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Human donor corneal transplantation remains the primary treatment for scarred corneas resulting from herpes simplex keratitis (HSK), a severe inflammatory corneal disease caused by HSV-1 infection, despite a high risk of re-infection or immune rejection of the allografts. As possible alternatives to donor grafting for HSK, we developed cell-free, regeneration-stimulating corneal implants designed to work even under adverse inflammatory situations such as severe infections. The implants comprised short, fully synthetic collagen-like peptides conjugated to polyethylene glycol (CLP-PEG) and crosslinked using carbodiimide chemistry. Being cell-free, they lacked the cellular targets that an already activated immune system would encounter in these inflamed corneas. We tested the performance of these implants in guinea pig and rabbit models of HSK. Three different HSV-1 strains were used to create experimental HSK in rabbits and guinea pigs. There were no overall statistically significant species differences or species\u2013strain differences in virus-induced mortality. At three months post-operation, all treated corneas showed tissue regeneration, but with haze or neovascularization. The initially cell-free CLP-PEG implants allowed for repopulation by ingrowing cells to regenerate neocorneal tissue, despite the inflammation. However, they did not prevent HSV-1 reactivation nor re-infection, as neovascularization and disorganization were observed within the neocorneas. A detailed histopathological examination revealed viral strain differences, but only KOS infection showed interspecies neovascularization differences. A more detailed examination with larger numbers of animals is merited to fully elucidate the effects of the different viral strains on rabbits versus guinea pigs.<\/jats:p>","DOI":"10.3390\/jfb16100377","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T10:35:36Z","timestamp":1760006136000},"page":"377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Collagen Analogs Promote Tissue Regeneration in HSV-1-Infected Corneas in Animal Models"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5534-6258","authenticated-orcid":false,"given":"Oleksiy","family":"Buznyk","sequence":"first","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, Link\u00f6ping University, SE-581 83 Link\u00f6ping, Sweden"},{"name":"Department of Ophthalmology, Link\u00f6ping University, SE-581 85 Link\u00f6ping, Sweden"},{"name":"Filatov Institute of Eye Diseases & Tissue Therapy of the NAMS of Ukraine, 65015 Odessa, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid","family":"Goodarzi","sequence":"additional","affiliation":[{"name":"Maisonneuve-Rosemont Hospital Research Centre (CRHMR), Montreal, QC H1T 2H2, Canada"},{"name":"Department of Ophthalmology and Institute of Biomedical Engineering, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1787-5642","authenticated-orcid":false,"given":"Jaime","family":"G\u00f3mez Laguna","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Comparative Pathology and Toxicology, Pathology and Immunology Group (UCO-PIG), UIC Zoonosis y Enfermedades Emergentes ENZOEM, International Excellence Agrifood Campus \u2018CeiA3\u2019, University of C\u00f3rdoba, 14014 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaganmohan","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, Link\u00f6ping University, SE-581 83 Link\u00f6ping, Sweden"},{"name":"UR Advanced Therapeutics, Hyderabad 501203, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7252-6736","authenticated-orcid":false,"given":"Aneta","family":"Liszka","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, Link\u00f6ping University, SE-581 83 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8465-1764","authenticated-orcid":false,"given":"Elle","family":"Edin","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, Link\u00f6ping University, SE-581 83 Link\u00f6ping, Sweden"},{"name":"Maisonneuve-Rosemont Hospital Research Centre (CRHMR), Montreal, QC H1T 2H2, Canada"},{"name":"Department of Ophthalmology and Institute of Biomedical Engineering, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3892-8483","authenticated-orcid":false,"given":"Christos","family":"Boutopoulos","sequence":"additional","affiliation":[{"name":"Maisonneuve-Rosemont Hospital Research Centre (CRHMR), Montreal, QC H1T 2H2, Canada"},{"name":"Department of Ophthalmology and Institute of Biomedical Engineering, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Chodosh","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of New Mexico, Albuquerque, NM 87106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Mirazul","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of New Mexico, Albuquerque, NM 87106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1222-6720","authenticated-orcid":false,"given":"May","family":"Griffith","sequence":"additional","affiliation":[{"name":"Maisonneuve-Rosemont Hospital Research Centre (CRHMR), Montreal, QC H1T 2H2, Canada"},{"name":"Department of Ophthalmology and Institute of Biomedical Engineering, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eabq0997","DOI":"10.1126\/sciadv.abq0997","article-title":"Global Trends in Clinical Trials Involving Engineered Biomaterials","volume":"10","author":"Lele","year":"2024","journal-title":"Sci. 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