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M. A. Princz, H. Sheardown; Release of Growth Factors from and in vitro Characterization of Dendrimer Crosslinked Heparinized Collagen Gels in Artificial Cornea Applications. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1870.
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The success of an artificial corneal device is greatly influenced by host tissue integration. Proper integration of the device with host tissue can be manipulated by cytokine incorporation. Here, we investigate the in vitro response of corneal cells to dendrimer crosslinked heparinized collagen gels, capable of delivering basic fibroblast growth factor (FGF-2) in a soluble form.
Novel dendrimer crosslinked collagen gels with covalently incorporated heparin were prepared, with varying concentrations of heparin to optimize device clarity and FGF-2 immobilization. The release of FGF-2 was measured under physiologically relevant, wound-healing conditions and the amount of released FGF-2 required to stimulate stromal cells and cornea epithelial cells in vitro was determined. Cell phenotype was monitored through cell morphology, and cellular markers, while cell viability, cell proliferation and cell migration were also assessed. Extracellular matrix production and cell adhesion were investigated with immunofluorescence, as was adhesion under shear. Furthermore, the influence of FGF-2 on the cells was determined through FGF-2 and other growth factor gene expression and secretion, and FGF-2 receptor regulation.
Heparin has been incorporated into collagen gels, both physically and chemically through crosslinking with dendrimers, and optimized to improve gel transparency and integrity. Heparin availability was found to influence FGF-2 immobilization, which may allow for tailoring to achieve the desired wound healing response. FGF-2 release from gels demonstrated a gradual first order release profile. Preliminary in vitro tests demonstrate that these concentrations are suitable for stimulating corneal epithelial and stromal cells.
Dendrimer crosslinked collagen gels were fabricated with immobilized heparin and are capable of slowly delivery FGF-2. These materials are able to act as delivery vehicles for soluble growth factors and have potential for improving native host integration with an artificial cornea.
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