Porcine Corneal Models as Translational Platforms for Innovative Therapies: Current Insights and Future Directions
Source abstract
Abstract
The development of advanced biomaterials for corneal applications requires robust translational platforms that faithfully replicate human characteristics. Porcine corneas are increasingly recognized for ophthalmic research. Their unique combination of anatomical similarity, biomechanical comparability, and accessibility make them highly suitable for preclinical evaluation of innovative therapies, bridging the gap between preclinical discovery and clinical application. This review outlines the utility of porcine corneal models in validating advanced biomaterials, particularly in ex vivo settings, focusing on current methodologies, while addressing challenges and future directions. We aim to underscore the potential of porcine corneal models to accelerate the translation of next-generation biomaterials into clinically relevant corneal therapies.
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Research context
OpenAlex topics: Corneal Surgery and Treatments · Corneal surgery and disorders · Ocular Surface and Contact Lens
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Physics, Faculty of Sciences and Technology, University of Coimbra, R. Larga, 3004-516 Coimbra, Portugal
Chemical Engineering and Renewable Resources for Sustainability (CEReS), Department of Chemical Engineering, University of Coimbra, R. Sílvio Lima, 3030-790 Coimbra, Portugal
Laboratory of Physics for Materials and Emerging Technologies (LaPMET), Center of Physics and Engineering of Advanced Materials (CeFEMA), Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
Center for Neuroscience and Cell Biology, University of Coimbra, R. Larga, 3004-504 Coimbra, Portugal
Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, R. Larga, 3004-504 Coimbra, Portugal
Funding
Fundação para a Ciência e Tecnologia
References (100+)
Show source-provided references
1. (2025, November 25). IAPB Vision Atlas. Available online: https://visionatlas.iapb.org/.
2. Next-Generation Smart Ophthalmic Biomaterials: From Passive Response to Active Interaction and Closed-Loop Control
3. Tan, J., Foster, L.J.R., Lovicu, F.J., Ramaswamy, Y., Singh, G., and Watson, S.L. (2025). Corneal Sealants in Pre-Clinical Development. Curr. Eye Res., 1–16.10.1080/02713683.2025.2566853 ↗
4. Hu, Z., He, X., Teng, L., Zeng, X., Zhu, S., Dong, Y., Zeng, Z., Zheng, Q., and Sun, X. (2025). Adhesion Mechanism, Applications, and Challenges of Ocular Tissue Adhesives. Int. J. Mol. Sci., 26.10.3390/ijms26020486 ↗
5. Photo Cross-Linkable Biopolymers for Cornea Tissue Healing10.2174/1574888X16666210715112738 ↗
6. Yuan, Y., Lim, K.S., Sutton, G., Wallace, G.G., and You, J. (2025). 3D Printing Strategies for Bioengineering Human Cornea. Adv. Healthc. Mater., e02767, Early View.10.1002/adhm.202502767 ↗
7. Silk Biomaterials for Corneal Tissue Engineering: From Research Approaches to Therapeutic Potentials; A Review10.1016/j.ijbiomac.2025.141039 ↗
8. Biomaterials for Corneal Regeneration
9. 3D Bioprinting of Corneal Models: A Review of the Current State and Future Outlook10.1177/20417314231197793 ↗
10. Biologicals and Biomaterials for Corneal Regeneration and Vision Restoration in Limbal Stem Cell Deficiency10.1002/adma.202401763 ↗
