Controlled delivery of fibroblast growth factor-9 from biodegradable poly(ester amide) fibers for building functional neovasculature.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
This study supports the premise of controlled delivery of FGF9 from PEA electrospun fibers for potential therapeutic angiogenesis applications.
Biomedical Engineering Graduate Program, The University of Western Ontario, London, Ontario, Canada.
Somiraa S
SS
Said
J Geoffrey
JG
Pickering
Kibret
K
Mequanint
D000577:Amides; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects; D003692:Delayed-Action Preparations; D051525:Fibroblast Growth Factor 9 / Q000008:administration & dosage* / Q000494:pharmacology*; D051379:Mice; D018613:Microscopy, Confocal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D041681:NIH 3T3 Cells; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011091:Polyesters
D000577:Amides; D003692:Delayed-Action Preparations; D051525:Fibroblast Growth Factor 9; D011091:Polyesters