Collagen analogs with phosphorylcholine are inflammation-suppressing scaffolds for corneal regeneration from alkali burns in mini-pigs.
Fiona C SimpsonChristopher D McTiernanMohammad Mirazul IslamOleksiy BuznykPhilip N LewisKeith M MeekMichel HaagdorensCindy AudigerSylvie LesageFrançois-Xavier GueriotIsabelle BrunetteMarie-Claude RobertDavid OlsenLaura KoivusaloAneta LiszkaPer FagerholmMiguel Gonzalez-AndradesMay GriffithPublished in: Communications biology (2021)
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.
Keyphrases
- wound healing
- drug delivery
- oxidative stress
- soft tissue
- stem cells
- tissue engineering
- optical coherence tomography
- signaling pathway
- minimally invasive
- mesenchymal stem cells
- diabetic rats
- cataract surgery
- molecular docking
- acute coronary syndrome
- atrial fibrillation
- stress induced
- drug induced
- tandem mass spectrometry