11. Bringing Ophthalmology into the Scientific World: Novel Nanoparticle-Based Strategies for Ocular Drug Delivery10.1016/j.jtos.2025.03.004 ↗
12. An Insight on Ophthalmic Drug Delivery Systems: Focus on Polymeric Biomaterials-Based Carriers10.1016/j.jconrel.2023.08.041 ↗
13. Microneedles for Controlled and Sustained Intraocular Drug Delivery10.1038/s41427-025-00614-7 ↗
14. Rykowska, I., Nowak, I., Nowak, R., and Michałkiewicz, O. (2025). Biodegradable Contact Lenses for Targeted Ocular Drug Delivery: Recent Advances, Clinical Applications, and Translational Perspectives. Molecules, 30.10.3390/molecules30122542 ↗
15. Therapeutic Applications of Contact Lens-Based Drug Delivery Systems in Ophthalmic Diseases10.1080/10717544.2023.2219419 ↗
16. Advancements and Applications of Smart Contact Lenses: A Comprehensive Review10.1016/j.rineng.2024.103268 ↗
17. Li, J.Y., Li, J.B., Song, H., Huan, H.J., Wang, X.L., Zhao, Y.P., Ma, H.Z., and Wang, Y. (2025). Smart Contact Lenses: Recent Advances and Future Challenges in Eye Disease Diagnosis and Treatment. Graefes Arch. Clin. Exp. Ophthalmol.10.1007/s00417-025-06978-4 ↗
18. Biosensor-Embedded Wearables for Dry Eye Monitoring and Management10.1080/17434440.2025.2555485 ↗
19. Enhancing Glaucoma Care with Smart Contact Lenses: An Overview of Recent Developments10.1007/s10544-025-00740-7 ↗
20. Neuro Receptor Signal Detecting and Monitoring Smart Devices for Biological Changes in Cognitive Health Conditions10.1177/09727531231206888 ↗
21. Tear-Based Glucose Monitoring: A Non-Invasive Approach to Diabetes Control in Resource-Limited Settings10.1016/j.bios.2025.118209 ↗
22. American Academy of Ophthalmology (2024). Fundamentals and Principles of Ophthalmology, American Academy of Ophthalmology.
23. Remington, L.A. (2012). Visual System. Clinical Anatomy and Physiology of the Visual System, Elsevier.10.1016/B978-1-4377-1926-0.10001-3 ↗
24. Remington, L.A. (2012). Cornea and Sclera. Clinical Anatomy and Physiology of the Visual System, Elsevier.10.1016/B978-1-4377-1926-0.10002-5 ↗
25. Guérin, L.P., Le-Bel, G., Desjardins, P., Couture, C., Gillard, E., Boisselier, É., Bazin, R., Germain, L., and Guérin, S.L. (2021). The Human Tissue-Engineered Cornea (HTEC): Recent Progress. Int. J. Mol. Sci., 22.10.3390/ijms22031291 ↗
26. Biomaterials for Corneal Bioengineering10.1088/1748-605X/aa92d2 ↗
27. Corneal Laceration Associated with Upper Eyelid Blepharoplasty10.1097/IOP.0000000000001509 ↗
28. Chandran, C., Santra, M., Rubin, E., Geary, M.L., and Yam, G.H.F. (2024). Regenerative Therapy for Corneal Scarring Disorders. Biomedicines, 12.10.3390/biomedicines12030649 ↗
29. Research Progress of Corneal Endothelial Cell Regeneration and Replacement10.1002/eer3.2 ↗
30. Nanotechnology-Based Ocular Drug Delivery Systems: Recent Advances and Future Prospects10.1186/s12951-023-01992-2 ↗
31. Barrier Function in the Ocular Surface: From Conventional Paradigms to New Opportunities10.1016/j.jtos.2014.10.003 ↗
32. Loiseau, A., Raîche-Marcoux, G., Maranda, C., Bertrand, N., and Boisselier, E. (2023). Animal Models in Eye Research: Focus on Corneal Pathologies. Int. J. Mol. Sci., 24.10.3390/ijms242316661 ↗
33. Zeb1 Facilitates Corneal Epithelial Wound Healing by Maintaining Corneal Epithelial Cell Viability and Mobility10.1038/s42003-023-04831-0 ↗
34. A New Corneal Epithelial Biomimetic 3D Model for in Vitro Eye Toxicity Assessment: Development, Characterization and Applicability10.1016/j.tiv.2019.104666 ↗
