{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:36:33Z","timestamp":1788456993483,"version":"build-2803163510"},"reference-count":115,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Retinal degenerative diseases such as age-related macular degeneration (AMD) represent a leading cause of blindness, resulting in permanent damage to retinal cells that are essential for maintaining normal vision. Around 12% of people over the age of 65 have some form of retinal degenerative disease. Whilst antibody-based drugs have revolutionised treatment of neovascular AMD, they are only effective at an early stage and cannot prevent eventual progression or allow recovery of previously lost vision. Hence, there is a clear unmet need to find innovative treatment strategies to develop a long-term cure. The replacement of damaged retinal cells is thought to be the best therapeutic strategy for the treatment of patients with retinal degeneration. Advanced therapy medicinal products (ATMPs) are a group of innovative and complex biological products including cell therapy medicinal products, gene therapy medicinal products, and tissue engineered products. Development of ATMPs for the treatment of retinal degeneration diseases has become a fast-growing field of research because it offers the potential to replace damaged retinal cells for long-term treatment of AMD. While gene therapy has shown encouraging results, its effectiveness for treatment of retinal disease may be hampered by the body\u2019s response and problems associated with inflammation in the eye. In this mini-review, we focus on describing ATMP approaches including cell- and gene-based therapies for treatment of AMD along with their applications. We also aim to provide a brief overview of biological substitutes, also known as scaffolds, that can be used for delivery of cells to the target tissue and describe biomechanical properties required for optimal delivery. We describe different fabrication methods for preparing cell-scaffolds and explain how the use of artificial intelligence (AI) can aid with the process. We predict that combining AI with 3D bioprinting for 3D cell-scaffold fabrication could potentially revolutionise retinal tissue engineering and open up new opportunities for developing innovative platforms to deliver therapeutic agents to the target tissues.<\/jats:p>","DOI":"10.3390\/ph16040620","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T02:01:11Z","timestamp":1681956071000},"page":"620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Advanced Therapy Medicinal Products for Age-Related Macular Degeneration; Scaffold Fabrication and Delivery Methods"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6612-1628","authenticated-orcid":false,"given":"Hanieh","family":"Khalili","sequence":"first","affiliation":[{"name":"School of Biomedical Science, University of West London, London W5 5RF, UK"},{"name":"School of Pharmacy, University College London, London WC1N 1AX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid Heidari","family":"Kashkoli","sequence":"additional","affiliation":[{"name":"School of Biomedical Science, University of West London, London W5 5RF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4831-112X","authenticated-orcid":false,"given":"David Edward","family":"Weyland","sequence":"additional","affiliation":[{"name":"School of Biomedical Science, University of West London, London W5 5RF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sama","family":"Pirkalkhoran","sequence":"additional","affiliation":[{"name":"School of Biomedical Science, University of West London, London W5 5RF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiktoria Roksana","family":"Grabowska","sequence":"additional","affiliation":[{"name":"School of Biomedical Science, University of West London, London W5 5RF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,20]]},"reference":[{"key":"ref_1","first-page":"e29583","article-title":"Age-related macular degeneration: Epidemiology, pathophysiology, diagnosis, and treatment","volume":"14","author":"Vyawahare","year":"2022","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41392-022-01251-0","article-title":"Aging and aging-related diseases: From molecular mechanisms to interventions and treatments","volume":"7","author":"Guo","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_3","first-page":"513","article-title":"The diagnosis and treatment of age-related macular degeneration","volume":"117","author":"Stahl","year":"2020","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1038\/s41433-022-02097-0","article-title":"Developing and validating a multivariable prediction model which predicts progression of intermediate to late age-related macular degeneration-the PINNACLE trial protocol","volume":"37","author":"Sutton","year":"2023","journal-title":"Eye"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.mam.2012.04.005","article-title":"Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor\/retinal pigment epithelium\/Bruch\u2019s membrane\/choriocapillaris complex","volume":"33","author":"Bhutto","year":"2012","journal-title":"Mol. Asp. