Annals of Biomedical Engineering

, Volume 39, Issue 8, pp 2091–2113 | Cite as

Overview of Tracheal Tissue Engineering: Clinical Need Drives the Laboratory Approach

  • Lindsey M. Ott
  • Robert A. Weatherly
  • Michael S. Detamore


Breathing is a natural function that most of us do not even think about, but for those who suffer from disease or damage of the trachea, the obstruction of breathing can mean severe restrictions to quality of life or may even be fatal. Replacement and reconstruction of the trachea is one of the most difficult procedures in otolaryngology/head and neck surgery, and also one of the most vital. Previous reviews have focused primarily on clinical perspectives or instead on engineering strategies. However, the current review endeavors to bridge this gap by evaluating engineering approaches in a practical clinical context. For example, although contemporary approaches often include in vitro bioreactor pre-culture, or sub-cutaneous in vivo conditioning, the limitations they present in terms of regulatory approval, cost, additional surgery, and/or risk of infection challenge engineers to develop the next generation of biodegradable/resorbable biomaterials that can be directly implanted in situ. Essentially, the functionality of the replacement is the most important requirement. It must be the correct shape and size, achieve an airtight fit, resist collapse as it is replaced by new tissue, and be non-immunogenic. As we look to the future, there will be no one-size-fits-all solution.


Tracheal reconstruction Windpipe Tissue engineering Airway Regenerative medicine 


  1. 1.
    Asnaghi, A., P. Macchiarini, and S. Mantero. Tissue engineering toward organ replacement: a promising approach in airway transplant. Int. J. Artif. Organs 32:763–768, 2009.PubMedGoogle Scholar
  2. 2.
    Bader, A., and P. Macchiarini. Moving towards in situ tracheal regeneration: the bionic tissue engineered transplantation approach. J. Cell Mol. Med. 14:1877–1889, 2010.PubMedCrossRefGoogle Scholar
  3. 3.
    Baiguera, S., M. A. Birchall, and P. Macchiarini. Tissue-engineered tracheal transplantation. Transplantation 89:485–491, 2010.PubMedCrossRefGoogle Scholar
  4. 4.
    Barry, C. Doctors: Transplant Advance in Windpipe Cancer. Associated Press. July 30, 2010. URL:
  5. 5.
    Bucheler, M., and A. Haisch. Tissue engineering in otorhinolaryngology. DNA Cell Biol. 22:549–564, 2003.PubMedCrossRefGoogle Scholar
  6. 6.
    Coraux, C., B. Nawrocki-Raby, J. Hinnrasky, C. Kileztky, D. Gaillard, C. Dani, and E. Puchelle. Embryonic stem cells generate airway epithelial tissue. Am. J. Respir. Cell Mol. Biol. 32:87–92, 2005.PubMedCrossRefGoogle Scholar
  7. 7.
    Delaere, P. Stem-cell “hype” in tracheal transplantation? Transplantation 90:927–928, 2010; (author reply 928–929).PubMedCrossRefGoogle Scholar
  8. 8.
    Delaere, P., J. Vranckx, G. Verleden, P. De Leyn, and D. Van Raemdonck. Tracheal allotransplantation after withdrawal of immunosuppressive therapy. N. Engl. J. Med. 362:138–145, 2010.PubMedCrossRefGoogle Scholar
  9. 9.
    Doolin, E. J., L. F. Strande, X. Sheng, and C. W. Hewitt. Engineering a composite neotrachea with surgical adhesives. J. Pediatr. Surg. 37:1034–1037, 2002.PubMedCrossRefGoogle Scholar
  10. 10.
    Dormer, N. H., M. Singh, L. Wang, C. J. Berkland, and M. S. Detamore. Osteochondral interface tissue engineering using macroscopic gradients of bioactive signals. Ann. Biomed. Eng. 38:2167–2182, 2010.PubMedCrossRefGoogle Scholar
  11. 11.