35. New Human Organotypic Corneal Tissue Model for Ophthalmic Drug Delivery Studies10.1167/iovs.18-23944 ↗
36. 3D in Vitro Corneal Models: A Review of Current Technologies10.1016/j.exer.2020.108213 ↗
37. Bandeira, F., Grottone, G.T., Covre, J.L., Cristovam, P.C., Loureiro, R.R., Pinheiro, F.I., Casaroli-Marano, R.P., Donato, W., and Gomes, J.Á.P. (2023). A Framework for Human Corneal Endothelial Cell Culture and Preliminary Wound Model Experiments with a New Cell Tracking Approach. Int. J. Mol. Sci., 24.10.3390/ijms24032982 ↗
38. Bioinspired Hydrogel Surfaces to Augment Corneal Endothelial Cell Monolayer Formation10.1002/term.3173 ↗
39. Investigating the Role of Molecular Coating in Human Corneal Endothelial Cell Primary Culture Using Artificial Intelligence-Driven Image Analysis10.1038/s41598-025-14367-4 ↗
40. Namli, I., Gupta, D., Singh, Y.P., Datta, P., Rizwan, M., Baykara, M., and Ozbolat, I.T. (2025). Progressive Insights into 3D Bioprinting for Corneal Tissue Restoration. Adv. Healthc. Mater., e03372. Early View.10.1002/adhm.202503372 ↗
41. Comprehensive Review of the State-of-the-Art in Corneal 3D Bioprinting, Including Regulatory Aspects10.1016/j.ijpharm.2024.124510 ↗
42. Current and Future Cornea Chip Models for Advancing Ophthalmic Research and Therapeutics10.1002/adbi.202400571 ↗
43. A Biomimetic Human Disease Model of Bacterial Keratitis Using a Cornea-on-a-Chip System10.1039/D4BM00833B ↗
44. Modeling Dry Eye with an Air-Liquid Interface in Corneal Epithelium-on-a-Chip10.1038/s41598-024-54736-z ↗
45. In Vitro and Ex Vivo Models for Assessing Drug Permeation across the Cornea10.1021/acs.molpharmaceut.3c00195 ↗
46. Ex Vivo Applications of Porcine Ocular Surface Tissues: Advancing Eye Research and Alternatives to Animal Studies
47. Barbalho, G.N., Falcão, M.A., Lopes, J.M.S., Lopes, J.M., Contarato, J.L.A., Gelfuso, G.M., Cunha-Filho, M., and Gratieri, T. (2023). Dynamic Ex Vivo Porcine Eye Model to Measure Ophthalmic Drug Penetration under Simulated Lacrimal Flow. Pharmaceutics, 15.10.3390/pharmaceutics15092325 ↗
48. Development of a Convenient Ex Vivo Model for the Study of the Transcorneal Permeation of Drugs: Histological and Permeability Evaluation10.1002/jps.24231 ↗
49. Shi, M.-D., Sung, K.-C., Huang, J.-M., Chen, C.-H., Wang, Y.-J., Shi, M.-D., Sung, K.-C., Huang, J.-M., Chen, C.-H., and Wang, Y.-J. (2024). Development of an Ex Vivo Porcine Eye Model for Exploring the Pathogenicity of Acanthamoeba. Microorganisms, 12.10.3390/microorganisms12061161 ↗
50. Establishing a Porcine Ex Vivo Cornea Model for Studying Drug Treatments against Bacterial Keratitis
51. Establishment of an Ex Vivo Human Corneal Endothelium Wound Model10.1167/tvst.14.1.24 ↗
52. Ex Vivo Corneal Organ Culture Model for Wound Healing Studies
53. Netto, A.R.T., Hurst, J., Bartz-Schmidt, K.-U., Schnichels, S., Rocha, A., Netto, T., Hurst, J., Bartz-Schmidt, K.-U., and Schnichels, S. (2022). Porcine Corneas Incubated at Low Humidity Present Characteristic Features Found in Dry Eye Disease. Int. J. Mol. Sci., 23.10.3390/ijms23094567 ↗
54. New Ex Vivo Model of Corneal Endothelial Phacoemulsification Injury and Rescue Therapy with Mesenchymal Stromal Cell Secretome10.1016/j.jcrs.2018.09.030 ↗
