Differential outcomes of venous and arterial tissue engineered vascular grafts highlight the importance of coupling long-term implantation studies with computational modeling.

Electrospinning is commonly used to generate polymeric scaffolds for tissue engineering. Using this approach, we developed a small-diameter tissue engineered vascular graft (TEVG) composed of poly-ε-caprolactone-co-l-lactic acid (PCLA) fibers and longitudinally assessed its performance within both the venous and arterial circulations of immunodeficient (SCID/bg) mice. Based on in vitro analysis demonstrating complete loss of graft strength by 12 weeks, we evaluated neovessel formation in vivo over 6-, 12- and 24-week periods.

Magnetic Resonance Imaging of Shear Stress and Wall Thickness in Tissue-Engineered Vascular Grafts.

Objectives: Tissue-engineered vascular grafts (TEVGs) have demonstrated potential for treating congenital heart disease (CHD); however, quantitative imaging for tracking functional and structural remodeling of TEVGs has not been applied. Therefore, we evaluated the potential of magnetic resonance (MR) imaging for assessing TEVG wall shear stress (WSS) and wall thickness in a large animal model.

Methods: Cell-seeded (n = 3) or unseeded (n = 3) TEVGs were implanted as inferior vena cava interposition grafts in juvenile lambs.

Engineered Tissue-Stent Biocomposites as Tracheal Replacements.

Here we report the creation of a novel tracheal construct in the form of an engineered, acellular tissue-stent biocomposite trachea (TSBT). Allogeneic or xenogeneic smooth muscle cells are cultured on polyglycolic acid polymer-metal stent scaffold leading to the formation of a tissue comprising cells, their deposited collagenous matrix, and the stent material. Thorough decellularization then produces a final acellular tubular construct.

Biomimetic Culture Reactor for Whole-Lung Engineering.

Decellularized organs are now established as promising scaffolds for whole-organ regeneration. For this work to reach therapeutic practice, techniques and apparatus are necessary for doing human-scale clinically applicable organ cultures. We have designed and constructed a bioreactor system capable of accommodating whole human or porcine lungs, and we describe in this study relevant technical details, means of assembly and operation, and validation.

PPAR-γ agonist attenuates inflammation in aortic aneurysm patients.

Background And Objective: Peroxisome proliferator-activated receptor (PPAR) -γ agonist, which is an anti-diabetes drug and reduces expression of tumor necrosis factor (TNF)-α, reported to have the effects for anti-inflammation in our body. In cardiovascular fields, this PPAR-γ agonist already reported to suppress progression of coronary atherosclerosis. Various cytokines, which is secreted from fat tissues around artery, promote atherosclerosis and/or aneurysmal changes in aorta/artery.

Development of small diameter nanofiber tissue engineered arterial grafts.

The surgical repair of heart and vascular disease often requires implanting synthetic grafts. While synthetic grafts have been successfully used for medium-to-large sized arteries, applications for small diameter arteries (<6 mm) is limited due to high rates of occlusion by thrombosis. Our objective was to develop a tissue engineered vascular graft (TEVG) for small diameter arteries.

Well-organized neointima of large-pore poly(L-lactic acid) vascular graft coated with poly(L-lactic-co-ε-caprolactone) prevents calcific deposition compared to small-pore electrospun poly(L-lactic acid) graft in a mouse aortic implantation model.

Objective: Tissue engineering techniques have emerged that allow bioresorbable grafts to be implanted that restore function and transform into biologically active arteries. However, these implants are susceptible to calcification during the remodeling process. The objective of this study was to evaluate the role of pore size of bioabsorbable grafts in the development of calcification.

Efficient intratracheal delivery of airway epithelial cells in mice and pigs.

Cellular therapy via direct intratracheal delivery has gained interest as a novel therapeutic strategy for treating various pulmonary diseases including cystic fibrosis lung disease. However, concerns such as insufficient cell engraftment in lungs and lack of large animal model data remain to be resolved. This study aimed to establish a simple method for evaluating cell retention in lungs and to develop reproducible approaches for efficient cell delivery into mouse and pig lungs.

Comparison of the biological equivalence of two methods for isolating bone marrow mononuclear cells for fabricating tissue-engineered vascular grafts.

Our approach for fabricating tissue-engineered vascular grafts (TEVG), applied in the surgical management of congenital heart disease, is accomplished by seeding isolated bone marrow-derived mononuclear cells (BM-MNCs) onto biodegradable scaffolds. The current method used for isolation of BM-MNCs is density centrifugation in Ficoll. This is a time-consuming, labor-intensive, and operator-dependent method.

Targeted imaging of matrix metalloproteinase activity in the evaluation of remodeling tissue-engineered vascular grafts implanted in a growing lamb model.

Objectives: The clinical translation of tissue-engineered vascular grafts has been demonstrated in children. The remodeling of biodegradable, cell-seeded scaffolds to functional neovessels has been partially attributed to matrix metalloproteinases. Noninvasive assessment of matrix metalloproteinase activity can indicate graft remodeling and elucidate the progression of neovessel formation.

Comparison of a closed system to a standard open technique for preparing tissue-engineered vascular grafts.

We developed a prototype for a closed apparatus for assembling tissue-engineered vascular grafts (TEVGs) with the goal of creating a simple operator-independent method for making TEVGs to optimize safety and enable widespread application of this technology. The TEVG is made by seeding autologous bone marrow-derived mononuclear cells onto a biodegradable tubular scaffold and is the first man-made vascular graft to be successfully used in humans. A critical barrier, which has prevented the widespread clinical adoption of the TEVG, is that cell isolation, scaffold seeding, and incubation are performed using an open method.

In vivo applications of electrospun tissue-engineered vascular grafts: a review.

There is great clinical demand for synthetic vascular grafts with improved long-term efficacy. The ideal vascular conduit is easily implanted, nonthrombogenic, biocompatible, resists aneurysmal dilatation, and ultimately degrades or is assimilated as the patient remodels the graft into tissue resembling native vessel. The field of vascular tissue engineering offers an opportunity to design the ideal synthetic graft, and researchers have evaluated a variety of methods and materials for use in graft construction.

Evaluation of remodeling process in small-diameter cell-free tissue-engineered arterial graft.

Objective: Autologous grafts are used to repair atherosclerotic cardiovascular diseases; however, many patients lack suitable donor graft tissue. Recently, tissue engineering techniques have emerged to make biologically active blood vessels. We applied this technique to produce arterial grafts using established biodegradable materials without cell seeding.

Vessel bioengineering.

The development of vascular bioengineering has led to a variety of novel treatment strategies for patients with cardiovascular disease. Notably, combining biodegradable scaffolds with autologous cell seeding to create tissue-engineered vascular grafts (TEVG) allows for in situ formation of organized neovascular tissue and we have demonstrated the clinical viability of this technique in patients with congenital heart defects. The role of the scaffold is to provide a temporary 3-dimensional structure for cells, but applying TEVG strategy to the arterial system requires scaffolds that can also endure arterial pressure.