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Galindo-Camacho, R.M., Blanco-Llamero, C., da Ana, R., Fuertes, M.A., Se\u00f1or\u00e1ns, F.J., Silva, A.M., Garc\u00eda, M.L., and Souto, E.B. (2022). Therapeutic approaches for age-related macular degeneration. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911769"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Prakoso, A.T., Basri, H., Adanta, D., Yani, I., Ammarullah, M.I., Akbar, I., Ghazali, F.A., Syahrom, A., and Kamarul, T. (2023). The effect of tortuosity on permeability of porous scaffold. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020427"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.preteyeres.2017.03.002","article-title":"The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD","volume":"60","author":"Datta","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/ajcn\/73.2.209","article-title":"Prospective study of dietary fat and the risk of age-related macular degeneration","volume":"73","author":"Cho","year":"2001","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.preteyeres.2008.11.004","article-title":"Age-related maculopathy\u2014Linking aetiology and pathophysiological changes to the ischaemia hypothesis","volume":"28","author":"Feigl","year":"2009","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/s13287-022-02894-0","article-title":"Human-induced pluripotent stem cells-derived retinal pigmented epithelium, a new horizon for cells-based therapies for age-related macular degeneration","volume":"13","author":"Dehghan","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/path.4266","article-title":"Mechanisms of age-related macular degeneration and therapeutic opportunities: Pathology, genetics, animal models, and therapeutic rationale of AMD","volume":"232","author":"LeCouter","year":"2014","journal-title":"J. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ruan, Y., Jiang, S., and Gericke, A. (2021). Age-related macular degeneration: Role of oxidative stress and blood vessels. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031296"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Fabre, M., Mateo, L., Lamaa, D., Baillif, S., Pag\u00e8s, G., Demange, L., Ronco, C., and Benhida, R. (2022). Recent advances in age-related macular degeneration therapies. Molecules, 27.","DOI":"10.3390\/molecules27165089"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tarau, I.-S., Berlin, A., Curcio, C.A., and Ach, T. (2019). The cytoskeleton of the retinal pigment epithelium: From normal aging to age-related macular degeneration. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143578"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e146604","DOI":"10.1172\/jci.insight.146604","article-title":"An inducible Cre mouse for studying roles of the RPE in retinal physiology and disease","volume":"6","author":"Choi","year":"2021","journal-title":"JCI Insight"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/eye.2016.216","article-title":"Structural and molecular changes in the aging choroid: Implications for age-related macular degeneration","volume":"31","author":"Chirco","year":"2017","journal-title":"Eye"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.stem.2018.05.013","article-title":"Regenerating eye tissues to preserve and restore vision","volume":"22","author":"Stern","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.7150\/ijbs.49890","article-title":"The role of inflammation in age-related macular degeneration","volume":"16","author":"Tan","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4487","DOI":"10.1007\/s00018-021-03796-9","article-title":"The complement system in age-related macular degeneration","volume":"78","author":"Armento","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1111\/ceo.13834","article-title":"Retinal pigment epithelium and age-related macular degeneration: A review of major disease mechanisms","volume":"48","author":"Somasundaran","year":"2020","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.3389\/fphar.2018.01280","article-title":"Oxidative stress in age-related macular degeneration: Nrf2 as therapeutic target","volume":"9","author":"Bellezza","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Dom\u00e8nech, E.B., and Marfany, G. (2020). The relevance of oxidative stress in the pathogenesis and therapy of retinal dystrophies. Antioxidants, 9.","DOI":"10.3390\/antiox9040347"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Rohowetz, L.J., Kraus, J.G., and Koulen, P. (2018). Reactive oxygen species-mediated damage of retinal neurons: Drug development targets for therapies of chronic neurodegeneration of the retina. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113362"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ruan, Y., Jiang, S., Musayeva, A., and Gericke, A. (2020). Oxidative stress and vascular dysfunction in the retina: Therapeutic strategies. Antioxidants, 9.","DOI":"10.3390\/antiox9080761"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Cho, Y.-K., Park, D.-H., and Jeon, I.-C. (2021). Medication trends for age-related macular degeneration. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111837"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3164","DOI":"10.1167\/iovs.04-1369","article-title":"Flavonoids protect human retinal pigment epithelial cells from oxidative-stress\u2013induced death","volume":"47","author":"Hanneken","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Csader, S., Korhonen, S., Kaarniranta, K., and Schwab, U. (2022). The effect of dietary supplementations on delaying the progression of age-related macular degeneration: A systematic review and meta-analysis. Nutrients, 14.","DOI":"10.3390\/nu14204273"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Eisenhauer, B., Natoli, S., Liew, G., and Flood, V.M. (2017). Lutein and zeaxanthin-food sources, bioavailability and dietary variety in age-related macular degeneration protection. Nutrients, 9.","DOI":"10.3390\/nu9020120"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Bianchetti, G., Clementi, M.E., Sampaolese, B., Serantoni, C., Abeltino, A., De Spirito, M., Sasson, S., and Maulucci, G. (2022). Investigation of DHA-induced regulation of redox homeostasis in retinal pigment epithelium cells through the combination of metabolic imaging and molecular biology. Antioxidants, 11.","DOI":"10.3390\/antiox11061072"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Bianchetti, G., Clementi, M.E., Sampaolese, B., Serantoni, C., Abeltino, A., De Spirito, M., Sasson, S., and Maulucci, G. (2023). Metabolic imaging and molecular biology reveal the interplay between lipid metabolism and DHA-induced modulation of redox homeostasis in RPE cells. Antioxidants, 12.","DOI":"10.3390\/antiox12020339"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Group A-REDSR (2013). Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: The Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA, 309, 2005\u20132015.","DOI":"10.1001\/jama.2013.4997"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1016\/j.ophtha.2019.06.004","article-title":"No CFH or ARMS2 interaction with omega-3 fatty acids, low versus high zinc, or \u03b2-carotene versus lutein and zeaxanthin on progression of age-related macular degeneration in the age-related eye disease study 2: Age","volume":"126","author":"Chiu","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.exer.2010.04.012","article-title":"Protection of retinal pigment epithelium by OT-551 and its metabolite TEMPOL-H against light-induced damage in rats","volume":"91","author":"Tanito","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Clementi, M.E., Pizzoferrato, M., Bianchetti, G., Brancato, A., Sampaolese, B., Maulucci, G., and Tringali, G. (2022). Cytoprotective effect of idebenone through modulation of the intrinsic mitochondrial pathway of apoptosis in human retinal pigment epithelial cells exposed to oxidative stress induced by hydrogen peroxide. Biomedicines, 10.","DOI":"10.3390\/biomedicines10020503"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.2147\/OPTH.S194234","article-title":"Therapeutic Potential of the Ranibizumab Port Delivery System in the Treatment of AMD: Evidence to Date","volume":"14","author":"Chen","year":"2020","journal-title":"Clin. Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.2147\/DDDT.S383101","article-title":"Progress and challenges of anti-VEGF agents and their sustained-release strategies for retinal angiogenesis","volume":"16","author":"Xu","year":"2022","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1001\/jamaophthalmol.2020.2685","article-title":"Safety and Efficacy of Different Doses and Regimens of Faricimab vs Ranibizumab in Neovascular Age-Related macular degeneration: The AVENUE phase 2 randomized clinical trial","volume":"138","author":"Rubido","year":"2020","journal-title":"JAMA Ophthalmol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13036-022-00291-y","article-title":"Tissue engineering in age-related macular degeneration: A mini-review","volume":"16","author":"Wu","year":"2022","journal-title":"J. Biol. Eng."