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Short peptide analogs as alternatives to collagen in pro-regenerative corneal implants
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. LV Prasad Eye Inst, India.ORCID iD: 0000-0001-6105-1213
Antwerp Univ Hosp, Belgium; Univ Antwerp, Belgium.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Cardiff Univ, Wales.
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2018 (English)In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 69, p. 120-130Article in journal (Refereed) Published
Abstract [en]

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- clinicalmini-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. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD , 2018. Vol. 69, p. 120-130
Keywords [en]
Collagen-like peptide; Recombinant human collagen; Cornea; Regeneration; Exosomes
National Category
Biomaterials Science
Identifiers
URN: urn:nbn:se:liu:diva-147108DOI: 10.1016/j.actbio.2018.01.011ISI: 000427334100009PubMedID: 29355715OAI: oai:DiVA.org:liu-147108DiVA, id: diva2:1199540
Note

Funding Agencies|Dept. of Biotechnology-Vinnova Indo-Sweden Collaborative Health Research Project grant; Integrative Regenerative Medicine Centre, Linkoping University; European Cooperation in Science and Technology (EU-COST) [BM1302-25221, BM1302-34283]; Research Foundation - Flanders [FWO - 11ZB315N]; Euronanomed2 (REGENERATE); Funds for Research in Ophthalmology (FRO); MRC program [MR/K000837/1]

Available from: 2018-04-20 Created: 2018-04-20 Last updated: 2019-03-22

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Jangamreddy, JaganmohanMirazul Islam, Mohammad MirazulSamanta, AyanFagerholm, PerLiszka, AnetaKozak Ljunggren, MonikaBuznyk, OleksiyGriffith, May
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Division of Cell BiologyFaculty of Medicine and Health SciencesDivision of Neuro and Inflammation ScienceDepartment of Ophthalmology in Linköping
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