55. Development of a Novel Ex Vivo Model for Chemical Ocular Toxicity Assessment and Its Applicability for Hair Straightening Products10.1016/j.fct.2022.113457 ↗
56. Development and in Vitro and Ex Vivo Characterization of a Twin Nanoparticulate System to Enhance Ocular Absorption and Prolong Retention of Dexamethasone in the Eye: From Lab to Pilot Scale Optimization10.1039/D4NA01086H ↗
57. Evaluation of 2 Ex Vivo Bovine Cornea Storage Protocols for Drug Delivery Applications10.1159/000493488 ↗
58. The Importance of Donor Characteristics, Post-Mortem Time and Preservation Time for Use and Efficacy of Donated Corneas for Posterior Lamellar Keratoplasty10.1111/aos.14943 ↗
59. Bowman’s Layer in the Cornea–Structure and Function and Regeneration10.1016/j.exer.2020.108033 ↗
60. Species Differences in the Geometry of the Anterior Segment Differentially Affect Anterior Chamber Cell Scoring Systems in Laboratory Animals10.1089/jop.2015.0071 ↗
61. Vézina, M. (2012). Comparative Ocular Anatomy in Commonly Used Laboratory Animals. Molecular and Integrative Toxicology, Springer.10.1007/978-1-62703-164-6_1 ↗
62. Comparative Observations on Corneas, with Special Reference to Bowman’s Layer and Descemet’s Membrane in Mammals and Amphibians10.1002/jmor.10030 ↗
63. The Parameters of the Porcine Eyeball10.1007/s00417-011-1617-9 ↗
64. The Microanatomy of Bowman’s Layer in the Cornea of the Pig: Changes in Collagen Fibril Architecture at the Corneoscleral Limbus
65. Retina in a Dish: Cell Cultures, Retinal Explants and Animal Models for Common Diseases of the Retina10.1016/j.preteyeres.2020.100880 ↗
66. Sustained Ocular Delivery of Bevacizumab Using Densomeres in Rabbits: Effects on Molecular Integrity and Bioactivity10.1167/tvst.12.3.28 ↗
67. Comparison of In Vitro Corneal Permeation and In Vivo Ocular Bioavailability in Rabbits of Three Marketed Latanoprost Formulations10.1007/s13318-023-00853-5 ↗
68. Chen, Q., Gao, N., and Yu, F.S. (2023). Interleukin-36 Receptor Signaling Attenuates Epithelial Wound Healing in C57BL/6 Mouse Corneas. Cells, 12.10.3390/cells12121587 ↗
69. Twelve-Month Clinical and Histopathological Performance of a Novel Synthetic Cornea Device in Rabbit Model10.1167/tvst.12.8.9 ↗
70. A Rabbit Corneal Endothelial Dysfunction Model Using Endothelial-Mesenchymal Transformed Cells10.1038/s41598-018-35110-2 ↗
71. Sun, F., Xi, L.W.Q., Luu, W., Enkhbat, M., Neo, D., Mehta, J.S., Peh, G.S.L., and Yim, E.K.F. (2025). Preclinical Models for Studying Fuchs Endothelial Corneal Dystrophy. Cells, 14.10.3390/cells14070505 ↗
72. Development and Validation of a Deep Learning Model for Diagnosing Neuropathic Corneal Pain via in Vivo Confocal Microscopy10.1038/s41746-025-01577-3 ↗
73. Ethical Considerations Regarding Animal Experimentation
74. Ocular Translational Science: A Review of Development Steps and Paths10.1016/j.addr.2018.01.012 ↗
75. Characterisation of the Porcine Eyeball as an In-Vitro Model for Dry Eye10.1016/j.clae.2017.09.003 ↗
76. Crespo-Moral, M., García-Posadas, L., López-García, A., and Diebold, Y. (2020). Histological and Immunohistochemical Characterization of the Porcine Ocular Surface. PLoS ONE, 15.10.1371/journal.pone.0227732 ↗
77. Porcine Ophthalmology10.1016/j.cvfa.2010.09.002 ↗
78. Corneal Xenotransplantation: Where Are We Standing? Prog
79. In Vitro and Ex Vivo Models to Study Drug Delivery Barriers in the Posterior Segment of the Eye10.1016/j.addr.2017.09.007 ↗
