Original Article The Effect of Perfluorocarbon-Based Artificial Oxygen Carriers on Tissue-Engineered Trachea Qiang Tan, M.D., 1,2 Ashraf Mohammad El-Badry, M.D., 3,4 Claudio Contaldo, M.D., 5 Rudolf Steiner, M.D., 6 Sven Hillinger, M.D., 7 Manfred Welti, B.Sc., 2 Monika Hilbe, V.M.D., 8 Donat R. Spahn, M.D., 9 Rolf Jaussi, Ph.D., 10 Gustavo Higuera, M.Sc., B.Sc., 11 Clemens A. van Blitterswijk, Ph.D., 11 Qingquan Luo, M.D., 1 and Walter Weder, M.D. 7 The biological effect of the perfluorocarbon-based artificial oxygen carrier (OxygentÔ) was investigated in tissue- engineered trachea (TET) construction. Media supplemented with and without 10% Oxygent were compared in all assessments. Partial tissue oxygen tension (PtO 2 ) was measured with polarographic microprobes; epithelial me- tabolism was monitored by microdialysis inside the TET epithelium perfused with the medium underneath. Chondrocyte–DegraPol Ò constructs were cultured for 1 month with the medium before glycosaminoglycan as- sessment and histology. Tissue reaction of TET epithelial scaffolds immersed with the medium was evaluated on the chick embryo chorioallantoic membrane. Oxygent perfusion medium increased the TET epithelial PtO 2 (51.2  0.3 mm Hg vs. 33.4  0.3 mm Hg at 200 mm thickness; 12.5  0.1 mm Hg vs. 3.1  0.1 mm Hg at 400 mm thickness, p < 0.01) and decreased the lactate concentration (0.63  0.08 vs. 0.80  0.06 mmol=L, p < 0.05), lactate= pyruvate (1.87  0.26 vs. 3.36  10.13, p < 0.05), and lactate=glucose ratios (0.10  0.00 vs. 0.29  0.14, p < 0.05). Chondrocyte–DegraPol in Oxygent group presented lower glycosaminoglycan value (0.03  0.00 vs. 0.13  0.00, p < 0.05); histology slides showed poor acid mucopolysaccharides formation. Orthogonal polarization spectral imaging showed no difference in functional capillary density between the scaffolds cultured on chorioallantoic membranes. The foreign body reaction was similar in both groups. We conclude that Oxygent increases TET epithelial PtO 2 , improves epithelial metabolism, does not impair angiogenesis, and tends to slow cartilage tissue formation. Introduction T he history of trachea replacement dates back to the 19th century, yet till today no clinically convincing method has been established. 1 Tissue engineering has emerged as a promising approach, while hypoxia remains as one of the major obstacles for the success in construction of tissue-engineered trachea (TET). 2,3 During the generation of large-size cell–scaffold constructs, cells near the surface are able to receive sufficient oxygen and nutrients through dif- fusion from immersed medium (in vitro) or from surround- ing tissue fluid (in vivo), whereas cells located in the center are often subjected to detrimental hypoxic conditions. 4–7 Previous studies showed that oxygen delivery by diffusion supports only less than 100-mm-thick tissues, and it is hy- pothesized that continuous medium perfusion may extend these limitations by combining diffusion and convection. 8 Such being the case, in our research of TET we propose an in vivo bioreactor concept defined as implanted tissue- engineered substitutes integrated with an intrascaffold me- dium flow created by an extracorporeal portable pump system for in situ organ regeneration. 8–10 Acting like a topical heart lung machine, the in vivo bioreactor device aims to maintain the survival of preseeded chondrocytes and epithelia until nutritional vessels growing deeply into the TET from surrounding tissues. Through this special design, we aim 1 Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai, China. 2 Laboratory of Tissue Engineering, Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland. 3 Department of Visceral and Transplant Surgery, University Hospital Zurich, Zurich, Switzerland. 4 Department of General Surgery, Sohag Faculty of Medicine, Sohag University Hospital, Sohag University, Sohag, Egypt. 5 Department of Plastic, Reconstructive, and Hand Surgery; 6 Department of Oncology; 7 Department of Thoracic Surgery; University Hospital Zurich, Zurich, Switzerland. 8 FVH (Pathology), ECVP Institute of Veterinary Pathology, Zurich, Switzerland. 9 Institute of Anesthesiology, University Hospital Zurich, Zurich, Switzerland. 10 Biomolecular Research, Paul Scherrer Institute, Villigen PSI, Switzerland. 11 Department of Tissue Regeneration, University of Twente, Enschede, The Netherlands. TISSUE ENGINEERING: Part A Volume 15, Number 9, 2009 ª Mary Ann Liebert, Inc. DOI: 10.1089=ten.tea.2008.0461 2471