{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:48:05Z","timestamp":1760240885421,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T00:00:00Z","timestamp":1569542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY029055"],"award-info":[{"award-number":["R01EY029055"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"KKESH-WEI","award":["03-04 grant"],"award-info":[{"award-number":["03-04 grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Purpose: To investigate the impact of tissue derived biological particles on enzyme-mediated weakened corneas. Methods: Rabbit corneas were treated with enzymes to create an ex vivo ectatic model that simulated representative characteristics of keratoconus (KC). Porcine cornea, cartilage, and lymph node tissues were processed to remove most cellular components and cryomilled into microparticles. The KC corneas were cultured in medium containing the tissue-derived biological particles (TDP) overnight. The mechanical, thermal, ultrastructural changes, and gene expressions of corneal stromal cells were characterized to evaluate the effects of the TDP treatment. Results: The enzyme treatment significantly reduced corneal mechanics and thermal stability, and also disrupted the extracellular matrix ultrastructure. After culturing with TDP medium, the Young\u2019s modulus of the modeled KC corneas increased by ~50%, comparable to normal cornea controls. Similarly, the thermal denaturation temperature of the corneas was restored. These findings also corresponded to a significant increase in collagen fibril density after TDP treatment. Furthermore, corneas cultured in TDP medium significantly downregulated expression of the pro-inflammatory gene Tnf\u03b1, and restored the expression of the key keratocyte markers Aldh, keratocan, and biglycan. Conclusions: Tissue-derived biological particles reinforce mechanical and thermal properties of corneal tissue in an ex vivo model of KC. Through this study, we demonstrate and characterize the previously unexplored impact of tissue-derived biological scaffolds on corneal biomechanics, thermal stability, and gene expression, presenting a potential new therapy for ocular disease.<\/jats:p>","DOI":"10.3390\/bioengineering6040090","type":"journal-article","created":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T11:14:35Z","timestamp":1569582875000},"page":"90","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tissue-Derived Biological Particles Restore Cornea Properties in an Enzyme-Mediated Corneal Ectatic Model"],"prefix":"10.3390","volume":"6","author":[{"given":"Hongbo","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Sichuan University, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1992-4951","authenticated-orcid":false,"given":"Xiaokun","family":"Wang","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA"},{"name":"Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21231, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoumyo","family":"Majumdar","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA"},{"name":"Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21231, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeeyeon","family":"Sohn","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung-Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter","family":"Stark","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer H.","family":"Elisseeff","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA"},{"name":"Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21231, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00441-016-2372-3","article-title":"Proteins of the corneal stroma: Importance in visual function","volume":"364","author":"Xuan","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.jcrs.2014.04.013","article-title":"Biomechanics of corneal ectasia and biomechanical treatments","volume":"40","author":"Roberts","year":"2014","journal-title":"J. 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