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1136\/bjophthalmol-2020-318452","article-title":"Treatments for dry age-related macular degeneration: Therapeutic avenues, clinical trials and future directions","volume":"106","author":"Georgiou","year":"2022","journal-title":"Br. J. Ophthalmol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"100192","DOI":"10.1016\/j.xops.2022.100192","article-title":"Neuroprotection for age-related macular degeneration","volume":"2","author":"Lin","year":"2022","journal-title":"Ophthalmol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1016\/j.ophtha.2018.03.059","article-title":"Emixustat hydrochloride for geographic atrophy secondary to age-related macular degeneration","volume":"125","author":"Rosenfeld","year":"2018","journal-title":"Ophthalmology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11574","DOI":"10.1074\/jbc.RA118.002062","article-title":"A non-retinoid antagonist of retinol-binding protein 4 rescues phenotype in a model of Stargardt disease without inhibiting the visual cycle","volume":"293","author":"Racz","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_44","unstructured":"Saad, L., and Washington, I. (2016). Retinal Degenerative Diseases, Springer International Publishing."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"612402","DOI":"10.3389\/fimmu.2020.612402","article-title":"Monoclonal antibodies capable of inhibiting complement downstream of C5 in multiple species","volume":"11","author":"Zelek","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1001\/jamaophthalmol.2018.1544","article-title":"Efficacy and safety of lampalizumab for geographic atrophy due to age-related macular degeneration: Chroma and spectri phase 3 randomized clinical trials","volume":"136","author":"Holz","year":"2018","journal-title":"JAMA Ophthalmol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.ophtha.2020.08.027","article-title":"C5 inhibitor avacincaptad pegol for geographic atrophy due to age-related macular degeneration: A randomized pivotal phase 2\/3 trial","volume":"128","author":"Jaffe","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.ophtha.2019.07.011","article-title":"Complement C3 inhibitor pegcetacoplan for geographic atrophy secondary to age-related macular degeneration: A randomized phase 2 trial","volume":"127","author":"Liao","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Halawa, O.A., Lin, J.B., Miller, J.W., and Vavvas, D.G. (2021). A review of completed and ongoing complement inhibitor trials for geographic atrophy secondary to age-related macular degeneration. J. Clin. Med., 10.","DOI":"10.3390\/jcm10122580"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1080\/13543784.2020.1763953","article-title":"Risuteganib-a novel integrin inhibitor for the treatment of non-exudative (dry) age-related macular degeneration and diabetic macular edema","volume":"29","author":"Shaw","year":"2020","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"747901","DOI":"10.3389\/fnint.2021.747901","article-title":"Neuroprotective Effects of a Small Mitochondrially-Targeted Tetrapeptide Elamipretide in Neurodegeneration","volume":"15","author":"Nhu","year":"2022","journal-title":"Front. Integr. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/j.oret.2018.03.001","article-title":"A randomized phase 2 study of an anti- amyloid \u03b2 monoclonal antibody in geographic atrophy secondary to age-related macular degeneration","volume":"2","author":"Rosenfeld","year":"2018","journal-title":"Ophthalmol. Retin."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1136\/bjophthalmol-2015-306972","article-title":"Current therapeutic developments in atrophic age-related macular degeneration","volume":"100","author":"Hanus","year":"2016","journal-title":"Br. J. Ophthalmol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"15256","DOI":"10.1074\/jbc.RA118.004008","article-title":"Ciliary neurotrophic factor (CNTF) protects retinal cone and rod photoreceptors by suppressing excessive formation of the visual pigments","volume":"293","author":"Li","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1124\/jpet.120.000483","article-title":"Ocular pharmacokinetics of brimonidine drug delivery system in monkeys and translational modeling for selection of dose and frequency in clinical trials","volume":"378","author":"Tamhane","year":"2021","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Paniagua, M., de la Mata, A., Galindo, S., Bl\u00e1zquez, F., Calonge, M., and Nieto-Miguel, T. (2021). Advanced therapy medicinal products for the eye: Definitions and regulatory framework. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13030347"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"157","DOI":"10.18240\/ijo.2022.01.23","article-title":"Progress of clinical therapies for dry age-related macular degeneration","volume":"15","author":"Rubner","year":"2022","journal-title":"Int. J. Ophthalmol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1093\/stcltm\/szac001","article-title":"Retinal cell transplantation, biomaterials, and in vitro models for developing next-generation therapies of age-related macular degeneration","volume":"11","author":"Rizzolo","year":"2022","journal-title":"Stem Cells Transl. