title: Heparin-modified dendrimer cross-linked collagen matrices for the delivery of basic fibroblast growth factor (FGF-2).
abstract: Tissue integration between a tissue-engineered corneal equivalent and the host eye is of critical importance in ensuring long-term implant success. A novel dendrimer cross-linked collagen scaffold has previously shown good corneal epithelial cell compatibility in vitro particularly when the highly functional dendrimer cross-linkers were functionalized to introduce additional biological groups. Herein we investigated heparinization of these materials and their potential to facilitate the delivery of basic fibroblast growth factor (FGF-2) in an active form, ultimately for use as a corneal tissue scaffold. Collagen gels cross-linked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) chemistry, and varying amounts of polypropyleneimine octaamine generation 2 (G2) dendimer and heparin were synthesized. Swelling studies and differential scanning calorimetry characterization indicated higher gel stability with the introduction of dendrimer cross-linking, which was not compromised by heparin integration. Dendrimer cross-linked gels with or without heparin gave multiple denaturation peaks, as did the heparinized EDC gels. This is thought to be the result of the heterogeneous cross-linking possible between collagen, the dendrimer and heparin. Release of FGF-2 from collagen gels showed typical first-order kinetics, with an initial burst followed by a prolonged gradual release. Heparinized dendrimer cross-linked gels released approx. 40% of the growth factor over a 2-week period, with significance maintenance of growth factor activity. Incorporation of heparin resulted in somewhat prolonged release from these systems.
authors: Department of Chemical Engineering, McMaster University, Hamilton, ON, Canada.
authors: M A
authors: MA
authors: Princz
authors: H
authors: H
authors: Sheardown
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D003094:Collagen / Q000737:chemistry* / Q000378:metabolism; D003315:Cornea / Q000166:cytology; D003432:Cross-Linking Reagents / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D005782:Gels / Q000737:chemistry* / Q000378:metabolism; D006493:Heparin / Q000737:chemistry / Q000378:metabolism*; D008422:Materials Testing; D015394:Molecular Structure; D011489:Protein Denaturation; D017154:Stromal Cells / Q000166:cytology; D023822:Tissue Engineering
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D050091:Dendrimers; D004337:Drug Carriers; D005782:Gels; D016222:Fibroblast Growth Factor 2; D006493:Heparin; D003094:Collagen