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

Autor: Monika Kozak Ljunggren, Michel Haagdorens, Mohammad Mirazul Islam, Jaganmohan Reddy Jangamreddy, May Griffith, Nadia Zakaria, Philip N. Lewis, Ayan Samanta, Per Fagerholm, Emilio I. Alarcon, Keith M. Meek, Oleksiy Buznyk, Aneta Liszka
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Swine
Biomaterialvetenskap
Biomedical Engineering
Peptide
02 engineering and technology
Exosomes
Biochemistry
Article
Polyethylene Glycols
Cornea
Biomaterials
03 medical and health sciences
Implants
Experimental
Tissue engineering
Collagen-like peptide
medicine
Animals
Humans
Regeneration
Recombinant human collagen
Molecular Biology
ComputingMethodologies_COMPUTERGRAPHICS
Cell Line
Transformed
chemistry.chemical_classification
Physics
Regeneration (biology)
Biochemistry and Molecular Biology
General Medicine
Extracellular vesicle
021001 nanoscience & nanotechnology
In vitro
3. Good health
Cell biology
030104 developmental biology
medicine.anatomical_structure
chemistry
Mechanism of action
Self-healing hydrogels
Biomaterials Science
Swine
Miniature
Collagen
medicine.symptom
Peptides
0210 nano-technology
Biokemi och molekylärbiologi
Biotechnology
Zdroj: Acta biomaterialia
Acta Biomaterialia
ISSN: 1742-7061
Popis: Graphical 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.
Databáze: OpenAIRE
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