{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:33:40Z","timestamp":1793424820518,"version":"4.5.0"},"reference-count":113,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY032181"],"award-info":[{"award-number":["EY032181"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aiche.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Bioengineering &amp; Transla Med"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The human eye, a masterpiece of evolution, orchestrates the intricate process of vision. The retina is a tissue with a layered structure that plays a critical role in converting light signals into neural impulses interpretable by the brain. Various eye conditions such as glaucoma, retinitis pigmentosa, age\u2010related macular degeneration, and other retinopathies are characterized by damage or degeneration in the retina. Recent strides in organoid cultivation and advanced three\u2010dimensional (3D) bioengineering technologies offer promising avenues for potential therapeutic interventions. Compared to traditional two\u2010dimensional cell culture models, which are non\u2010natural and limited in accuracy, 3D models, including organoids, electrospinning constructs, microfabrication\u2010based scaffolds, and hydrogel systems, are more delicate, especially in recapitulating tissue architecture, offering spatial patterning, and enabling vascularization. Retinal organoids are 3D multicellular structures derived from stem cells that can mimic the retina's layered architecture and functionality. However, their inherent complexity, including the presence of multiple differentiated cell types, may not be necessary for all disease modeling applications. In contrast, engineered 3D technologies can be tailored to specific retinal diseases by incorporating only the most relevant cell types, matrix stiffness, and spatial arrangements, offering greater experimental control and reproducibility in targeted therapeutic testing. In the following paper, we will discuss organoid generation in detail. Besides retinal organoids, bioprinting is another promising avenue for regenerative medicines. We further review a suite of 3D fabrication strategies, including inkjet and laser\u2010assisted bioprinting, electrospun scaffolds, and hydrogel systems, and evaluate their current and potential applications in modeling retinal diseases and developing translational therapies. We will also delve into the contemporary advancements in retinal therapies, particularly emphasizing the roles and prospects of organoid and engineered 3D technologies.<\/jats:p>","DOI":"10.1002\/btm2.70051","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T09:10:42Z","timestamp":1755162642000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>Three\u2010dimensional<\/scp>\n                    tissue engineering and organoid technologies for retinal regeneration and therapy"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5582-7000","authenticated-orcid":false,"given":"Yiqi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Biology Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinglong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Arts and Sciences Tufts University  Medford Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn0901-877"},{"key":"e_1_2_14_3_1","volume-title":"Anatomy, Head and Neck: Eye Retina","author":"Nguyen KH","year":"2023"},{"key":"e_1_2_14_4_1","volume-title":"Anatomy, Head and Neck, Eye","author":"Rehman I","year":"2023"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1042\/BIO20200058"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2008.10.001"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.2147\/CIA.S143508"},{"key":"e_1_2_14_8_1","article-title":"Anti\u2010vascular endothelial growth factor for neovascular age\u2010related macular degeneration","volume":"3","author":"Solomon SD","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.1009599"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2015.89"},{"issue":"11","key":"e_1_2_14_11_1","first-page":"887","article-title":"Glaucoma is second leading cause of blindness globally","volume":"82","author":"Kingman S","year":"2004","journal-title":"Bull World Health Organ"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.3192"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2011.11.003"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx184"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1609-2"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2021.09.001"},{"key":"e_1_2_14_17_1","doi-asserted-by":"crossref","unstructured":"WangQ WangY JiangYDD et al.OPTN protects retinal ganglion cells and ameliorates neuroinflammation in optic neuropathies. bioRxiv.2025. doi:10.1101\/2025.01.09.632264","DOI":"10.1101\/2025.01.09.632264"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.4103\/tjo.tjo_63_20"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2022.09.009"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.12.7.23"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2015.02.011"},{"key":"e_1_2_14_22_1","first-page":"2","article-title":"Indirect traumatic optic neuropathy","volume":"3","author":"Singman EL","year":"2016","journal-title":"Mil Med Res"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2011.1756"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2016.03.002"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/OPX.0000000000001407"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70111-5"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10123343"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05134-3"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.13034"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.11.004"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-191150"},{"key":"e_1_2_14_32_1","article-title":"Steroids for traumatic optic neuropathy","volume":"2013","author":"Yu\u2010Wai\u2010Man P","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/encyclopedia3010007"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.06.018"},{"key":"e_1_2_14_35_1","first-page":"513","article-title":"The diagnosis and treatment of age\u2010related macular degeneration","volume":"117","author":"Stahl A","year":"2020","journal-title":"Dtsch Arztebl Int"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69740-7"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellin.2024.100223"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.350192"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.08.014"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61376-3"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2015.04.005"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10997"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.513713"},{"key":"e_1_2_14_44_1","first-page":"10","article-title":"Retinal ganglion cell transplantation: approaches for overcoming challenges to functional integration","volume":"10","author":"Zhang