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"588014","DOI":"10.3389\/fbioe.2020.588014","article-title":"Biotechnology and biomaterial-based therapeutic strategies for age-related Macular Degeneration. Part II: Cell and tissue engineering therapies","volume":"8","author":"Guinea","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_60","first-page":"e921184","article-title":"Intravitreal injection of human retinal progenitor cells for treatment of retinal degeneration","volume":"26","author":"Wang","year":"2020","journal-title":"Med. Sci. Monit."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Nair, D.S.R., Seiler, M.J., Patel, K.H., Thomas, V., Camarillo, J.C.M., Humayun, M.S., and Thomas, B.B. (2021). Tissue engineering strategies for retina regeneration. Appl. Sci., 11.","DOI":"10.3390\/app11052154"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"eaao4097","DOI":"10.1126\/scitranslmed.aao4097","article-title":"A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration","volume":"10","author":"Kashani","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s40942-017-0095-6","article-title":"Development of a new tissue injector for subretinal transplantation of human embryonic stem cell derived retinal pigmented epithelium","volume":"3","author":"Fernandes","year":"2017","journal-title":"Int. J. Retin. Vitr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1097\/APO.0000000000000521","article-title":"New prospects for retinal pigment epithelium transplantation","volume":"11","author":"Gullapalli","year":"2022","journal-title":"Asia Pac. J. Ophthalmol."},{"key":"ref_65","unstructured":"(2023, March 24). Safety and Efficacy Study of OpRegen for Treatment of Advanced Dry-Form Age-Related Macular Degeneration, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02286089."},{"key":"ref_66","unstructured":"(2023, March 24). Autologous Transplantation of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium for Geographic Atrophy Associated with Age-Related Macular Degeneration, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04339764."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1186\/s13287-021-02546-9","article-title":"Cell-based therapies for retinal diseases: A review of clinical trials and direct to consumer \u201ccell therapy\u201d clinics","volume":"12","author":"Hinkle","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1186\/s13287-020-01986-z","article-title":"Improving cell survival and engraftment in vivo via layer-by-layer nanocoating of hESC-derived RPE cells","volume":"11","author":"Ru","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"38","DOI":"10.21037\/aes-21-14","article-title":"Novel treatments and genetics of age-related macular degeneration-a narrative review","volume":"6","author":"Arabi","year":"2021","journal-title":"Ann. Eye Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1136\/bjophthalmol-2020-316195","article-title":"Gene therapy for neovascular age-related macular degeneration: Rationale, clinical trials and future directions","volume":"105","author":"Guimaraes","year":"2021","journal-title":"Br. J. Ophthalmol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.tibtech.2015.11.004","article-title":"Overcoming gene-delivery hurdles: Physiological considerations for nonviral vectors","volume":"34","author":"Hill","year":"2016","journal-title":"Trends Biotechnol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"652215","DOI":"10.3389\/fnins.2021.652215","article-title":"Gene therapy to the retina and the cochlea","volume":"15","author":"Crane","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1016\/j.ymthe.2022.03.004","article-title":"Durability of transgene expression after rAAV gene therapy","volume":"30","author":"Muhuri","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_74","unstructured":"(2022). SparingVision\u2019s Lead Product, SPVN06, Is a Breakthrough Gene Therapy Approach Targeting Inherited Retinal Diseases, SpringVision."},{"key":"ref_75","unstructured":"(2023, March 24). AAVCAGsCD59 for the Treatment of Wet AMD, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03585556."},{"key":"ref_76","unstructured":"(2023, March 24). FOCUS: First in Human Study to Evaluate the Safety and Efficacy of GT005 Administered in Subjects with Dry AMD, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03846193."