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Collagen analogs with phosphorylcholine are inflammation-suppressing scaffolds for corneal regeneration from alkali burns in mini-pigs

Simpson, Fiona C., McTiernan, Christopher D., Islam, Mohammad Mirazul, Buznyk, Oleksiy, Lewis, Philip N., Meek, Keith M., Haagdorens, Michel, Audiger, Cindy, Lesage, Sylvie, Gueriot, François-Xavier, Brunette, Isabelle, Robert, Marie-Claude, Olsen, David, Koivusalo, Laura, Liszka, Aneta, Fagerholm, Per, Gonzalez-Andrades, Miguel and Griffith, May 2021. Collagen analogs with phosphorylcholine are inflammation-suppressing scaffolds for corneal regeneration from alkali burns in mini-pigs. Communications Biology 4 (1) , 608. 10.1038/s42003-021-02108-y

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Abstract

The long-term survival of biomaterial implants is often hampered by surgery-induced inflammation that can lead to graft failure. Considering that most corneas receiving grafts are either pathological or inflamed before implantation, the risk of rejection is heightened. Here, we show that bioengineered, fully synthetic, and robust corneal implants can be manufactured from a collagen analog (collagen-like peptide-polyethylene glycol hybrid, CLP-PEG) and inflammation-suppressing polymeric 2-methacryloyloxyethyl phosphorylcholine (MPC) when stabilized with the triazine-based crosslinker 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. The resulting CLP-PEG-MPC implants led to reduced corneal swelling, haze, and neovascularization in comparison to CLP-PEG only implants when grafted into a mini-pig cornea alkali burn model of inflammation over 12 months. Implants incorporating MPC allowed for faster nerve regeneration and recovery of corneal sensation. CLP-PEG-MPC implants appear to be at a more advanced stage of regeneration than the CLP-PEG only implants, as evidenced by the presence of higher amounts of cornea-specific type V collagen, and a corresponding decrease in the presence of extracellular vesicles and exosomes in the corneal stroma, in keeping with the amounts present in healthy, unoperated corneas.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Optometry and Vision Sciences
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher: Nature Research
ISSN: 2399-3642
Date of First Compliant Deposit: 27 May 2021
Date of Acceptance: 16 March 2021
Last Modified: 27 May 2021 09:15
URI: http://orca.cardiff.ac.uk/id/eprint/141570

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