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Mucin covalently bonded to microfibers improves the patency of vascular grafts.

ABSTRACT: Due to high incidence of vascular bypass procedures, an unmet need for suitable vessel replacements exists, especially for small-diameter (<6 mm) vascular grafts. Here, we developed a novel, bilayered, synthetic vascular graft of 1-mm diameter that consisted of a microfibrous luminal layer and a nanofibrous outer layer, which was tailored to possess the same mechanical property as native arteries. We then chemically modified the scaffold with mucin, a glycoprotein lubricant on the surface of epithelial tissues, by either passive adsorption or covalent bonding using the di-amino-poly(ethylene glycol) linker to microfibers. Under static and physiological flow conditions, conjugated mucin was more stable than adsorbed mucin on the surfaces. Mucin could slightly inhibit blood clotting, and mucin coating suppressed platelet adhesion on microfibrous scaffolds. In the rat common carotid artery anastomosis model, grafts with conjugated mucin, but not adsorbed mucin, exhibited excellent patency and higher cell infiltration into the graft walls. Mucin, which can be easily obtained from autologous sources, offers a novel method for improving the hemocompatibility and surface lubrication of vascular grafts and many other implants.

SUBMITTER: Janairo RR

PROVIDER: S-EPMC3875147 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Mucin covalently bonded to microfibers improves the patency of vascular grafts.

Janairo Randall Raphael R RR Zhu Yiqian Y Chen Timothy T Li Song S

Tissue engineering. Part A 20131017 1-2

Due to high incidence of vascular bypass procedures, an unmet need for suitable vessel replacements exists, especially for small-diameter (<6 mm) vascular grafts. Here, we developed a novel, bilayered, synthetic vascular graft of 1-mm diameter that consisted of a microfibrous luminal layer and a nanofibrous outer layer, which was tailored to possess the same mechanical property as native arteries. We then chemically modified the scaffold with mucin, a glycoprotein lubricant on the surface of epi ...[more]

PMID: 23962121

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Project description:ObjectiveThe porcine arteriovenous graft model is commonly used to study hemodialysis vascular access failure, with most studies using a bilateral, paired-site approach in either the neck or femoral vessels. In humans, left- and right-sided central veins have different anatomy and diameters, and left-sided central vein catheters have worse outcomes. We assessed the effect of laterality on arteriovenous prosthetic graft patency and hypothesized that left-sided carotid-jugular arteriovenous prosthetic grafts have reduced patency in the porcine model.MethodsArteriovenous polytetrafluoroethylene grafts were placed ipsilaterally or bilaterally in 10 Yorkshire male pigs from the common carotid artery to the internal jugular vein. Ultrasound measurements of blood flow velocities and diameters were assessed before graft placement. Animals were sacrificed at 1 week, 2 weeks, or 3 weeks. Patency was determined clinically; grafts and perianastomotic vessels were excised and analyzed with histology and immunostaining.ResultsAt baseline, left- and right-sided veins and arteries had similar blood flow velocities. Although internal jugular veins had similar diameters at baseline, left-sided carotid arteries had 11% smaller outer diameters (P = .0354). There were 10 left-sided and 8 right-sided polytetrafluoroethylene grafts placed; only 4 of 10 (40%) grafts were patent on the left compared with 7 of 8 (88%) grafts patent on the right (P = .04). Left-sided grafts had increased macrophages at the arterial anastomosis (P = .0007). Left-sided perianastomotic arteries had thicker walls (0.74 vs 0.60 mm; P = .0211) with increased intima-media area (1.14 vs 0.77 mm2; P = .0169) as well as a trend toward 38% smaller luminal diameter (1.6 vs 2.5 mm; P = .0668) and 20% smaller outer diameter (3.0 vs 3.7 mm; P = .0861). Left- and right-sided perianastomotic veins were similar histologically, but left-sided veins had decreased expression of phosphorylated endothelial nitric oxide synthase (P = .0032) and increased numbers of α-actin-positive smooth muscle cells (P = .0022).ConclusionsLeft-sided arteriovenous grafts are associated with reduced short-term patency compared with right-sided grafts in the Yorkshire pig preclinical model of arteriovenous prosthetic grafts. Laterality must be considered in planning and interpreting surgical preclinical models.

Project description:Conventional phase diagram generation involves experimentation to provide an initial estimate of the set of thermodynamically accessible phases and their boundaries, followed by use of phenomenological models to interpolate between the available experimental data points and extrapolate to experimentally inaccessible regions. Such an approach, combined with high throughput first-principles calculations and data-mining techniques, has led to exhaustive thermodynamic databases (e.g. compatible with the CALPHAD method), albeit focused on the reduced set of phases observed at distinct thermodynamic equilibria. In contrast, materials during their synthesis, operation, or processing, may not reach their thermodynamic equilibrium state but, instead, remain trapped in a local (metastable) free energy minimum, which may exhibit desirable properties. Here, we introduce an automated workflow that integrates first-principles physics and atomistic simulations with machine learning (ML), and high-performance computing to allow rapid exploration of the metastable phases to construct "metastable" phase diagrams for materials far-from-equilibrium. Using carbon as a prototypical system, we demonstrate automated metastable phase diagram construction to map hundreds of metastable states ranging from near equilibrium to far-from-equilibrium (400 meV/atom). We incorporate the free energy calculations into a neural-network-based learning of the equations of state that allows for efficient construction of metastable phase diagrams. We use the metastable phase diagram and identify domains of relative stability and synthesizability of metastable materials. High temperature high pressure experiments using a diamond anvil cell on graphite sample coupled with high-resolution transmission electron microscopy (HRTEM) confirm our metastable phase predictions. In particular, we identify the previously ambiguous structure of n-diamond as a cubic-analog of diaphite-like lonsdaelite phase.

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Mucin covalently bonded to microfibers improves the patency of vascular grafts.

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Mucin covalently bonded to microfibers improves the patency of vascular grafts.

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