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

Fiona C. Simpson; Christopher D. McTiernan; Mohammad Mirazul Islam; Oleksiy Buznyk; Philip N. Lewis; Keith M. Meek; Michel Haagdorens; Cindy Audiger; Sylvie Lesage; François Xavier Gueriot; Isabelle Brunette; Marie Claude Robert; David Olsen; Laura Koivusalo; Aneta Liszka; Per Fagerholm; Miguel Gonzalez-Andrades; May Griffith

doi:10.1038/s42003-021-02108-y

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

Fiona C. Simpson
, Christopher D. McTiernan
, Mohammad Mirazul Islam
, Oleksiy Buznyk
, Philip N. Lewis
, Keith M. Meek
, Michel Haagdorens
, Cindy Audiger
, Sylvie Lesage
, François Xavier Gueriot
, Isabelle Brunette
, Marie Claude Robert
, David Olsen
, Laura Koivusalo
, Aneta Liszka
, Per Fagerholm
, Miguel Gonzalez-Andrades
, May Griffith^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Scientific › peer-review

30 Citations (Scopus)

9 Downloads (Pure)

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.

Original language	English
Article number	608
Journal	Communications biology
Volume	4
DOIs	https://doi.org/10.1038/s42003-021-02108-y
Publication status	Published - May 2021
Publication type	A1 Journal article-refereed

Funding

The GLP mini-pig study (AB16-07) was funded by a DBT-Vinnova Indo-Swedish strategic cooperative grant DNR 2013-04645, and conducted by Adlego AB. Funding for dendritic cell studies, data analyses was from CIHR grant 391487 to M.G. and I.B., Fonds de recherche en ophtalmologie de l’Université de Montréal (FROUM) to M.G. and SL, and a Caroline Durand Foundation Research Chair for Cellular Therapy in the Eye to M.G. F.C.S. was supported by a doctoral studentship from the Natural Sciences and Engineering Research Council of Canada (NSERC). K.M.M. and P.L. are funded by Programme Grant MR/S037829/1 from the U.K. Medical Research Council. M.G-A. acknowledges funding from ISCIII (ICI19/00006), co-funded by ERDF/ESF, “A way to make Europe”/“Investing in your future”). M.G. holds the Tier 1 Canada Research Chair for Biomaterials and Stem Cells in Ophthalmology.

Publication forum classification

Publication forum level 1

ASJC Scopus subject areas

Medicine (miscellaneous)
General Biochemistry,Genetics and Molecular Biology
General Agricultural and Biological Sciences

Access to Document

10.1038/s42003-021-02108-yLicence: CC BY

s42003-021-02108-yFinal published version, 9.94 MBLicence: CC BY

http://urn.fi/URN:NBN:fi:tuni-202106185978Licence: CC BY

Cite this

Simpson, F. C., McTiernan, C. D., Islam, M. M., Buznyk, O., Lewis, P. N., Meek, K. M., Haagdorens, M., Audiger, C., Lesage, S., Gueriot, F. X., Brunette, I., Robert, M. C., Olsen, D., Koivusalo, L., Liszka, A., Fagerholm, P., Gonzalez-Andrades, M., & Griffith, M. (2021). Collagen analogs with phosphorylcholine are inflammation-suppressing scaffolds for corneal regeneration from alkali burns in mini-pigs. Communications biology, 4, Article 608. https://doi.org/10.1038/s42003-021-02108-y

@article{53bb209b5a9a4fd580ff5348bb1415e6,

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

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.",

author = "Simpson, \{Fiona C.\} and McTiernan, \{Christopher D.\} and Islam, \{Mohammad Mirazul\} and Oleksiy Buznyk and Lewis, \{Philip N.\} and Meek, \{Keith M.\} and Michel Haagdorens and Cindy Audiger and Sylvie Lesage and Gueriot, \{Fran{\c c}ois Xavier\} and Isabelle Brunette and Robert, \{Marie Claude\} and David Olsen and Laura Koivusalo and Aneta Liszka and Per Fagerholm and Miguel Gonzalez-Andrades and May Griffith",