KY","year":"2021","journal-title":"Cells"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2022.03.001"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6257(03)00030-4"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2013.07.009"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00021.2004"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2014.06.002"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.032662199"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.149"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1384"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1212677110"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.00824"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05161"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60028-2"},{"key":"e_1_2_14_57_1","first-page":"920","article-title":"Long\u2010term survival and differentiation of retinal neurons derived from human embryonic stem cell lines in un\u2010immunosuppressed mouse retina","volume":"18","author":"Hambright D","year":"2012","journal-title":"Mol Vis"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-02955-3"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2019.100779"},{"key":"e_1_2_14_60_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.585675"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.62.13.26"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2019.0090"},{"key":"e_1_2_14_63_1","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2015-0125"},{"key":"e_1_2_14_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2022.10.011"},{"key":"e_1_2_14_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2022.10.010"},{"key":"e_1_2_14_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202007949"},{"key":"e_1_2_14_67_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.25.649.912"},{"key":"e_1_2_14_68_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00120.2020"},{"key":"e_1_2_14_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07935"},{"key":"e_1_2_14_70_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910244"},{"key":"e_1_2_14_71_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-0812"},{"key":"e_1_2_14_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2011.12.055"},{"key":"e_1_2_14_73_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.674"},{"key":"e_1_2_14_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2011.429"},{"key":"e_1_2_14_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09941"},{"key":"e_1_2_14_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.05.009"},{"key":"e_1_2_14_77_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1324212111"},{"key":"e_1_2_14_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5047"},{"key":"e_1_2_14_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7286"},{"key":"e_1_2_14_80_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy187"},{"key":"e_1_2_14_81_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19040936"},{"key":"e_1_2_14_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2022.12.005"},{"key":"e_1_2_14_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2016.08.010"},{"key":"e_1_2_14_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2015.05.015"},{"key":"e_1_2_14_85_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.3239"},{"key":"e_1_2_14_86_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.3089"},{"key":"e_1_2_14_87_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2317285121"},{"key":"e_1_2_14_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.02.005"},{"key":"e_1_2_14_89_1","doi-asserted-by":"publisher","DOI":"10.1177\/2041731414554139"},{"key":"e_1_2_14_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2017.03.039"},{"key":"e_1_2_14_91_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13030308"},{"key":"e_1_2_14_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsamd.2016.04.001"},{"key":"e_1_2_14_93_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-8694"},{"key":"e_1_2_14_94_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-7199"},{"key":"e_1_2_14_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2013.04.048"},{"key":"e_1_2_14_96_1","article-title":"Hybrid three\u2010dimensional (3D) bioprinting of retina equivalent for ocular research","volume":"3","author":"Shi P","year":"2017","journal-title":"Int J Bioprint"},{"key":"e_1_2_14_97_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.2661"},{"key":"e_1_2_14_98_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.bprint.2018.e00029","article-title":"3D bioprinting of hydrogels for retina cell culturing","volume":"11","author":"Wang P","year":"2018","journal-title":"Bioprinting"},{"key":"e_1_2_14_99_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2015.0373"},{"key":"e_1_2_14_100_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1255782"},{"key":"e_1_2_14_101_1","doi-asserted-by":"publisher","DOI":"10.2174\/187221112800672949"},{"key":"e_1_2_14_102_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-09957-5"},{"key":"e_1_2_14_103_1","doi-asserted-by":"publisher","DOI":"10.3390\/app11052154"},{"key":"e_1_2_14_104_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00909.2011"},{"key":"e_1_2_14_105_1","unstructured":"HouriS KerschenG.MEMS\u2010EYE: A M\/NEMS platform for the investigation of multi\u2010physical and complex nonlinear systems.2023."},{"key":"e_1_2_14_106_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-024-04007-5"},{"key":"e_1_2_14_107_1","doi-asserted-by":"publisher","DOI":"10.3390\/gels10110717"},{"key":"e_1_2_14_108_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsabm.4c01376"},{"key":"e_1_2_14_109_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-73730-9"},{"key":"e_1_2_14_110_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2017.11.001"},{"key":"e_1_2_14_111_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-111020-090812"},{"key":"e_1_2_14_112_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01024-9"},{"key":"e_1_2_14_113_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-023-10661-8"},{"key":"e_1_2_14_114_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomimetics9120733"}],"container-title":["Bioengineering &amp; Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/btm2.70051","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T18:13:35Z","timestamp":1763144015000},"score":1,"resource":{"primary":{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/10.1002\/btm2.70051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,14]]},"references-count":113,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/btm2.70051"],"URL":"https:\/\/doi.org\/10.1002\/btm2.70051","archive":["Portico"],"relation":{},"ISSN":["2380-6761","2380-6761"],"issn-type":[{"value":"2380-6761","type":"print"},{"value":"2380-6761","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,14]]},"assertion":[{"value":"2025-01-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70051"}}