80. Training Strategies and Outcomes of Ab Interno Trabeculectomy with the Trabectome10.12688/f1000research.10236.1 ↗
81. Comparison of the Pig and Feline Models for Full Thickness Corneal Transplantation10.1111/j.1463-5224.2011.00886.x ↗
82. Foja, S., Heinzelmann, J., Hünniger, S., Viestenz, A., Rüger, C., and Viestenz, A. (2024). Drug-Dependent Inhibitory Effects on Corneal Epithelium Structure, Cell Viability, and Corneal Wound Healing by Local Anesthetics. Int. J. Mol. Sci., 25.10.3390/ijms252313074 ↗
83. Viability of Porcine Corneal Epithelium Ex Vivo and Effect of Exposure to Air: A Pilot Study for a Dry Eye Model10.1097/01.ico.0000127475.29551.56 ↗
84. Corneal Epithelial Cell Viability of an Ex Vivo Porcine Eye Model10.1111/cxo.12128 ↗
85. Porcine Cornea Storage Ex Vivo Model as an Alternative to Human Donor Tissues for Investigations of Endothelial Layer Preservation10.1167/tvst.12.4.24 ↗
86. Corneal Crosslinking with Genipin, Comparison with UV-Riboflavin in Ex-Vivo Model
87. Kim, K.W., Shin, Y.J., and Lee, S.C.S. (2022). Novel ROCK Inhibitors, Sovesudil and PHP-0961, Enhance Proliferation, Adhesion and Migration of Corneal Endothelial Cells. Int. J. Mol. Sci., 23.10.3390/ijms232314690 ↗
88. Confocal Imaging of the Keratocyte Network in Porcine Cornea Using the Fixable Vital Dye 5-Chloromethylfluorescein Diacetate10.3109/02713689608997410 ↗
89. Ex Vivo Permeation of Erythropoietin through Porcine Conjunctiva, Cornea, and Sclera10.1007/s13346-017-0399-y ↗
90. Corneal and Scleral Permeability of Desmoteplase in Different Species10.1111/vop.12782 ↗
91. Gómez-Segura, L., Parra, A., Calpena, A.C., Gimeno, Á., and Boix-Montañes, A. (2020). Carprofen Permeation Test through Porcine Ex Vivo Mucous Membranes and Ophthalmic Tissues for Tolerability Assessments: Validation and Histological Study. Vet. Sci., 7.10.3390/vetsci7040152 ↗
92. Ciprofloxacin Self-Dissolvable Soluplus Based Polymeric Films: A Novel Proposal to Improve the Management of Eye Infections10.1007/s13346-020-00887-1 ↗
93. Enhancement of Corneal Permeation of Riboflavin-5′-Phosphate through Vitamin E TPGS: A Promising Approach in Corneal Trans-Epithelial Cross Linking Treatment10.1016/j.ijpharm.2012.09.051 ↗
94. A Proposed Eye Ex Vivo Permeation Approach to Evaluate Pesticides: Case Dimethoate10.1016/j.tiv.2020.104833 ↗
95. Bhujbal, S., Rupenthal, I.D., and Agarwal, P. (Drug Deliv. Transl. Res., 2025). Evaluation of Ocular Tolerability and Bioavailability of Tonabersat Transfersomes Ex Vivo, Drug Deliv. Transl. Res., online ahead of print.10.1007/s13346-025-01872-2 ↗
96. Permeation Dynamics of Organic Moiety-Tuned Organosilica Nanoparticles across Porcine Corneal Barriers: Experimental and Mass Transfer Analysis for Glaucoma Drug Delivery10.1088/2057-1976/ade0c3 ↗
97. Rapid Assessment of Ocular Drug Delivery in a Novel Ex Vivo Corneal Model10.1038/s41598-020-68254-1 ↗
98. The Biochemical, Biological, and Pathological Kaleidoscope of Cell Surface Substrates Processed by Matrix Metalloproteinases10.1080/10409230701340019 ↗
99. Chen, W., Li, Z., Hu, J., Zhang, Z., Chen, L., Chen, Y., and Liu, Z. (2011). Corneal Alternations Induced by Topical Application of Benzalkonium Chloride in Rabbit. PLoS ONE, 6.10.1371/journal.pone.0026103 ↗
100. Study of Penetration Mechanism of Labrasol on Rabbit Cornea by Ussing Chamber, RT-PCR Assay, Western Blot and Immunohistochemistry