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Becker, J., Fakhiri, J., and Grimm, D. (2022). Fantastic AAV gene therapy vectors and how to find them-random diversification, rational design and machine learning. Pathogens, 11.","DOI":"10.3390\/pathogens11070756"},{"key":"ref_78","first-page":"1","article-title":"Viral vector platforms within the gene therapy landscape","volume":"6","author":"Bulcha","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_79","unstructured":"(2023, March 24). Safety and Tolerability of RPE Stem Cell-Derived RPE(RPESC-RPE) Transplantation in Patients with Dry Age-Related Macular Degeneration (AMD), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04627428."},{"key":"ref_80","unstructured":"(2023, March 24). Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for Eye Diseases, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05147701."},{"key":"ref_81","unstructured":"Regenerative Patch Technologies LLC (2023, March 24). Study of Subretinal Implantation of Human Embryonic Stem Cell-Derived RPE Cells in Advanced Dry AMD. ClinicalTrials.gov Identifier: NCT02590692 Updated. 2020, 29, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02590692."},{"key":"ref_82","unstructured":"(2023, March 24). A Study of Implantation of Retinal Pigment Epithelium in Subjects with Acute Wet Age Related Macular Degeneration, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01691261."},{"key":"ref_83","unstructured":"(2023, March 24). Safety and Efficacy of ADVM-022 in Treatment-Experienced Patients with Neovascular Age-Related Macular Degeneration [LUNA], Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05536973."},{"key":"ref_84","unstructured":"(2023, March 24). Gene Therapy for Wet AMD, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05611424."},{"key":"ref_85","unstructured":"(2023, March 24). 4D-150 in Patients With Neovascular (Wet) Age-Related Macular Degeneration, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05197270."},{"key":"ref_86","unstructured":"(2023, March 24). VEGFA-Targeting Gene Therapy to Treat Retinal and Choroidal Neovascularization Diseases, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05099094."},{"key":"ref_87","unstructured":"(2023, March 24). RGX-314 Gene Therapy Pharmacodynamic Study for Neovascular Age-related Macular Degeneration (nAMD), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04832724."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.ymthe.2017.11.019","article-title":"Triple vectors expand AAV transfer capacity in the retina","volume":"26","author":"Maddalena","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1098\/rsif.2006.0124","article-title":"Challenges in tissue engineering","volume":"3","author":"Ikada","year":"2006","journal-title":"J. R. Soc. Interface"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1007\/s40778-016-0039-3","article-title":"Engineering biomaterials for enhanced tissue regeneration","volume":"2","author":"Abbott","year":"2016","journal-title":"Curr. Stem Cell Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.bioactmat.2019.10.005","article-title":"Recent advances in biomaterials for 3D scaffolds: A review","volume":"4","author":"Nikolova","year":"2019","journal-title":"Bioact. Mater."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"BECB.S10961","DOI":"10.4137\/BECB.S10961","article-title":"Design strategies of biodegradable scaffolds for tissue regeneration","volume":"6","author":"Bitar","year":"2014","journal-title":"Biomed. Eng. Comput. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0142-9612(96)85753-X","article-title":"Tissue engineering scaffolds using superstructures","volume":"17","author":"Wintermantel","year":"1996","journal-title":"Biomaterials"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0169-409X(98)00023-4","article-title":"Host response to tissue engineered devices","volume":"33","author":"Mikos","year":"1998","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1016\/j.biomaterials.2008.11.040","article-title":"Macrophage phenotype and remodeling outcomes in response to biologic scaffolds with and without a cellular component","volume":"30","author":"Brown","year":"2009","journal-title":"Biomaterials"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Bonferoni, M.C., Caramella, C., Catenacci, L., Conti, B., Dorati, R., Ferrari, F., Genta, I., Modena, T., Perteghella, S., and Rossi, S. (2021). Biomaterials for soft tissue repair and regeneration: A focus on Italian research in the field. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13091341"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"188","DOI":"10.3389\/fbioe.2020.00188","article-title":"Angiogenesis in Tissue Engineering: As Nature Intended?","volume":"8","author":"Mastrullo","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2041731417720841","DOI":"10.1177\/2041731417720841","article-title":"Scaffolds for retinal pigment epithelial cell transplantation in age-related macular degeneration","volume":"8","author":"White","year":"2017","journal-title":"J. Tissue Eng."