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Acta Biomater. 2018 Mar 15;69:120-130. doi: 10.1016/j.actbio.2018.01.011. Epub 2018 Jan 31.

Short peptide analogs as alternatives to collagen in pro-regenerative corneal implants.

Author information

1
Dept. of Clinical and Experimental Medicine, Linköping University, S-58185 Linköping, Sweden; Tej Kohli Cornea Institute, LV Prasad Eye Institute, Hyderabad - 500 034, India.
2
Dept. of Ophthalmology, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Antwerp, Belgium; Faculty of Medicine and Health Sciences, Department of Ophthalmology, Visual Optics and Visual Rehabilitation, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Antwerp, Belgium.
3
Dept. of Clinical and Experimental Medicine, Linköping University, S-58185 Linköping, Sweden.
4
Structural Biophysics Group, School of Optometry and Vision Sciences, Cardiff University, Wales CF24 4HQ, UK.
5
Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y 4W7, Canada.
6
Dept. of Ophthalmology, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Antwerp, Belgium; Faculty of Medicine and Health Sciences, Department of Ophthalmology, Visual Optics and Visual Rehabilitation, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Antwerp, Belgium. Electronic address: nadia.zakaria@uantwerpen.be.
7
Structural Biophysics Group, School of Optometry and Vision Sciences, Cardiff University, Wales CF24 4HQ, UK. Electronic address: MeekKM@cardiff.ac.uk.
8
Dept. of Clinical and Experimental Medicine, Linköping University, S-58185 Linköping, Sweden; Maisonneuve-Rosemont Hospital Research Centre and Dept. of Ophthalmology, University of Montreal, Montreal, QC H1T 4B3, Canada. Electronic address: May.Griffith@umontreal.ca.

Abstract

Short collagen-like peptides (CLPs) are being proposed as alternatives to full-length collagen for use in tissue engineering, on their own as soft hydrogels, or conjugated to synthetic polymer for mechanical strength. However, despite intended clinical use, little is known about their safety and efficacy, mechanism of action or degree of similarity to the full-length counterparts they mimic. Here, we show the functional equivalence of a CLP conjugated to polyethylene glycol (CLP-PEG) to full-length recombinant human collagen in vitro and in promoting stable regeneration of corneal tissue and nerves in a pre-clinical mini-pig model. We also show that these peptide analogs exerted their pro-regeneration effects through stimulating extracellular vesicle production by host cells. Our results support future use of CLP-PEG implants for corneal regeneration, suggesting the feasibility of these or similar peptide analogs in clinical application in the eye and other tissues.

STATEMENT OF SIGNIFICANCE:

Although biomaterials comprising full-length recombinant human collagen and extracted animal collagen have been evaluated and used clinically, these macromolecules provide only a limited number of functional groups amenable to chemical modification or crosslinking and are demanding to process. Synthetic, customizable analogs that are functionally equivalent, and can be readily scaled-up are therefore very desirable for pre-clinical to clinical translation. Here, we demonstrate, using cornea regeneration as our test bed, that collagen-like-peptides conjugated to multifunctional polyethylene glycol (CLP-PEG) when grafted into mini-pigs as corneal implants were functionally equivalent to recombinant human collagen-based implants that were successfully tested in patients. We also show for the first time that these materials affected regeneration through stimulation of extracellular vesicle production by endogenous host cells that have migrated into the CLP-PEG scaffolds.

KEYWORDS:

Collagen-like peptide; Cornea; Exosomes; Recombinant human collagen; Regeneration

PMID:
29355715
PMCID:
PMC5842042
DOI:
10.1016/j.actbio.2018.01.011
[Indexed for MEDLINE]
Free PMC Article

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