School of Biomedical Engineering, Western University, London, Ontario, N6A 5B9, Canada.
Robarts Research Institute, Western University, London, Ontario, N6A 5B7, Canada.
Adv Healthc Mater. 2019 Apr;8(8):e1801294. doi: 10.1002/adhm.201801294. Epub 2019 Feb 20.
Delivery of angiogenic growth factors lessens ischemia in preclinical models but has demonstrated little benefit in patients with peripheral vascular disease. Augmenting the wrapping of nascent microvessels by mural cells constitutes an alternative strategy to regenerating a functional microvasculature, particularly if integrated with a sustained delivery platform. Herein, electrospun poly(ester amide) (PEA) nanofiber mats are fabricated for delivering a mural cell-targeting factor, fibroblast growth factor 9 (FGF9). Proof-of-principle is established by placing FGF9/FGF2-loaded PEA fiber mats on the chick chorioallantoic membrane and identifying enhanced angiogenesis by 3D power Doppler micro-ultrasound imaging. To assess the delivery system in ischemic muscle, FGF9-loaded PEA fiber mats are implanted onto the surface of the tibialis anterior muscle of mice with hindlimb ischemia. The system supplies FGF9 into the tibialis anterior muscle and yields a neo-microvascular network with enhanced mural cell coverage up to 28 days after injury. The regenerating muscle that receives FGF9 display near-normal sized myofibers and reduced interstitial fibrosis. Moreover, the mice demonstrate improved locomotion. These findings of locally released FGF9 from PEA nanofibers raise prospects for a microvascular remodeling approach to improve muscle health in peripheral vascular disease.
在临床前模型中，血管生成生长因子的传递可以减轻缺血，但在周围血管疾病患者中，其益处甚微。通过壁细胞包裹新生微血管是一种再生功能性微血管的替代策略，特别是如果与持续传递平台相结合。在此，制备了用于递送壁细胞靶向因子成纤维细胞生长因子 9（FGF9）的电纺聚（酯酰胺）（PEA）纳米纤维垫。通过将负载 FGF9/FGF2 的 PEA 纤维垫放置在鸡胚绒毛尿囊膜上，并通过 3D 功率多普勒微超声成像来鉴定增强的血管生成，从而证明了这一原理。为了评估在缺血肌肉中的递药系统，将负载 FGF9 的 PEA 纤维垫植入患有后肢缺血的小鼠的胫骨前肌表面。该系统将 FGF9 输送到胫骨前肌中，并在损伤后 28 天内产生具有增强的壁细胞覆盖的新微血管网络。接收 FGF9 的再生肌肉显示出接近正常大小的肌纤维和减少的间质纤维化。此外，小鼠的运动能力得到改善。这些源自 PEA 纳米纤维的局部释放 FGF9 的发现为改善周围血管疾病中肌肉健康的微血管重塑方法提供了前景。
