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Crosslinked collagen hydrogels as corneal implants: effects of sterically bulky vs. non-bulky carbodiimides as crosslinkers.

Abstract：

: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.

journal_name

Acta Biomater

journal_title

Acta biomaterialia

authors

Ahn JI,Kuffova L,Merrett K,Mitra D,Forrester JV,Li F,Griffith M

doi

10.1016/j.actbio.2013.04.014

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

7796-805

issue

eissn

1742-7061

issn

1878-7568

pii

S1742-7061(13)00186-4

journal_volume

pub_type

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Crosslinked collagen hydrogels as corneal implants: effects of sterically bulky vs. non-bulky carbodiimides as crosslinkers.