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Functional growth in tissue-engineered living, vascular grafts: follow-up at 100 weeks in a large animal model


Hoerstrup, S P; Cummings Mrcs, I; Lachat, M; Schoen, F J; Jenni, R; Leschka, S; Neuenschwander, S; Schmidt, D; Mol, A; Günter, C; Gössi, M; Genoni, M; Zund, G (2006). Functional growth in tissue-engineered living, vascular grafts: follow-up at 100 weeks in a large animal model. Circulation, 114(1 Supp):I 159-I 166.

Abstract

BACKGROUND: Living autologous vascular grafts with the capacity for regeneration and growth may overcome the limitations of contemporary artificial prostheses. Particularly in congenital cardiovascular surgery, there is an unmet medical need for growing replacement materials. Here we investigate growth capacity of tissue-engineered living pulmonary arteries in a growing lamb model. METHODS AND RESULTS: Vascular grafts fabricated from biodegradable scaffolds (ID 18+/-l mm) were sequentially seeded with vascular cells. The seeded constructs were grown in vitro for 21 days using biomimetic conditions. Thereafter, these tissue-engineered vascular grafts (TEVGs) were surgically implanted as main pulmonary artery replacements in 14 lambs using cardiopulmonary bypass and followed up for < or = 100 weeks. The animals more than doubled their body weight during the 2-year period. The TEVG showed good functional performance demonstrated by regular echocardiography at 20, 50, 80, and 100 weeks and computed tomography-angiography. In particular, there was no evidence of thrombus, calcification, stenosis, suture dehiscence, or aneurysm. There was a significant increase in diameter by 30% and length by 45%. Histology showed tissue formation reminiscent of native artery. Biochemical analysis revealed cellularity and proteoglycans and increased collagen contents in all of the groups, analogous to those of native vessels. The mechanical profiles of the TEVG showed stronger but less elastic tissue properties than native pulmonary arteries. CONCLUSIONS: This study provides evidence of growth in living, functional pulmonary arteries engineered from vascular cells in a full growth animal model.

BACKGROUND: Living autologous vascular grafts with the capacity for regeneration and growth may overcome the limitations of contemporary artificial prostheses. Particularly in congenital cardiovascular surgery, there is an unmet medical need for growing replacement materials. Here we investigate growth capacity of tissue-engineered living pulmonary arteries in a growing lamb model. METHODS AND RESULTS: Vascular grafts fabricated from biodegradable scaffolds (ID 18+/-l mm) were sequentially seeded with vascular cells. The seeded constructs were grown in vitro for 21 days using biomimetic conditions. Thereafter, these tissue-engineered vascular grafts (TEVGs) were surgically implanted as main pulmonary artery replacements in 14 lambs using cardiopulmonary bypass and followed up for < or = 100 weeks. The animals more than doubled their body weight during the 2-year period. The TEVG showed good functional performance demonstrated by regular echocardiography at 20, 50, 80, and 100 weeks and computed tomography-angiography. In particular, there was no evidence of thrombus, calcification, stenosis, suture dehiscence, or aneurysm. There was a significant increase in diameter by 30% and length by 45%. Histology showed tissue formation reminiscent of native artery. Biochemical analysis revealed cellularity and proteoglycans and increased collagen contents in all of the groups, analogous to those of native vessels. The mechanical profiles of the TEVG showed stronger but less elastic tissue properties than native pulmonary arteries. CONCLUSIONS: This study provides evidence of growth in living, functional pulmonary arteries engineered from vascular cells in a full growth animal model.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Functional Genomics Center Zurich
04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
08 University Research Priority Programs > Systems Biology / Functional Genomics
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2006
Deposited On:08 Dec 2009 12:37
Last Modified:05 Apr 2016 13:37
Publisher:Lippincott Wiliams & Wilkins
ISSN:0009-7322
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1161/CIRCULATIONAHA.105.001172
PubMed ID:16820566
Permanent URL: http://doi.org/10.5167/uzh-25437

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