Controlled Delivery of Fibroblast Growth Factor-9 from Biodegradable Poly(ester amide) Fibers for Building Functional Neovasculature
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For building functional vasculature, controlled delivery of fibroblast growth factor-9 (FGF9) from electrospun fibers is an appealing strategy to overcome challenges associated with its short half-life. FGF9 sustained delivery could potentially drive muscularization of angiogenic sprouts and help regenerate stable functional neovasculature in ischemic vascular disease patients.
Electrospinning parameters of FGF9-loaded poly(ester amide) (PEA) fibers have been optimized, using blend and emulsion electrospinning techniques. In vitro PEA matrix degradation, biocompatibility, FGF9 release kinetics, and bioactivity of the released FGF9 were evaluated. qPCR was employed to evaluate platelet-derived growth factor receptor-β (PDGFRβ) gene expression in NIH-3T3 fibroblasts, 10T1/2 cells, and human coronary artery smooth muscle cells cultured on PEA fibers at different FGF9 concentrations.
Loaded PEA fibers exhibited controlled release of FGF9 over 28 days with limited burst effect while preserving FGF9 bioactivity. FGF9-loaded and unloaded electrospun fibers were found to support the proliferation of fibroblasts for five days even in serum-depleted conditions. Cells cultured on FGF9-supplemented PEA mats resulted in upregulation of PDGFRβ in concentration and cell type-dependent manner.
This study supports the premise of controlled delivery of FGF9 from PEA electrospun fibers for potential therapeutic angiogenesis applications.
Key WordsElectrospinning Fibroblast growth factor-9 Poly(ester amide)s Therapeutic angiogenesis
Acknowledgments and Disclosures
The Authors acknowledge the financial support from The Heart and Stroke Foundation of Canada (T-7262), the Natural Sciences and Engineering Research Council of Canada, the Canadian Institutes for Health Research (FRN 11715), and the Canadian Cancer Society (Grant #701080). S. S. Said held a CIHR Strategic Training Fellowship in Vascular Research (2011–2013). J. G. Pickering holds the Heart and Stroke Foundation of Ontario/Barnett-Ivey Chair. Thanks to D. K. Knight for his assistance in the synthesis of PEA and performing the GPC molecular weight analysis.
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