    Doss, A. E., S. S. Dunn, K. A. Kucera, L. A. Clemson, and J. B. Zwischenberger. Tracheal replacements: Part 2. ASAIO J. 53:631–639, 2007.PubMedCrossRefGoogle Scholar
  12. 12.
    Fuchs, J. R., D. Hannouche, S. Terada, J. P. Vacanti, and D. O. Fauza. Fetal tracheal augmentation with cartilage engineered from bone marrow-derived mesenchymal progenitor cells. J. Pediatr. Surg. 38:984–987, 2003.PubMedCrossRefGoogle Scholar
  13. 13.
    Fuchs, J. R., S. Terada, E. R. Ochoa, J. P. Vacanti, and D. O. Fauza. Fetal tissue engineering: in utero tracheal augmentation in an ovine model. J. Pediatr. Surg. 37:1000–1006, 2002; (discussion 1000–1006).PubMedCrossRefGoogle Scholar
  14. 14.
    Gerek, M. Laryngotracheal reconstruction update. Curr. Opin. Otolaryngol. Head Neck Surg. 9:209–213, 2001.CrossRefGoogle Scholar
  15. 15.
    Gilbert, T. W., S. Gilbert, M. Madden, S. D. Reynolds, and S. F. Badylak. Morphologic assessment of extracellular matrix scaffolds for patch tracheoplasty in a canine model. Ann. Thorac. Surg. 86:967–974, 2008; (discussion 967–974).PubMedCrossRefGoogle Scholar
  16. 16.
    Gilpin, D. A., M. S. Weidenbecher, and J. E. Dennis. Scaffold-free tissue-engineered cartilage implants for laryngotracheal reconstruction. Laryngoscope 120:612–617, 2010.PubMedCrossRefGoogle Scholar
  17. 17.
    Go, T., P. Jungebluth, S. Baiguero, A. Asnaghi, J. Martorell, H. Ostertag, S. Mantero, M. Birchall, A. Bader, and P. Macchiarini. Both epithelial cells and mesenchymal stem cell-derived chondrocytes contribute to the survival of tissue-engineered airway transplants in pigs. J. Thorac. Cardiovasc. Surg. 139:437–443, 2010.PubMedCrossRefGoogle Scholar
  18. 18.
    Goto, Y., Y. Noguchi, A. Nomura, T. Sakamoto, Y. Ishii, S. Bitoh, C. Picton, Y. Fujita, T. Watanabe, S. Hasegawa, and Y. Uchida. In vitro reconstitution of the tracheal epithelium. Am. J. Respir. Cell Mol. Biol. 20:312–318, 1999.PubMedGoogle Scholar
  19. 19.
    Grillo, H. C. Tracheal replacement: a critical review. Ann. Thorac. Surg. 73:1995–2004, 2002.PubMedCrossRefGoogle Scholar
  20. 20.
    Grillo, H. C. Development of tracheal surgery: a historical review. Part 1: techniques of tracheal surgery. Ann. Thorac. Surg. 75:610–619, 2003.PubMedCrossRefGoogle Scholar
  21. 21.
    Grillo, H. C. Tracheal replacement. J. Thorac. Cardiovasc. Surg. 125:975, 2003.PubMedGoogle Scholar
  22. 22.
    Grimmer, J. F., C. B. Gunnlaugsson, E. Alsberg, H. S. Murphy, H. J. Kong, D. J. Mooney, and R. A. Weatherly. Tracheal reconstruction using tissue-engineered cartilage. Arch. Otolaryngol. Head Neck Surg. 130:1191–1196, 2004.PubMedCrossRefGoogle Scholar
  23. 23.
    Henderson, J. H., J. F. Welter, J. M. Mansour, C. Niyibizi, A. I. Caplan, and J. E. Dennis. Cartilage tissue engineering for laryngotracheal reconstruction: comparison of chondrocytes from three anatomic locations in the rabbit. Tissue Eng. 13:843–853, 2007.PubMedCrossRefGoogle Scholar
  24. 24.
