RESEARCH PAPER Controlled Delivery of Fibroblast Growth Factor-9 from Biodegradable Poly(ester amide) Fibers for Building Functional Neovasculature Somiraa S. Said & J. Geoffrey Pickering & Kibret Mequanint Received: 5 March 2014 /Accepted: 12 May 2014 /Published online: 24 May 2014 # Springer Science+Business Media New York 2014 ABSTRACT Purpose 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 emul- sion 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 ex- pression in NIH-3T3 fibroblasts, 10T1/2 cells, and human coro- nary 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. Conclusion This study supports the premise of controlled deliv- ery of FGF9 from PEA electrospun fibers for potential therapeutic angiogenesis applications. KEY WORDS Electrospinning . Fibroblast growth factor-9 . Poly(ester amide)s . Therapeutic angiogenesis INTRODUCTION Ischemic vascular diseases are characterized by inadequate delivery of blood and oxygen to tissues; coronary artery dis- ease affects the heart, cerebrovascular disease affects the brain, and the peripheral arterial disease affects skeletal muscles and other internal organs (1). The principal pathological process causing ischemic diseases is atherosclerosis, which is a progressive inflammatory condition that usually affects large arteries, in which the accumulation of lipids, inflammatory cells, and fibrous material in the inner arterial wall results in the occlusion of these arteries (2). Many ischemic disease patients are ineligible for standard revascularization techniques due to poor overall health status or underlying comorbidities. Furthermore, a significant percentage of patients undergoing revascularization procedures do not meet the desired treatment outcome or experience restenosis, resulting in a poor prognosis and diminished quality of life, necessitating novel therapeutic alternatives for treatment of ischemic diseases (1). Therapeutic angiogenesis, which includes the administra- tion of growth factors for new and stable blood vessel forma- tion, is an appealing approach to simulate angiogenesis in order to improve tissue perfusion and accelerate tissue regen- eration in several pathological conditions such as ischemic heart disease, critical limb ischemia, diabetic ulcers, and de- layed wound healing, leading to the functional recovery of ischemic tissues. However, the short half-life of exogenously delivered growth factors results in their rapid clearance from S. S. Said Biomedical Engineering Graduate Program The University of Western Ontario, London, Ontario, Canada J. G. Pickering Department of Medicine (Cardiology), Department of Biochemistry, and Department of Medical Biophysics The University of Western Ontario, London, Ontario, Canada K. Mequanint (*) Department of Chemical and Biochemical Engineering and Biomedical Engineering Graduate Program, The University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 5B9, Canada e-mail: kmequani@uwo.ca Pharm Res (2014) 31:3335–3347 DOI 10.1007/s11095-014-1423-2