Axially aligned nanofibrous matrices were evaluated as small diameter cardiovascular grafts. Grafts were prepared using the poly(L-lactic acid) (PLA) and poly(ε-caprolactone) (PCL) physical blends in the ratios of 75:25 and 25:75 with the dimension of (40 × 0.2 × 4) millimeter by electrospinning using dynamic collector (1500 RPM). Hydrophobicity and tensile stress were significantly higher in PLA-PCL (75:25), whereas tensile strain and fiber density were significantly higher in PLA-PCL (25:75). Properties such as anastomatic strength porosity, average pore size, degradation with retained fiber orientation, and thromboresistivity were comparable between blends. Human umbilical vascular endothelial cells (HUVEC) adhesion on the scaffolds was observed within 24 h. Cell viability and proliferation were rationally influenced by the aligned nanofibers. Gene expression reveals the grafts thromboresistivity, elasticity, and aided neovascularization. Thus, these scaffolds could be an ideal candidate for small diameter blood vessel engineering.

Regeneration of functional small diameter blood vessels still remains a challenge, as the synthetic vascular grafts fail to mimic the complex structural architecture and dynamic functions of blood vessels and also lack with the lack of non-thrombogenicity. Although, the existence of nanofibrous extracellular matrix components in the native tissue promotes many physical and molecular signals to the endothelial cells for the regulation of morphogenesis, homeostasis, and cellular functions in vascular tissue, poor understanding of the structural architecture on the functional activation of appropriate genes limits the development of successful vascular graft design. Hence, the present review outlines the functional contributions of various nanofibrous extracellular matrix components in native blood vessels. Further, the review focuses on the role of nanofiber topography of biomaterial scaffolds in endothelial cell fate processes such as adhesion, proliferation, migration, and infiltration with the expression of vasculature specific genes; thereby allowing the reader to envisage the communication between the nano-architecture of scaffolds and endothelial cells in engineering small diameter vascular grafts.

Biodegradable polymers have been extensively used as scaffolds to regenerate lost tissues. The geometry of the three-dimensional (3D) scaffolds has an influence on the cellular behaviour. In this study, we have developed 3D-scaffolds of axially aligned nanofibres of poly(lactic acid) (PLA), poly(caprolactone) (PCL) and PLA:CL (50:50) with diameters in the range 100-400 nm, internal diameter 4 mm, length 4 cm and wall thickness 0.2 mm, by using a dynamic collector. PCL and PLA:CL nanofibres were significantly less hydrophobic than PLA nanofibres. The porosity of PCL (16.23 ± 9.88%) and PLA:CL nanofibres (14.77 ± 3.41%) were comparable, while PLA (6.57 ± 1.54%) nanofibres had lower porosity. The tensile strength and Young's modulus of PLA was significantly lower than PCL and PLA:CL nanofibres and the suture retention strengths of all three scaffolds were comparable. After 4 weeks, the molecular weight of PLA nanofibres was reduced by 53% compared to 44% and 41% for PCL and the PLA:CL nanofibres, respectively. However, the PLA:CL nanofibres maintained their structural integrity even after 28 days. Platelet adhesion studies showed that PCL nanofibres had least tendency to be thrombogenic, while PLA:CL blend nanofibres were highly thrombogenic. Further, in vitro responses such as cell adhesion, proliferation and gene expression of human umbilical vascular endothelial cells (HUVECs) were evaluated. After 6 days of culture, the surfaces of all the three scaffolds were completely covered with cells. Our results demonstrate that expression levels of elastin, angiopoietin, laminin-4α and -5α were upregulated in PCL and PLA:CL nanofibres without the addition of any exogenous factors.