    Holt, P. G., M. A. Schon-Hegrad, M. J. Phillips, and P. G. McMenamin. Ia-positive dendritic cells form a tightly meshed network within the human airway epithelium. Clin. Exp. Allergy 19:597–601, 1989.PubMedCrossRefGoogle Scholar
  25. 25.
    Igai, H., S. S. Chang, M. Gotoh, Y. Yamamoto, M. Yamamoto, Y. Tabata, and H. Yokomise. Tracheal cartilage regeneration and new bone formation by slow release of bone morphogenetic protein (BMP)-2. ASAIO J. 54:104–108, 2008.PubMedCrossRefGoogle Scholar
  26. 26.
    Jungebluth, P., T. Go, A. Asnaghi, S. Bellini, J. Martorell, C. Calore, L. Urbani, H. Ostertag, S. Mantero, M. T. Conconi, and P. Macchiarini. Structural and morphologic evaluation of a novel detergent-enzymatic tissue-engineered tracheal tubular matrix. J. Thorac. Cardiovasc. Surg. 138:586–593, 2009; (discussion 592–593).PubMedCrossRefGoogle Scholar
  27. 27.
    Kalathur, M., S. Baiguera, and P. Macchiarini. Translating tissue-engineered tracheal replacement from bench to bedside. Cell. Mol. Life Sci. 67(24):4185–4196, 2010.PubMedCrossRefGoogle Scholar
  28. 28.
    Kamil, S. H., R. D. Eavey, M. P. Vacanti, C. A. Vacanti, and C. J. Hartnick. Tissue-engineered cartilage as a graft source for laryngotracheal reconstruction: a pig model. Arch. Otolaryngol. Head Neck Surg. 130:1048–1051, 2004.PubMedCrossRefGoogle Scholar
  29. 29.
    Kanzaki, M., M. Yamato, H. Hatakeyama, C. Kohno, J. Yang, T. Umemoto, A. Kikuchi, T. Okano, and T. Onuki. Tissue engineered epithelial cell sheets for the creation of a bioartificial trachea. Tissue Eng. 12:1275–1283, 2006.PubMedCrossRefGoogle Scholar
  30. 30.
    Kim, J. H., J. Kim, W. H. Kong, and S. W. Seo. Factors affecting tissue culture and transplantation using omentum. ASAIO J. 56:349–355, 2010.PubMedGoogle Scholar
  31. 31.
    Kim, D. Y., J. Pyun, J. W. Choi, J. H. Kim, J. S. Lee, H. A. Shin, H. J. Kim, H. N. Lee, B. H. Min, H. E. Cha, and C. H. Kim. Tissue-engineered allograft tracheal cartilage using fibrin/hyaluronan composite gel and its in vivo implantation. Laryngoscope 120:30–38, 2010.PubMedCrossRefGoogle Scholar
  32. 32.
    Kojima, K., L. J. Bonassar, R. A. Ignotz, K. Syed, J. Cortiella, and C. A. Vacanti. Comparison of tracheal and nasal chondrocytes for tissue engineering of the trachea. Ann. Thorac. Surg. 76:1884–1888, 2003.PubMedCrossRefGoogle Scholar
  33. 33.
    Kojima, K., L. J. Bonassar, A. K. Roy, H. Mizuno, J. Cortiella, and C. A. Vacanti. A composite tissue-engineered trachea using sheep nasal chondrocyte and epithelial cells. FASEB J. 17:823–828, 2003.PubMedCrossRefGoogle Scholar
  34. 34.
    Kojima, K., L. J. Bonassar, A. K. Roy, C. A. Vacanti, and J. Cortiella. Autologous tissue-engineered trachea with sheep nasal chondrocytes. J. Thorac. Cardiovasc. Surg. 123:1177–1184, 2002.PubMedCrossRefGoogle Scholar
  35. 35.
    Kojima, K., R. A. Ignotz, T. Kushibiki, K. W. Tinsley, Y. Tabata, and C. A. Vacanti. Tissue-engineered trachea from sheep marrow stromal cells with transforming growth factor beta2 released from biodegradable microspheres in a nude rat recipient. J. Thorac. Cardiovasc. Surg. 128:147–153, 2004.PubMedCrossRefGoogle Scholar
  36. 36.
