title: Epoxy cross-linked collagen and collagen-laminin Peptide hydrogels as corneal substitutes.
abstract: 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.
authors: Integrative Regenerative Medicine Center, Department of Physics, Chemistry and Biology, Linköping University, SE 581 83 Linköping, Sweden. mayko@ifm.liu.se.
authors: Li Buay
authors: LB
authors: Koh
authors: Swedish Nanoscience Center, Karolinska Institute, 171 77 Stockholm , Sweden. mohammad.islam@ki.se.
authors: Mohammad Mirazul
authors: MM
authors: Islam
authors: Ottawa Hospital Research Institute, University of Ottawa Eye Institute, 501 Smyth Rd. Ottawa, ON K1H 8L6, Canada. debbiemitra@hotmail.com.
authors: Debbie
authors: D
authors: Mitra
authors: Ottawa Hospital Research Institute, University of Ottawa Eye Institute, 501 Smyth Rd. Ottawa, ON K1H 8L6, Canada. christophernoel90@gmail.com.
authors: Christopher W
authors: CW
authors: Noel
authors: Integrative Regenerative Medicine Center & Department of Clinical and Experimental Medicine, Cell Biology Building, Linköping University, SE 581 85 Linköping, Sweden. kim.merrett@sympatico.ca.
authors: Kimberley
authors: K
authors: Merrett
authors: Ottawa Hospital Research Institute, University of Ottawa Eye Institute, 501 Smyth Rd. Ottawa, ON K1H 8L6, Canada. silvia.odorcic@gmail.com.
authors: Silvia
authors: S
authors: Odorcic
authors: Integrative Regenerative Medicine Center & Department of Clinical and Experimental Medicine, Cell Biology Building, Linköping University, SE 581 85 Linköping, Sweden. per.fagerholm@liu.se.
authors: Per
authors: P
authors: Fagerholm
authors: Ottawa Hospital Research Institute, University of Ottawa Eye Institute, 501 Smyth Rd. Ottawa, ON K1H 8L6, Canada. bjackson@ohri.ca.
authors: William Bruce
authors: WB
authors: Jackson
authors: Center for Biomimetic Sensor Science, Nanyang Technological University, Singapore. bliedberg@ntu.edu.sg.
authors: Bo
authors: B
authors: Liedberg
authors: Integrative Regenerative Medicine Center, Department of Physics, Chemistry and Biology, Linköping University, SE 581 83 Linköping, Sweden. jayph@ifm.liu.se.
authors: Jaywant
authors: J
authors: Phopase
authors: Swedish Nanoscience Center, Karolinska Institute, 171 77 Stockholm , Sweden. may.griffith@liu.se.
authors: May
authors: M
authors: Griffith