2. Academic Validation
  3. Collagen analogs with phosphorylcholine are inflammation-suppressing scaffolds for corneal regeneration from alkali burns in mini-pigs

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

  • Commun Biol. 2021 May 21;4(1):608. doi: 10.1038/s42003-021-02108-y.
Fiona C Simpson # 1 2 3 4,  Christopher D McTiernan # 5,  Mohammad Mirazul Islam 6,  Oleksiy Buznyk 7 8,  Philip N Lewis 9,  Keith M Meek 9,  Michel Haagdorens 10,  Cindy Audiger 1 11,  Sylvie Lesage 1 11,  François-Xavier Gueriot 1 12,  Isabelle Brunette 1 2,  Marie-Claude Robert 1 4,  David Olsen 13,  Laura Koivusalo 14,  Aneta Liszka 7,  Per Fagerholm 15,  Miguel Gonzalez-Andrades 16 17,  May Griffith 18 19 20 21
Affiliations

Affiliations

  • 1 Centre de recherche, Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada.
  • 2 Départment d'Ophtalmologie, Université de Montréal, Montréal, QC, Canada.
  • 3 Institut du Génie Biomédicale, Université de Montréal, Montréal, QC, Canada.
  • 4 Centre de recherche du Centre hospitalier de l'Université de Montréal, Montréal, QC, Canada.
  • 5 Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, ON, Canada.
  • 6 Disruptive Technology Laboratory, Massachusetts Eye and Ear and Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
  • 7 Institute for Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
  • 8 Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine, Odessa, Ukraine.
  • 9 School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK.
  • 10 Department of Ophthalmology, Visual Optics and Visual Rehabilitation, University of Antwerp, Antwerp, Belgium.
  • 11 Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, QC, Canada.
  • 12 Department of Ophthalmology, Valence Hospital, Valence, France.
  • 13 FibroGen Inc., San Francisco, CA, USA.
  • 14 Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
  • 15 Institute for Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. Per.Fagerholm@liu.se.
  • 16 Disruptive Technology Laboratory, Massachusetts Eye and Ear and Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA. miguel.gonzalez@imibic.org.
  • 17 Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Department of Ophthalmology, Reina Sofia University Hospital and University of Cordoba, Cordoba, Spain. miguel.gonzalez@imibic.org.
  • 18 Centre de recherche, Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada. May.Griffith@umontreal.ca.
  • 19 Départment d'Ophtalmologie, Université de Montréal, Montréal, QC, Canada. May.Griffith@umontreal.ca.
  • 20 Institut du Génie Biomédicale, Université de Montréal, Montréal, QC, Canada. May.Griffith@umontreal.ca.
  • 21 Centre de recherche du Centre hospitalier de l'Université de Montréal, Montréal, QC, Canada. May.Griffith@umontreal.ca.
  • # Contributed equally.
PMID: 34021240 DOI: 10.1038/s42003-021-02108-y
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.

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