    Komura, M., H. Komura, Y. Kanamori, Y. Tanaka, K. Suzuki, M. Sugiyama, S. Nakahara, H. Kawashima, A. Hatanaka, K. Hoshi, Y. Ikada, Y. Tabata, and T. Iwanaka. An animal model study for tissue-engineered trachea fabricated from a biodegradable scaffold using chondrocytes to augment repair of tracheal stenosis. J. Pediatr. Surg. 43:2141–2146, 2008.PubMedCrossRefGoogle Scholar
  37. 37.
    Komura, M., H. Komura, Y. Tanaka, Y. Kanamori, M. Sugiyama, S. Nakahara, H. Kawashima, K. Suzuki, K. Hoshi, and T. Iwanaka. Human tracheal chondrocytes as a cell source for augmenting stenotic tracheal segments: the first feasibility study in an in vivo culture system. Pediatr. Surg. Int. 24:1117–1121, 2008.PubMedCrossRefGoogle Scholar
  38. 38.
    Kucera, K. A., A. E. Doss, S. S. Dunn, L. A. Clemson, and J. B. Zwischenberger. Tracheal replacements: part 1. ASAIO J. 53:497–505, 2007.PubMedCrossRefGoogle Scholar
  39. 39.
    Kunisaki, S. M., D. A. Freedman, and D. O. Fauza. Fetal tracheal reconstruction with cartilaginous grafts engineered from mesenchymal amniocytes. J. Pediatr. Surg. 41:675–682, 2006; (discussion 675–682).PubMedCrossRefGoogle Scholar
  40. 40.
    Lee, C. J., K. D. Moon, H. Choi, J. I. Woo, B. H. Min, and K. B. Lee. Tissue engineered tracheal prosthesis with acceleratedly cultured homologous chondrocytes as an alternative of tracheal reconstruction. J. Cardiovasc. Surg. (Torino) 43:275–279, 2002.Google Scholar
  41. 41.
    Liechty, K. W., T. C. MacKenzie, A. F. Shaaban, A. Radu, A. M. Moseley, R. Deans, D. R. Marshak, and A. W. Flake. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat. Med. 6:1282–1286, 2000.PubMedCrossRefGoogle Scholar
  42. 42.
    Lin, C. H., S. H. Hsu, C. E. Huang, W. T. Cheng, and J. M. Su. A scaffold-bioreactor system for a tissue-engineered trachea. Biomaterials 30:4117–4126, 2009.PubMedCrossRefGoogle Scholar
  43. 43.
    Lin, C. H., J. M. Su, and S. H. Hsu. Evaluation of type II collagen scaffolds reinforced by poly(epsilon-caprolactone) as tissue-engineered trachea. Tissue Eng. Part C Methods 14:69–77, 2008.PubMedCrossRefGoogle Scholar
  44. 44.
    Luo, X., G. Zhou, W. Liu, W. J. Zhang, L. Cen, L. Cui, and Y. Cao. In vitro precultivation alleviates post-implantation inflammation and enhances development of tissue-engineered tubular cartilage. Biomed. Mater. 4:025006, 2009.PubMedCrossRefGoogle Scholar
  45. 45.
    Lusk, R. P., D. R. Kang, and H. R. Muntz. Auricular cartilage grafts in laryngotracheal reconstruction. Ann. Otol. Rhinol. Laryngol. 102:247–254, 1993.PubMedGoogle Scholar
  46. 46.
    Macchiarini, M. P. Airway transplantation: a debate worth having? Transplantation 85:1075–1080, 2008.PubMedCrossRefGoogle Scholar
  47. 47.
    Macchiarini, P., P. Jungebluth, T. Go, M. A. Asnaghi, L. E. Rees, T. A. Cogan, A. Dodson, J. Martorell, S. Bellini, P. P. Parnigotto, S. C. Dickinson, A. P. Hollander, S. Mantero, M. T. Conconi, and M. A. Birchall. Clinical transplantation of a tissue-engineered airway. