4.7 Article

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

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COMMUNICATIONS BIOLOGY
卷 4, 期 1, 页码 -

出版社

NATURE RESEARCH
DOI: 10.1038/s42003-021-02108-y

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资金

  1. DBT-Vinnova Indo-Swedish strategic cooperative grant [AB16-07, DNR 2013-04645]
  2. CIHR [391487]
  3. Fonds de recherche en ophtalmologie de l'Universite de Montreal (FROUM)
  4. Caroline Durand Foundation Research Chair for Cellular Therapy in the Eye
  5. Natural Sciences and Engineering Research Council of Canada (NSERC)
  6. U.K. Medical Research Council [MR/S037829/1]
  7. ISCIII [ICI19/00006]
  8. ERDF/ESF
  9. DBT-Vinnova Indo-Swedish grant

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By developing fully synthetic corneal implants, Simpson, McTiernan et al. demonstrate that CLP-PEG-MPC implants show reduced inflammation-induced corneal rejection, promote faster nerve regeneration and recovery of corneal sensation compared to CLP-PEG only implants. The study suggests the superiority of CLP-PEG-MPC implants in promoting corneal regeneration.
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. Simpson, McTiernan et al. develop fully synthetic corneal implants. The resulting CLP-PEG-MPC implants show reduced corneal swelling, haze, and neovascularization compared to CLP-PEG only implants when grafted into a mini-pig cornea alkali burn model of inflammation over 12 months. This study suggests the superiority of CLP-PEG-MPC implants over the CLP-PEG only implants.

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