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Crosslinked collagen hydrogels as corneal implants: Effects of sterically bulky vs. non-bulky carbodiimides as crosslinkers
Ottawa Hospital, Canada .
University of Aberdeen, Scotland .
Ottawa Hospital, Canada .
Ottawa Hospital, Canada .
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2013 (English)In: Acta Biomaterialia, ISSN 1742-7061, Vol. 9, no 8, 7796-7805 p.Article in journal (Refereed) Published
Abstract [en]

We have previously shown that recombinant human collagen can be crosslinked with N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDC) to fabricate transparent hydrogels possessing the shape and dimensions of the human cornea. These corneal implants have been tested in a Phase I human clinical study. Although these hydrogels successfully promoted corneal tissue and nerve regeneration, the gelling kinetics were difficult to control during the manufacture of the implants. An alternative carbodiimide capable of producing hydrogels of similar characteristics as EDC in terms of strength and biocompatibility, but with a longer gelation time would be a desirable alternative. Here, we compared the crosslinking kinetics and properties of hydrogels crosslinked with a sterically bulky carbodiimide, N-Cyclohexyl-N-(2-morpholinoethyl) carbodiimide metho-p-toluenesulfonate (CMC), with that of EDC. CMC crosslinking was possible at ambient temperature whereas the EDC reaction was too rapid to control and had to be carried out at low temperatures. The highest tensile strength obtained using optimized formulations were equivalent, although CMC crosslinked hydrogels were found to be stiffer. The collagenase resistance of CMC crosslinked hydrogels was superior to that of EDC crosslinked hydrogels while biocompatibility was similar. We are also able to substitute porcine collagen with recombinant human collagen and show that the in vivo performance of both resulting hydrogels as full-thickness corneal implants is comparable in a mouse model of an orthotopic corneal graft. In conclusion, CMC is a viable alternative to EDC as a crosslinker for collagen-based biomaterials for use as corneal implants, and potentially for use in other tissue engineering applications.

Place, publisher, year, edition, pages
Elsevier , 2013. Vol. 9, no 8, 7796-7805 p.
Keyword [en]
Collagen, Crosslinking, Carbodiimides, Cornea, Orthotropic corneal graft
National Category
Social Sciences
URN: urn:nbn:se:liu:diva-96701DOI: 10.1016/j.actbio.2013.04.014ISI: 000322207700020OAI: diva2:642980

Funding Agencies|CIHR Canada Emerging Team Grant for Regenerative Medicine and Nanomedicine||Canadian DFAIT||Linkoping University Integrative Regenerative Medicine (IGEN) Centre, Linkoping, Sweden||Development Trust of University of Aberdeen||NHS Grampian Endowment|12/49|

Available from: 2013-08-23 Created: 2013-08-23 Last updated: 2013-12-17

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Griffith, May
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Division of Cell BiologyFaculty of Health Sciences
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