Dataset Information

Tissue-engineered vascular grafts demonstrate evidence of growth and development when implanted in a juvenile animal model.

ABSTRACT:

Introduction

The development of a living, autologous vascular graft with the ability to grow holds great promise for advancing the field of pediatric cardiothoracic surgery.

Objective

To evaluate the growth potential of a tissue-engineered vascular graft (TEVG) in a juvenile animal model.

Methods

Polyglycolic acid nonwoven mesh tubes (3-cm length, 1.3-cm id; Concordia Fibers) coated with a 10% copolymer solution of 50:50 L-lactide and epsilon-caprolactone were statically seeded with 1 x 10 cells/cm autologous bone marrow derived mononuclear cells. Eight TEVGs (7 seeded, 1 unseeded control) were implanted as inferior vena cava (IVC) interposition grafts in juvenile lambs. Subjects underwent bimonthly magnetic resonance angiography (Siemens 1.5 T) with vascular image analysis (www.BioimageSuite.org). One of 7-seeded grafts was explanted after 1 month and all others were explanted 6 months after implantation. Neotissue was characterized using qualitative histologic and immunohistochemical staining and quantitative biochemical analysis.

Results

All grafts explanted at 6 months were patent and increased in volume as measured by difference in pixel summation in magnetic resonance angiography at 1 month and 6 months. The volume of seeded TEVGs at explant averaged 126.9% +/- 9.9% of their volume at 1 month. Magnetic resonance imaging demonstrated no evidence of aneurysmal dilation. TEVG resembled the native IVC histologically and had comparable collagen (157.9 +/- 26.4 microg/mg), elastin (186.9 +/- 16.7 microg/mg), and glycosaminoglycan (9.7 +/- 0.8 microg/mg) contents. Immunohistochemical staining and Western blot analysis showed that Ephrin-B4, a determinant of normal venous development, was acquired in the seeded grafts 6 months after implantation.

Conclusions

TEVGs demonstrate evidence of growth and venous development when implanted in the IVC of a juvenile lamb model.

SUBMITTER: Brennan MP

PROVIDER: S-EPMC2726802 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Publications

Tissue-engineered vascular grafts demonstrate evidence of growth and development when implanted in a juvenile animal model.

Brennan Matthew P MP Dardik Alan A Hibino Narutoshi N Roh Jason D JD Nelson Gregory N GN Papademitris Xenophon X Shinoka Toshiharu T Breuer Christopher K CK

Annals of surgery 20080901 3

<h4>Introduction</h4>The development of a living, autologous vascular graft with the ability to grow holds great promise for advancing the field of pediatric cardiothoracic surgery.<h4>Objective</h4>To evaluate the growth potential of a tissue-engineered vascular graft (TEVG) in a juvenile animal model.<h4>Methods</h4>Polyglycolic acid nonwoven mesh tubes (3-cm length, 1.3-cm id; Concordia Fibers) coated with a 10% copolymer solution of 50:50 L-lactide and epsilon-caprolactone were statically se ...[more]

PMID: 18791357

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Project description:Macrophages are a critical driver of neovessel formation in tissue-engineered vascular grafts (TEVGs), but also contribute to graft stenosis, a leading clinical trial complication. Macrophage depletion via liposomal delivery of clodronate, a first-generation bisphosphonate, mitigates stenosis, but simultaneously leads to a complete lack of tissue development in TEVGs. This result and the associated difficulty of utilizing liposomal delivery means that clodronate may not be an ideal means of preventing graft stenosis. Newer generation bisphosphonates, such as zoledronate, may have differential effects on graft development with more facile drug delivery. We sought to examine the effect of zoledronate on TEVG neotissue formation and its potential application for mitigating TEVG stenosis. Thus, mice implanted with TEVGs received zoledronate or no treatment and were monitored by serial ultrasound for graft dilation and stenosis. After two weeks, TEVGs were explanted for histological examination. The overall graft area and remaining graft material (polyglycolic-acid) were higher in the zoledronate treatment group. These effects were associated with a corresponding decrease in macrophage infiltration. In addition, zoledronate affected the deposition of collagen in TEVGs, specifically, total and mature collagen. These differences may be, in part, explained by a depletion of leukocytes within the bone marrow that subsequently led to a decrease in the number of tissue-infiltrating macrophages. TEVGs from zoledronate-treated mice demonstrated a significantly greater degree of smooth muscle cell presence. There was no statistical difference in graft patency between treatment and control groups. While zoledronate led to a decrease in the number of macrophages in the TEVGs, the severity of stenosis appears to have increased significantly. Zoledronate treatment demonstrates that the process of smooth muscle cell-mediated neointimal hyperplasia may occur separately from a macrophage-mediated mechanism.

Dataset Information

Tissue-engineered vascular grafts demonstrate evidence of growth and development when implanted in a juvenile animal model.

Introduction

Objective

Methods

Results

Conclusions

Publications

Tissue-engineered vascular grafts demonstrate evidence of growth and development when implanted in a juvenile animal model.

Similar Datasets

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