Bioengineered human acellular vessels recellularize and evolve into living blood vessels after human implantation.

Traditional vascular grafts constructed from synthetic polymers or cadaveric human or animal tissues support the clinical need for readily available blood vessels, but often come with associated risks. Histopathological evaluation of these materials has shown adverse host cellular reactions and/or mechanical degradation due to insufficient or inappropriate matrix remodeling. We developed an investigational bioengineered human acellular vessel (HAV), which is currently being studied as a hemodialysis conduit in patients with end-stage renal disease.

Clinical Outcomes of Arteriovenous Access in Incident Hemodialysis Patients with Medicare Coverage, 2012-2014.

Background: Chronic hemodialysis requires a mode of vascular access through an arteriovenous fistula (AVF), a prosthetic arteriovenous graft (AVG), or a central venous catheter (CVC). AVF is recommended over AVG or CVC due to increased patency and decreased intervention rates for those that mature. AVG are preferred over CVC due to decreased infection and mortality risk.

Susceptibility of ePTFE vascular grafts and bioengineered human acellular vessels to infection.

Background: Synthetic expanded polytetrafluorethylene (ePTFE) grafts are routinely used for vascular repair and reconstruction but prone to sustained bacterial infections. Investigational bioengineered human acellular vessels (HAVs) have shown clinical success and may confer lower susceptibility to infection. Here we directly compared the susceptibility of ePTFE grafts and HAV to bacterial contamination in a preclinical model of infection.

What is the greatest regulatory challenge in the translation of biomaterials to the clinic?

Leaders in the field comment on what they perceive to be the greatest barriers to biomaterial translation.

Bioengineered vascular grafts: can we make them off-the-shelf?

Surgical treatments for vascular disease have progressed during the past century from autologous bypass conduits to synthetic materials, animal-derived tissues, cryopreserved grafts, and, finally, bioengineered conduits. In all cases, alternative vascular grafting materials have been developed with the goal of treating patients who have severe vascular disease requiring bypass but who have no suitable autologous conduit. Synthetic vascular grafts, animal-derived tissues, and cryopreserved grafts all have drawbacks in terms of availability and functionality that have limited their routine clinical adoption.

An early study on the mechanisms that allow tissue-engineered vascular grafts to resist intimal hyperplasia.

Intimal hyperplasia is one of the prominent failure mechanisms for arteriovenous fistulas and arteriovenous access grafts. Human tissue-engineered vascular grafts (TEVGs) were implanted as arteriovenous grafts in a novel baboon model. Ultrasound was used to monitor flow rates and vascular diameters throughout the study.

Readily available tissue-engineered vascular grafts.

Autologous or synthetic vascular grafts are used routinely for providing access in hemodialysis or for arterial bypass in patients with cardiovascular disease. However, some patients either lack suitable autologous tissue or cannot receive synthetic grafts. Such patients could benefit from a vascular graft produced by tissue engineering.

Effects of mechanical stretch on collagen and cross-linking in engineered blood vessels.

It has been shown that mechanical stimulation affects the physical properties of multiple types of engineered tissues. However, the optimum regimen for applying cyclic radial stretch to engineered arteries is not well understood. To this end, the effect of mechanical stretch on the development of engineered blood vessels was analyzed in constructs grown from porcine vascular smooth muscle cells.

A microstructurally motivated model of the mechanical behavior of tissue engineered blood vessels.

Mechanical models have potential to guide the development and use of engineered blood vessels as well as other engineered tissues. This paper presents a microstructurally motivated, pseudoelastic, mechanical model of the biaxial mechanics of engineered vessels in the physiologic pressure range. The model incorporates experimentally measured densities and alignments of engineered collagen.

An ultrastructural analysis of collagen in tissue engineered arteries.

Collagen is the structural molecule that is most correlated with strength in blood vessels. In this study, we compared the properties of collagen in engineered and native blood vessels. Transmission electron microscopy (TEM) was used to image sections of engineered and native arteries.

Mechanical properties and compositions of tissue engineered and native arteries.

With the goal of mimicking the mechanical properties of a given native tissue, tissue engineers seek to culture replacement tissues with compositions similar to those of native tissues. In this report, differences between the mechanical properties of engineered arteries and native arteries were correlated with differences in tissue composition. Engineered arteries failed to match the strengths or compliances of native tissues.

Feasibility of vitrification as a storage method for tissue-engineered blood vessels.

It is well established that, in multicellular systems, conventional cryopreservation results in damaging ice formation, both in the cells and in the surrounding extracellular matrix. As an alternative to conventional cryopreservation, we performed a feasibility study using vitrification (ice-free cryopreservation) to cryopreserve tissue-engineered blood vessels. Fresh, frozen, and vitrified tissue-engineered blood vessels were compared using histological methods, cellular viability, and mechanical properties.

Effects of copper and cross-linking on the extracellular matrix of tissue-engineered arteries.

In many cases, the mechanical strengths of tissue-engineered arteries do not match the mechanical strengths of native arteries. Ultimate arterial strength is primarily dictated by collagen in the extracellular matrix. but collagen in engineered arteries is not as dense, as organized, or as mature as collagen in native arteries.

Effects of copper and cross-linking on the extracellular matrix of tissue-engineered arteries.

In many cases, the mechanical strengths of tissue-engineered arteries do not match the mechanical strengths of native arteries. Ultimate arterial strength is primarily dictated by collagen in the extracellular matrix, but collagen in engineered arteries is not as dense, as organized, or as mature as collagen in native arteries. One step in the maturation process of collagen is the formation of hydroxylysyl pyridinoline (HP) cross-links between and within collagen molecules.

Blood vessels engineered from human cells.

Tissue engineering has made considerable progress in the past decade, but advances have stopped short of clinical application for most tissues. We postulated that an obstacle in engineering human tissues is the limited replicative capacity of adult somatic cells. To test this hypothesis, the effectiveness of telomerase expression to extend cellular lifespan was assessed in a model of human vascular tissue engineering.

Decellularized native and engineered arterial scaffolds for transplantation.

More than 570,000 coronary artery bypass grafts are implanted each year, creating an important demand for small-diameter vascular grafts. For patients who lack adequate internal mammary artery or saphenous vein, tissue-engineered arteries may prove useful. However, the time needed to tissue engineer arteries (7 weeks or more) is too long for many patients.

Decellularized Native and Engineered Arterial Scaffolds for Transplantation.

More than 570,000 coronary artery bypass grafts are implanted each year, creating an important demand for small-diameter vascular grafts. For patients who lack adequate internal mammary artery or saphenous vein, tissue-engineered arteries may prove useful. However, the time needed to tissue engineer arteries (7 weeks or more) is too long for many patients.