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s10616-015-9895-4","article-title":"Scaffolds and cells for tissue regeneration: Different scaffold pore sizes-different cell effects","volume":"68","author":"Bagdonas","year":"2016","journal-title":"Cytotechnology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"731031","DOI":"10.3389\/fsurg.2021.731031","article-title":"Regenerative engineering: Current applications and future perspectives","volume":"8","author":"Goldenberg","year":"2021","journal-title":"Front. Surg."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Reddy, M.S.B., Ponnamma, D., Choudhary, R., and Sadasivuni, K.K. (2021). A comparative review of natural and synthetic biopolymer composite scaffolds. Polymers, 13.","DOI":"10.3390\/polym13071105"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Lin, K.T., Wang, A., Nguyen, A.B., Iyer, J., and Tran, S.D. (2021). Recent advances in hydrogels: Ophthalmic applications in cell delivery, vitreous substitutes, and ocular adhesives. Biomedicines, 9.","DOI":"10.3390\/biomedicines9091203"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Parisi, L., Toffoli, A., Ghiacci, G., and Macaluso, G.M. (2018). Tailoring the interface of biomaterials to design effective scaffolds. J. Funct. Biomater., 9.","DOI":"10.3390\/jfb9030050"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Krishani, M., Shin, W.Y., Suhaimi, H., and Sambudi, N.S. (2023). Development of scaffolds from bio-based natural materials for tissue regeneration applications: A review. Gels, 9.","DOI":"10.3390\/gels9020100"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"5298","DOI":"10.1021\/acs.chemrev.8b00593","article-title":"Electrospinning and electrospun nanofibers: Methods, materials, and applications","volume":"119","author":"Xue","year":"2019","journal-title":"Chem. Rev."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Hong, J., Yeo, M., Yang, G.H., and Kim, G. (2019). Cell-electrospinning and its application for tissue engineering. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246208"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.progpolymsci.2010.03.003","article-title":"Polymer nanofibrous structures: Fabrication, biofunctionalization, and cell interactions","volume":"35","author":"Beachley","year":"2010","journal-title":"Prog. Polym. Sci."},{"key":"ref_108","unstructured":"Zhang, L., Leong, K., and Fisher, J. (2022). 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine, Academic Press."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.addr.2021.05.007","article-title":"Pharmaceutical electrospinning and 3D printing scaffold design for bone regeneration","volume":"174","author":"Wang","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2010609","DOI":"10.1002\/adfm.202010609","article-title":"Scaffold fabrication technologies and structure\/function properties in bone tissue engineering","volume":"31","author":"Collins","year":"2021","journal-title":"Adv. Funct. Mater."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1615\/CritRevTherDrugCarrierSyst.v29.i1.10","article-title":"Scaffold: A novel carrier for cell and drug delivery","volume":"29","author":"Garg","year":"2012","journal-title":"Crit. Rev. Ther. Drug Carr. Syst."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Capuana, E., Lopresti, F., Carf\u00ec Pavia, F., Brucato, V., and La Carrubba, V. (2021). Solution-based processing for scaffold fabrication in tissue engineering applications: A brief review. Polymers, 13.","DOI":"10.3390\/polym13132041"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40824-022-00338-7","article-title":"Emerging 3D bioprinting applications in plastic surgery","volume":"27","author":"Yang","year":"2023","journal-title":"Biomater. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"824156","DOI":"10.3389\/fbioe.2022.824156","article-title":"3D bioprinted scaffolds for bone tissue engineering: State-of-the-art and emerging technologies","volume":"10","author":"Yazdanpanah","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.ajps.2019.11.003","article-title":"Development of 3D bioprinting: From printing methods to biomedical applications","volume":"15","author":"Gu","year":"2020","journal-title":"Asian J. Pharm. Sci."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/4\/620\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:19:31Z","timestamp":1760123971000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/4\/620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,20]]},"references-count":115,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ph16040620"],"URL":"https:\/\/doi.org\/10.3390\/ph16040620","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,20]]}}}