Said Somiraa S, O'Neil Caroline, Yin Hao, Nong Zengxuan, Pickering J Geoffrey, Mequanint Kibret
1 Biomedical Engineering Graduate Program, The University of Western Ontario , London, Canada .
2 Robarts Research Institute, Schulich School of Medicine and Dentistry, The University of Western Ontario , London, Canada .
Tissue Eng Part A. 2016 Apr;22(7-8):584-96. doi: 10.1089/ten.TEA.2015.0493. Epub 2016 Mar 31.
Therapeutic angiogenesis has emerged as a potential strategy to treat ischemic vascular diseases. However, systemic or local administration of growth factors is usually inefficient for maintaining the effective concentration at the site of interest due to their rapid clearance or degradation. In this study, we report a differential and sustained release of an angiogenic factor, fibroblast growth factor-2 (FGF2), and an arteriogenic factor, fibroblast growth factor-9 (FGF9), from α-amino acid-derived biodegradable poly(ester amide) (PEA) fibers toward targeting neovessel formation and maturation. FGF2 and FGF9 were dual loaded using a mixed blend and emulsion electrospinning technique and exhibited differential and sustained release from PEA fibers over 28 days with preserved bioactivity. In vitro angiogenesis assays showed enhanced endothelial cell (EC) tube formation and directed migration of smooth muscle cells (SMCs) to platelet-derived growth factor (PDGF)-BB and stabilized EC/SMC tube formation. FGF2/FGF9-loaded PEA fibers did not induce inflammatory responses in vitro using human monocytes or in vivo after their subcutaneous implantation into mice. Histological examination showed that FGF2/FGF9-loaded fibers induced cell niche recruitment around the site of implantation. Furthermore, controlled in vivo delivery of FGF9 to mouse tibialis anterior (TA) muscle resulted in a dose-dependent expansion of mesenchymal progenitor-like cell layers and extracellular matrix deposition. Our data suggest that the release of FGF2 and FGF9 from PEA fibers offers an efficient differential and sustained growth factor delivery strategy with relevance to therapeutic angiogenesis.
治疗性血管生成已成为治疗缺血性血管疾病的一种潜在策略。然而，由于生长因子的快速清除或降解，全身或局部施用生长因子通常难以在目标部位维持有效浓度。在本研究中，我们报道了一种血管生成因子成纤维细胞生长因子-2（FGF2）和一种促动脉生成因子成纤维细胞生长因子-9（FGF9）从α-氨基酸衍生的可生物降解聚（酯酰胺）（PEA）纤维中实现差异和持续释放，以靶向新血管的形成和成熟。FGF2和FGF9采用混合共混和乳液静电纺丝技术进行双重负载，并在28天内从PEA纤维中呈现差异和持续释放，同时保留生物活性。体外血管生成试验表明，内皮细胞（EC）管形成增强，平滑肌细胞（SMC）向血小板衍生生长因子（PDGF）-BB定向迁移，并且EC/SMC管形成稳定。负载FGF2/FGF9的PEA纤维在体外使用人单核细胞时或皮下植入小鼠体内后均未诱导炎症反应。组织学检查表明，负载FGF2/FGF9的纤维在植入部位周围诱导细胞龛募集。此外，将FGF9控制性地体内递送至小鼠胫前（TA）肌肉导致间充质祖细胞样细胞层剂量依赖性扩张和细胞外基质沉积。我们的数据表明，FGF2和FGF9从PEA纤维中的释放提供了一种有效的差异和持续生长因子递送策略，与治疗性血管生成相关。
