al., 2017, Low-Cost 3D Printing Orbital Implant Templates in Secondary Orbital Reconstructions. Ophthalmic Plastic Reconstr Surg, 33:376–80.

Dave TV, Gaur G, Chowdary N, et al., 2018, Customized 3D Printing: A Novel Approach to Migrated Orbital Implant. Saudi J Ophthalmol, 32:330–3.

Fan B, Chen H, Sun YJ, et al., 2017, Clinical Effects of 3-D Printing-assisted Personalized Reconstructive Surgery for Blowout Orbital Fractures. Graefes Arch Clin Exp Ophthalmol, 255:2051–7.

Kang S, Kwon J, Ahn CJ, et al., 2018, Generation of Customized Orbital Implant Templates Using 3-dimensional Printing for Orbital Wall Reconstruction. Eye (London, England), 32:1864–70.

Zamboulis A, Nanaki S, Michailidou G, et al., 2020, Chitosan and its Derivatives for Ocular Delivery Formulations: Recent Advances and Developments. Polymers, 12:1519.

Silva MM, Calado R, Marto J, et al., 2017, Chitosan Nanoparticles as a Mucoadhesive Drug Delivery System for Ocular Administration. Mar Drugs, 15:370.

Başaran E, Yazan Y, 2012, Ocular Application of Chitosan. Exp Opin Drug Deliv, 9:701–12.

Lynch C, Kondiah PP, Choonara YE, et al., 2019, Advances in Biodegradable Nano-Sized Polymer-Based Ocular Drug Delivery. Polymers, 11:1371.

Cho H, Jammalamadaka U, Tappa K, 2018, Nanogels for Pharmaceutical and Biomedical Applications and Their Fabrication Using 3D Printing Technologies. Materials (Basel, Switzerland), 11:302.

Flaxman SR, Bourne RR, Resnikoff S, et al., 2017, Global Causes of Blindness and Distance Vision Impairment 1990–2020: A Systematic Review and meta analysis. Lancet Global Health, 5:e1221–34.

Mathews PM, Lindsley K, Aldave AJ, et al., 2018, Etiology of Global Corneal Blindness and Current Practices of Corneal Transplantation: A Focused Review. Cornea, 37:1198–203.

Gain P, Jullienne R, He Z, et al., 2016, Global Survey of Corneal Transplantation and Eye Banking. JAMA Ophthalmol, 134:167–73.

Zhang B, Xue Q, Li J, et al., 2019, 3D bioprinting for Artificial Cornea: Challenges and Perspectives. Med Eng Phys, 71:68–78.

Fuest M, Yam GH, Mehta JS, et al., 2020, Prospects and Challenges of Translational Corneal Bioprinting. Bioengineering, 7:71.

Faye PA, Poumeaud F, Chazelas P, et al., 2021, Focus on Cell Therapy to Treat Corneal Endothelial Diseases. Exp Eye Res, 204:108462.

Campos DF, Rohde M, Ross M, et al., 2019, Corneal Bioprinting Utilizing Collagen-based Bioinks and Primary Human Keratocytes. J Biomed Mater Res Part A, 107:1945–53.

Kong B, Chen Y, Liu R, et al., 2020, Fiber Reinforced GelMA Hydrogel to Induce the Regeneration of Corneal Stroma. Nat Commun, 11:1435–5.

Kim H, Jang J, Park J, et al., 2019, Shear-induced Alignment of Collagen Fibrils Using 3D Cell Printing for Corneal Stroma Tissue Engineering. Biofabrication, 11:035017.

Holland G, Pandit A, Sanchez-Abella L, et al., 2021, Artificial Cornea: Past, Current, and Future Directions. Front Med (Lausanne), 8:770780.

Hoon M, Okawa H, Santina LD, et al., 2014, Functional Architecture of the Retina: Development and Disease. Prog Retin Eye Res, 42:44–84.

Ruiz-Alonso S, Villate-Beitia I, Gallego I, et al., 2021, Current Insights Into 3D Bioprinting: An Advanced Approach for Eye Tissue Regeneration. Pharmaceutics, 13:308.

Lorber B, Hsiao WK, Hutchings IM, et al., 2014, Adult Rat Retinal Ganglion Cells and Glia can be Printed by Piezoelectric Inkjet Printing. Biofabrication, 6:015001.

Masaeli E, Forster V, Picaud S, et al., 2020, Tissue Engineering of Retina Through High Resolution 3-Dimensional Inkjet Bioprinting. Biofabrication, 12:025006.

Masaeli E, Marquette C, 2020, Direct-Write Bioprinting Approach to Construct Multilayer Cellular Tissues. Front Bioeng Biotechnol, 7:478.

Meek KM, Knupp C, 2015, Corneal Structure and Transparency. Prog Retin Eye Res, 49:1–16.

Kutlehria S, Dinh TC, Bagde A, et al., 2020, High-throughput 3D Bioprinting of Corneal Stromal Equivalents. J Biomed Mater Res B Appl Biomater, 108:2981–94.

Mahdavi SS, Abdekhodaie MJ, Kumar H, et al., 2020, Stereolithography 3D Bioprinting Method for Fabrication of Human Corneal Stroma Equivalent. Ann Biomed Eng, 48:1955–70.

Shi P, Edgar TY, Yeong WY, et al., 2017, Hybrid Three dimensional (3D) Bioprinting of Retina Equivalent for Ocular Research. Int J Bioprint, 3:8.

Worthington KS, Wiley LA, Kaalberg EE, et al., 2017, Two-photon Polymerization for Production of Human iPSC derived Retinal Cell Grafts. Acta Biomater, 55:385–95.



  • There are currently no refbacks.

Copyright (c) 2022 Author(s).

License URL: