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Tethering of Epidermal Growth Factor Family Members to Dendrimer Crosslinked Collagen Gels

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To enhance growth factor (GF) bioavailability, epidermal growth factor (EGF) and heparin-binding epidermal growth factor (HB-EGF) were tethered, via carbodiimide chemistry, to dendrimer crosslinked collagen (CG) gels, either during or following gel fabrication. GF tethering was achieved either via step-wise modification, with gels soaked in activated GF solutions, or via bulk modification with various GF solutions added to the collagen suspension prior to full dendrimer crosslinking of CG gels. Conjugation of EGF and HB-EGF to CG gels was tunable in relation to the original concentration of activated GF exposed to gels. Slightly higher amounts of tethered EGF, compared to HB-EGF, were initially obtained following step-wise conjugation, but differences were not evident following extensive rinsing, indicating the presence of both sorbed and tethered protein. Final tethered GF amounts were found to be dependent on solution concentration. As with step-wise modification, bulk modification of CG gels resulted in GF retention that could be tailored by adjusting the amount of GF added to the collagen suspension during gel fabrication. However, the various GF solutions utilized for CG bulk modification did not differ in terms of GF incorporation, following extensive rinsing, and represented between 2–5% of the originally added GF amount. Bioactivity of EGF and HB-EGF was enhanced following step-wise conjugation to gels, as was verified with proliferation of human corneal epithelial cells (HCEC); however, bulk modification of CG gels, with tethered GF, only maintained HCEC proliferation, suggesting step-wise conjugation is a favourable method for HB-EGF and EGF tethering to CG gels.
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Keywords: COLLAGEN; CORNEAL EPITHELIUM; DENDRIMERS; EPIDERMAL GROWTH FACTOR (EGF); HEPARIN-BINDING EPIDERMAL GROWTH FACTOR (HB-EGF); TISSUE ENGINEERED CORNEAL EQUIVALENTS (TECE)

Document Type: Research Article

Publication date: 2014-11-01

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  • Journal of Biomaterials and Tissue Engineering (JBT) is an international peer-reviewed journal that covers all aspects of biomaterials, tissue engineering and regenerative medicine. The journal focuses on the broad spectrum of research topics including all types of biomaterials, their properties, bioimplants and medical devices, biofilms, bioimaging, BioMEMS/NEMS, biosensors, fibers, tissue scaffolds, tissue engineering and modeling, artificial organs, tissue interfaces, interactions between biomaterials, blood, cells, tissues, and organs, regenerative medicine and clinical performance.
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