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Open AccessArticle

Tissue-Derived Biological Particles Restore Cornea Properties in an Enzyme-Mediated Corneal Ectatic Model

1
Department of Ophthalmology, Sichuan University, Chengdu 610041, China
2
Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA
3
Translational Tissue Engineering Center, Wilmer Eye Institute and the Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21231, USA
4
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally in this study.
Bioengineering 2019, 6(4), 90; https://doi.org/10.3390/bioengineering6040090
Received: 24 July 2019 / Revised: 18 September 2019 / Accepted: 24 September 2019 / Published: 27 September 2019
(This article belongs to the Special Issue Extracellular Matrix in Wound Healing)
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’s 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 Tnfα, 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. View Full-Text
Keywords: extracellular matrix; corneal mechanics; keratoconus; collagen crosslinking extracellular matrix; corneal mechanics; keratoconus; collagen crosslinking
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MDPI and ACS Style

Yin, H.; Wang, X.; Majumdar, S.; Sohn, J.; Kim, B.-J.; Stark, W.; Elisseeff, J.H. Tissue-Derived Biological Particles Restore Cornea Properties in an Enzyme-Mediated Corneal Ectatic Model. Bioengineering 2019, 6, 90. https://doi.org/10.3390/bioengineering6040090

AMA Style

Yin H, Wang X, Majumdar S, Sohn J, Kim B-J, Stark W, Elisseeff JH. Tissue-Derived Biological Particles Restore Cornea Properties in an Enzyme-Mediated Corneal Ectatic Model. Bioengineering. 2019; 6(4):90. https://doi.org/10.3390/bioengineering6040090

Chicago/Turabian Style

Yin, Hongbo; Wang, Xiaokun; Majumdar, Shoumyo; Sohn, Jeeyeon; Kim, Byung-Jin; Stark, Walter; Elisseeff, Jennifer H. 2019. "Tissue-Derived Biological Particles Restore Cornea Properties in an Enzyme-Mediated Corneal Ectatic Model" Bioengineering 6, no. 4: 90. https://doi.org/10.3390/bioengineering6040090

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