Said Somiraa S, Pickering J Geoffrey, Mequanint Kibret
Biomedical Engineering Graduate Program, The University of Western Ontario, London, Ontario, Canada.
Pharm Res. 2014 Dec;31(12):3335-47. doi: 10.1007/s11095-014-1423-2. Epub 2014 May 24.
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.
为构建功能性脉管系统，通过电纺纤维可控释放成纤维细胞生长因子9（FGF9）是一种有吸引力的策略，可克服与其短半衰期相关的挑战。FGF9的持续释放可能会驱动血管生成芽的肌化，并有助于缺血性血管疾病患者再生稳定的功能性新生血管。
采用共混和乳液电纺技术，优化了负载FGF9的聚（酯酰胺）（PEA）纤维的电纺参数。评估了体外PEA基质降解、生物相容性、FGF9释放动力学以及释放的FGF9的生物活性。采用qPCR评估在不同FGF9浓度的PEA纤维上培养的NIH-3T3成纤维细胞、10T1/2细胞和人冠状动脉平滑肌细胞中血小板衍生生长因子受体-β（PDGFRβ）基因的表达。
负载的PEA纤维在28天内实现了FGF9的可控释放，突发效应有限，同时保留了FGF9的生物活性。发现负载FGF9和未负载FGF9的电纺纤维即使在血清缺乏的条件下也能支持成纤维细胞增殖五天。在补充FGF9的PEA垫上培养的细胞导致PDGFRβ以浓度和细胞类型依赖性方式上调。
本研究支持从PEA电纺纤维可控释放FGF9用于潜在治疗性血管生成应用的前提。
