Abstract
The field of therapeutic angiogenesis has been predominantly concentrated in modalities that incorporate pro-angiogenic growth factors and/or cells within polymeric constructs that are implanted into the ischemic region. There is growing evidence that construct architecture can significantly affect growth factor activity, cellular viability and differentiation potential. Electrospinning is an attractive but simple scaffold fabrication technique that offers several advantages over traditional fabrication approaches to prepare highly organized structures for therapeutic angiogenesis applications. We recently described the fabrication of nanofibrous scaffolds with aligned fiber orientation that directed cell migration and orientation (i.e.human umbilical vein endothelial cells). Herein we demonstrate the ability of bFGF containing nanofibrous gelatin B scaffolds with controlled fiber orientation to promote capillary formation in vivo. Aligned scaffolds loaded with bFGF induced the highest levels of reperfusion (73% increased in LDPI ratios by day 21 post ischemia induction) in comparison to all other groups including scaffolds with random fiber orientation. Furthermore, the newly formed vasculature, assessed by confocal microscopy, had a parallel alignment along the axis of the scaffold’s fibers. In contrast, no vessel directionality was observed in the animals treated with scaffolds with random fiber orientation in the presence or absence of bFGF.
Highlights
Diseases that result in ischemia due to vascular occlusions are the leading causes of morbidity and mortality in western societies despite improvements in minimally invasive surgical interventions to reestablish proper blood flow in underperfused regions of the heart and legs
Qian et al demonstrated that endothelial cells seeded onto aligned nanofibrous scaffolds in contrast to those seeded onto randomly deposited nanofibrous scaffolds, preserved the expression of platelet-endothelial cell adhesion molecule 1 (PECAM-1), intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) [18]
Similar results have been reported for smooth muscle cells (SMCs) [20] and human aortic endothelial cells (HAECs) [21] in which scaffold architecture was able to induce desired cellular morphology and preserve desired cell markers
Summary
Diseases that result in ischemia due to vascular occlusions are the leading causes of morbidity and mortality in western societies despite improvements in minimally invasive surgical interventions to reestablish proper blood flow in underperfused regions of the heart and legs. Ma et al documented the orientation of endothelial cells (ECs) to be parallel to the direction of the nanofiber alignment, in contrast to the random cellular orientation seen in randomly deposited nanofibrous scaffolds [3]. Kumar et al reported the effects of different scaffold architectures on primary human bone marrow stromal cells (hBMSCs) [19]. They demonstrated the ability of scaffold architecture and structure to dictate cell morphology and induce unique gene expressions. Similar results have been reported for smooth muscle cells (SMCs) [20] and human aortic endothelial cells (HAECs) [21] in which scaffold architecture was able to induce desired cellular morphology and preserve desired cell markers. The cells, following seven days of culturing, maintained phenotypic cell markers (i.e. CD146, VE-Cadherin, PECAM-1 and vWF) and formed short cord-like structures that began to interconnect and form a network of capillaries with identifiable lumens [21]
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