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J Thorac Cardiovasc Surg 2004;128:900-906
© 2004 The American Association for Thoracic Surgery

General Thoracic Surgery

Experimental generation of a tissue-engineered functional and vascularized trachea

Thorsten Walles, MDa,,b, Bettina Giereb, Michael Hofmann, PhDc, Johanna Schanzb, Fred Hofmann, PhDd, Heike Mertsching, PhDb, Paolo Macchiarini, MD, PhDa,,b,*

a General Thoracic Surgery Biological Laboratory
b the Tissue Engineering Network
c Department of Nuclear Medicine
d Department of Toxicology Hannover Medical School, Hannover, Germany

Received for publication April 26, 2004; revisions received July 13, 2004; accepted for publication July 21, 2004.

* Address for reprints: Paolo Macchiarini, MD, PhD, Department of Thoracic and Vascular Surgery, Heidehaus Hospital, Hannover Medical School, Am Leineufer 70, D-30419 Hannover, Germany (E-mail: pmacchiarini{at}compuserve.com).

OBJECTIVE: We sought to grow in vitro functional smooth muscle cells, chondrocytes, and respiratory epithelium on a biologic, directly vascularized matrix as a scaffold for tracheal tissue engineering.

METHODS: Ten- to 15-cm–long free jejunal segments with their own vascular pedicle were harvested and acellularized from donor pigs (n = 10) and used as a vascular matrix. Autologous costal chondrocytes, smooth muscle cells, and respiratory epithelium and endothelial progenitor cells were first cultured in vitro and then disseminated on the previously acellularized vascular matrix. Histologic, immunohistologic, molecular imaging, and Western blotting studies were then performed to assess cell viability.

RESULTS: The endothelial progenitor cells re-endothelialized the matrix to such an extent that endothelial cell viability was uniformly documented through 2-(18F)-fluoro-2'-deoxyglucose positron emission tomography. This vascularized scaffold was seeded with functional (according to Western blot analysis) smooth muscle cells and successfully reseeded with viable ciliated respiratory epithelium. Chondrocyte growth and production of extracellular cartilaginous matrix was observed as soon as 2 weeks after their culture.

CONCLUSIONS: The fundamental elements for a bioartificial trachea were successfully engineered in vitro in a direct vascularized 10- to 15-cm–long bioartificial matrix. Future experimental work will be directed to give them a 3-dimensional aspect and a biomechanical profile of a functioning trachea.




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