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Eye","award":["S-EURONANOMED-19-1\/LSS-600000-2063"],"award-info":[{"award-number":["S-EURONANOMED-19-1\/LSS-600000-2063"]}]},{"name":"Canada Research Chair Tier 1 in Biomaterials and Stem Cells in Ophthalmology and a Caroline Durand Foundation Research Chair in Cellular Therapy in the Eye","award":["RGPIN-2017-05410"],"award-info":[{"award-number":["RGPIN-2017-05410"]}]},{"name":"Canada Research Chair Tier 1 in Biomaterials and Stem Cells in Ophthalmology and a Caroline Durand Foundation Research Chair in Cellular Therapy in the Eye","award":["MR\/T030968\/1"],"award-info":[{"award-number":["MR\/T030968\/1"]}]},{"name":"Canada Research Chair Tier 1 in Biomaterials and Stem Cells in Ophthalmology and a Caroline Durand Foundation Research Chair in Cellular Therapy in the Eye","award":["#K99EY031373"],"award-info":[{"award-number":["#K99EY031373"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Severe HSV-1 infection can cause blindness due to tissue damage from severe inflammation. Due to the high risk of graft failure in HSV-1-infected individuals, cornea transplantation to restore vision is often contraindicated. We tested the capacity for cell-free biosynthetic implants made from recombinant human collagen type III and 2-methacryloyloxyethyl phosphorylcholine (RHCIII-MPC) to suppress inflammation and promote tissue regeneration in the damaged corneas. To block viral reactivation, we incorporated silica dioxide nanoparticles releasing KR12, the small bioactive core fragment of LL37, an innate cationic host defense peptide produced by corneal cells. KR12 is more reactive and smaller than LL37, so more KR12 molecules can be incorporated into nanoparticles for delivery. Unlike LL37, which was cytotoxic, KR12 was cell-friendly and showed little cytotoxicity at doses that blocked HSV-1 activity in vitro, instead enabling rapid wound closure in cultures of human epithelial cells. Composite implants released KR12 for up to 3 weeks in vitro. The implant was also tested in vivo on HSV-1-infected rabbit corneas where it was grafted by anterior lamellar keratoplasty. Adding KR12 to RHCIII-MPC did not reduce HSV-1 viral loads or the inflammation resulting in neovascularization. Nevertheless, the composite implants reduced viral spread sufficiently to allow stable corneal epithelium, stroma, and nerve regeneration over a 6-month observation period.<\/jats:p>","DOI":"10.3390\/pharmaceutics15061658","type":"journal-article","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T04:34:51Z","timestamp":1685939691000},"page":"1658","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Phosphorylcholine and KR12-Containing Corneal Implants in HSV-1-Infected Rabbit Corneas"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3701-4951","authenticated-orcid":false,"given":"Kamal","family":"Malhotra","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3C 3J7, Canada"},{"name":"Maisonneuve-Rosemont Hospital Research Centre, Montreal, QC H1T 2M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5534-6258","authenticated-orcid":false,"given":"Oleksiy","family":"Buznyk","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Link\u00f6ping University, 58183 Link\u00f6ping, Sweden"},{"name":"Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine, 65061 Odessa, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Mirazul","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Link\u00f6ping University, 58183 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elle","family":"Edin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3C 3J7, Canada"},{"name":"Maisonneuve-Rosemont Hospital Research Centre, Montreal, QC H1T 2M4, Canada"},{"name":"Department of Clinical and Experimental Medicine, Link\u00f6ping University, 58183 Link\u00f6ping, Sweden"},{"name":"Institute of Biomedical Engineering, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sankar","family":"Basu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Asutosh College, Affiliated with University of Calcutta, Kolkata 700026, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Groleau","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3C 3J7, Canada"},{"name":"Maisonneuve-Rosemont Hospital Research Centre, Montreal, QC H1T 2M4, Canada"},{"name":"D\u00e9partement de Microbiologie, Infectiologie et Immunologie, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delali Shana","family":"D\u00e9gu\u00e9","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3C 3J7, Canada"},{"name":"Maisonneuve-Rosemont Hospital Research Centre, Montreal, QC H1T 2M4, Canada"},{"name":"Institute of Biomedical Engineering, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Fagerholm","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Link\u00f6ping University, 58183 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrien","family":"Fois","sequence":"additional","affiliation":[{"name":"Maisonneuve-Rosemont Hospital Research Centre, Montreal, QC H1T 2M4, Canada"},{"name":"D\u00e9partement de Microbiologie, Infectiologie et Immunologie, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Lesage","sequence":"additional","affiliation":[{"name":"Maisonneuve-Rosemont Hospital Research Centre, Montreal, QC H1T 2M4, Canada"},{"name":"D\u00e9partement de Microbiologie, Infectiologie et Immunologie, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaganmohan R.","family":"Jangamreddy","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Link\u00f6ping University, 58183 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5440-3591","authenticated-orcid":false,"given":"Egidijus","family":"\u0160imoli\u016bnas","sequence":"additional","affiliation":[{"name":"Department of Biological Models, Institute of Biochemistry, Life Sciences Center, Vilnius University, 01513 Vilnius, Lithuania"}],"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 Clinical and Experimental Medicine, Link\u00f6ping University, 58183 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6142-5489","authenticated-orcid":false,"given":"Hirak K.","family":"Patra","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Link\u00f6ping University, 58183 Link\u00f6ping, Sweden"},{"name":"Department of Surgical Biotechnology, UCL Division of Surgery and Interventional Science, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May","family":"Griffith","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3C 3J7, Canada"},{"name":"Maisonneuve-Rosemont Hospital Research Centre, Montreal, QC H1T 2M4, Canada"},{"name":"Department of Clinical and Experimental Medicine, Link\u00f6ping University, 58183 Link\u00f6ping, Sweden"},{"name":"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":[[2023,6,5]]},"reference":[{"key":"ref_1","unstructured":"Copeland, R.A. 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