Epoxy Cross-Linked Collagen and Collagen-Laminin Peptide Hydrogels as Corneal Substitutes

Journal of Functional Biomaterials

Li Buay Koh²  Mohammad Mirazul Islam⁵  Debbie Mitra³  Christopher W. Noel³  Kimberley Merrett⁴  Silvia Odorcic³  Per Fagerholm⁴  William. Bruce Jackson³  Bo Liedberg¹  Jaywant Phopase² 

[1] Center for Biomimetic Sensor Science, Nanyang Technological University, Singapore; E-Mail:;Integrative Regenerative Medicine Center, Department of Physics, Chemistry and Biology, Linköping University, SE 581 83 Linköping, Sweden; E-Mails:;Ottawa Hospital Research Institute, University of Ottawa Eye Institute, 501 Smyth Rd. Ottawa, ON K1H 8L6, Canada; E-Mails:;Integrative Regenerative Medicine Center & Department of Clinical and Experimental Medicine, Cell Biology Building, Linköping University, SE 581 85 Linköping, Sweden; E-Mails:;Swedish Nanoscience Center, Karolinska Institute, 171 77 Stockholm , Sweden; E-Mail:

关键词: biomimetic materials;    cross-linking;    collagen;    cornea;    tissue engineering;   

DOI  :  10.3390/jfb4030162

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.