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One of the main challenges of tissue-engineered vascular prostheses is restenosis due to intimal hyperplasia. The aim of this study is to develop a material for scaffolds able to support cell growth while tolerating physiological conditions and maintaining the patency of carotid artery model. Tubular hyaluronic acid (HA)-functionalized collagen nanofibrous composite scaffolds were prepared by sequential electrospinning method. The tubular composite scaffold has well-controlled biophysical and biochemical signals, providing a good matrix for the adhesion and proliferation of vascular endothelial cells (ECs), but resisting to platelets adhesion when exposed to blood. Carotid artery replacement experiment from 6-week rabbits showed that the HA/collagen nanofibrous composite scaffold grafts with endothelialization on the luminal surface could maintain vascular patency. At retrieval, the composite scaffold maintained good structural integrity and had comparable mechanical strength as the native artery. This study indicating that electrospun scaffolds combined with cells may become an alternative to prosthetic grafts for vascular reconstruction. [ABSTRACT FROM AUTHOR]

In this study, we designed and synthetized artificial vascular scaffolds based on nanofibers of collagen functionalized with hyaluronic acid (HA) in order to direct the phenotypic shape, proliferation, and complete endothelization of mouse primary aortic endothelial cells (PAECs). Layered tubular HA/collagen nanofibers were prepared using electrospinning and crosslinking process. The obtained scaffold is composed of a thin inner layer and a thick outer layer that structurally mimic the layer the intima and media layers of the native blood vessels, respectively. Compared with the pure tubular collagen nanofibers, the surface of HA functionalized collagen nanofibers has higher anisotropic wettability and mechanical flexibility. HA/collagen nanofibers can significantly promote the elongation, proliferation and phenotypic shape expression of PAECs. In vitro co-culture of mouse PAECs and their corresponding smooth muscle cells (SMCs) showed that the luminal endothelialization governs the biophysical integrity of the newly formed extracellular matrix (e.g., collagen and elastin fibers) and structural remodeling of SMCs. Furthermore, in vitro hemocompatibility assays indicated that HA/collagen nanofibers have no detectable degree of hemolysis and coagulation, suggesting their promise as engineered vascular implants. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hyaluronic acid (HA)-functionalized PLA tubular microfibers were designed and synthetized by electrospinning. • The resulting HA/PLA microfibers have no detectable trace of hemolysis and coagulation. • The HA/PLA microfibers promoted vascular endothelial cells proliferation and phenotypic expression. • The tubular HA/PLA based tubular scaffolds enhanced luminal pre-endothelialization of vascular ECs in vitro. This work was designed to evaluate the efficacy of hyaluronic acid (HA) functionalized tubular poly-lactic acid (PLA) microfibers in directing the luminal pre-endothelialization of vascular endothelial cells (ECs). Tubular HA/PLA microfibers with hierarchical architecture were prepared by electrospinning and chemical cross-linking process. A layer of HA microfibrous film coating was fixed on the inner wall surface of the tubular HA/PLA microfibers, resulting in higher anisotropy wettability and relatively lower surface energy and roughness. We confirmed that HA coating on PLA microfibers surface have reduced hemolytic activity and coagulation degree. Mouse vascular ECs exhibited surface-dependent differences in cell elongation and proliferation (HA/PLA > PLA). Compared with PLA microfibers, the gene expression levels of platelet EC adhesion molecule-1 (PECAM-1/CD31) and vascular endothelial growth factor (VEGF) in ECs of HA/PLA microfibers surface were up-regulated. Immunostaining analysis revealed that the surface of HA/PLA nanofibers supported the expression of mature vascular EC phenotype CD31 protein. In vitro co-culture analysis showed that the luminal pre-endothelialization induced vascular smooth muscle cells (SMCs) to maintain their phenotypic shape and establish natural behavior patterns in the hierarchical tubular scaffold. These studies indicate that the biophysical cues of scaffolds are potent regulators of vascular EC endothelialization. [ABSTRACT FROM AUTHOR]