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(Circulation. 2006;114:I-159 – I-166.)
© 2006 American Heart Association, Inc.

Cell Transplantation and Tissue Engineering

Functional Growth in Tissue-Engineered Living, Vascular Grafts

Follow-Up at 100 Weeks in a Large Animal Model

Simon P. Hoerstrup, MD, PhD; Ian Cummings MRCS; Mario Lachat, MD; Frederick J. Schoen, MD, PhD; Rolf Jenni, MD, MSEE; Sebastian Leschka, MD; Stefan Neuenschwander, PhD; Dörthe Schmidt, MD; Anita Mol, PhD; Christina Günter, MD; Mathias Gössi, PhD; Michele Genoni, MD; Gregor Zund, MD

From the Clinic for Cardiovascular Surgery (S.P.H., I.C., M.L., D.S., M.G., G.Z.), Department of Surgical Research (S.P.H., S.N., C.G., G.Z.), University and University Hospital, Zurich, Switzerland; Department of Pathology (F.J.S.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; Departments of Cardiology (R.J.) and Radiology (S.L.), University Hospital Zurich, Switzerland; Department of Biomedical Engineering (A.M.), Technical University Eindhoven, the Netherlands; Department of Polymers (M.G.), Swiss Federal Institute of Technology, Zurich, Switzerland

Correspondence to Simon Philipp Hoerstrup, MD, PhD, Clinic for Cardiovascular Surgery and Department of Surgical Research, University and University Hospital Zurich, Raemistrasse 100, CH 8091 Zurich, Switzerland. E-mail simon_philipp.hoerstrup{at}usz.ch

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 21days 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 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.

Key Words: tissue engineering • growth • pulmonary artery • cells • scaffolds

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