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Epoxy Cross-Linked Collagen and Collagen-Laminin Peptide Hydrogels as Corneal Substitutes
Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics. Linköping University, The Institute of Technology.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Swedish Nanoscience Center, Karolinska Institute, Stockholm , Sweden .
Ottawa Hospital Research Institute, University of Ottawa Eye Institute, ON, Canada.
Ottawa Hospital Research Institute, University of Ottawa Eye Institute, ON, Canada.
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2013 (English)In: Journal of Functional Biomaterials, ISSN 2079-4983, Vol. 4, no 3, 162-177 p.Article in journal (Refereed) Published
Abstract [en]

A bi-functional epoxy-based cross-linker, 1,4-Butanediol diglycidyl ether (BDDGE), was investigated in the fabrication of collagen based corneal substitutes. Two synthetic strategies were explored in the preparation of the cross-linked collagen scaffolds. The lysine residues of Type 1 porcine collagen were directly cross-linked using l,4-Butanediol diglycidyl ether (BDDGE) under basic conditions at pH 11. Alternatively, under conventional methodology, using both BDDGE and 1-Ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) as cross-linkers, hydrogels were fabricated under acidic conditions. In this latter strategy, Cu(BF4)2·XH2O was used to catalyze the formation of secondary amine bonds. To date, we have demonstrated that both methods of chemical cross-linking improved the elasticity and tensile strength of the collagen implants. Differential scanning calorimetry and biocompatibility studies indicate comparable, and in some cases, enhanced properties compared to that of the EDC/NHS controls. In vitro studies showed that human corneal epithelial cells and neuronal progenitor cell lines proliferated on these hydrogels. In addition, improvement of cell proliferation on the surfaces of the materials was observed when neurite promoting laminin epitope, IKVAV, and adhesion peptide, YIGSR, were incorporated. However, the elasticity decreased with peptide incorporation and will require further optimization. Nevertheless, we have shown that epoxy cross-linkers should be further explored in the fabrication of collagen-based hydrogels, as alternatives to or in conjunction with carbodiimide cross-linkers.

Place, publisher, year, edition, pages
Basel, Switzerland: MDPI AG , 2013. Vol. 4, no 3, 162-177 p.
Keyword [en]
biomimetic materials; cross-linking; collagen; cornea; tissue engineering
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-98700DOI: 10.3390/jfb4030162OAI: diva2:655434
Available from: 2013-10-11 Created: 2013-10-11 Last updated: 2014-04-17Bibliographically approved

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Koh, Li BuayIslam, Mohammad MirazulFagerholm, PerLiedberg, BoPhopase, JaywantGriffith, May
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Sensor Science and Molecular PhysicsThe Institute of TechnologyDivision of Cell BiologyFaculty of Health SciencesDivision of NeuroscienceDepartment of Ophthalmology in Linköping
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