note = "Funding Information: The GLP mini-pig study (AB16-07) was funded by a DBT-Vinnova Indo-Swedish strategic cooperative grant DNR 2013-04645, and conducted by Adlego AB. Funding for dendritic cell studies, data analyses was from CIHR grant 391487 to M.G. and I.B., Fonds de recherche en ophtalmologie de l{\textquoteright}Universit{\'e} de Montr{\'e}al (FROUM) to M.G. and SL, and a Caroline Durand Foundation Research Chair for Cellular Therapy in the Eye to M.G. F.C.S. was supported by a doctoral studentship from the Natural Sciences and Engineering Research Council of Canada (NSERC). K.M.M. and P.L. are funded by Programme Grant MR/S037829/1 from the U.K. Medical Research Council. M.G-A. acknowledges funding from ISCIII (ICI19/00006), co-funded by ERDF/ESF, “A way to make Europe”/“Investing in your future”). M.G. holds the Tier 1 Canada Research Chair for Biomaterials and Stem Cells in Ophthalmology. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = may,

doi = "10.1038/s42003-021-02108-y",

language = "English",

volume = "4",

}

Simpson, FC, McTiernan, CD, Islam, MM, Buznyk, O, Lewis, PN, Meek, KM, Haagdorens, M, Audiger, C, Lesage, S, Gueriot, FX, Brunette, I, Robert, MC, Olsen, D, Koivusalo, L, Liszka, A, Fagerholm, P, Gonzalez-Andrades, M & Griffith, M 2021, 'Collagen analogs with phosphorylcholine are inflammation-suppressing scaffolds for corneal regeneration from alkali burns in mini-pigs', Communications biology, vol. 4, 608. https://doi.org/10.1038/s42003-021-02108-y

TY - JOUR

T1 - Collagen analogs with phosphorylcholine are inflammation-suppressing scaffolds for corneal regeneration from alkali burns in mini-pigs

AU - Simpson, Fiona C.

AU - McTiernan, Christopher D.

AU - Islam, Mohammad Mirazul

AU - Buznyk, Oleksiy

AU - Lewis, Philip N.

AU - Meek, Keith M.

AU - Haagdorens, Michel

AU - Audiger, Cindy

AU - Lesage, Sylvie

AU - Gueriot, François Xavier

AU - Brunette, Isabelle

AU - Robert, Marie Claude

AU - Olsen, David

AU - Koivusalo, Laura

AU - Liszka, Aneta

AU - Fagerholm, Per

AU - Gonzalez-Andrades, Miguel

AU - Griffith, May

N1 - Funding Information: The GLP mini-pig study (AB16-07) was funded by a DBT-Vinnova Indo-Swedish strategic cooperative grant DNR 2013-04645, and conducted by Adlego AB. Funding for dendritic cell studies, data analyses was from CIHR grant 391487 to M.G. and I.B., Fonds de recherche en ophtalmologie de l’Université de Montréal (FROUM) to M.G. and SL, and a Caroline Durand Foundation Research Chair for Cellular Therapy in the Eye to M.G. F.C.S. was supported by a doctoral studentship from the Natural Sciences and Engineering Research Council of Canada (NSERC). K.M.M. and P.L. are funded by Programme Grant MR/S037829/1 from the U.K. Medical Research Council. M.G-A. acknowledges funding from ISCIII (ICI19/00006), co-funded by ERDF/ESF, “A way to make Europe”/“Investing in your future”). M.G. holds the Tier 1 Canada Research Chair for Biomaterials and Stem Cells in Ophthalmology. Publisher Copyright: © 2021, The Author(s).

PY - 2021/5

Y1 - 2021/5

N2 - 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.

AB - 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.

U2 - 10.1038/s42003-021-02108-y

DO - 10.1038/s42003-021-02108-y

M3 - Article

C2 - 34021240

AN - SCOPUS:85106596119

SN - 2399-3642

VL - 4

JO - Communications biology

JF - Communications biology

M1 - 608

ER -

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

Abstract

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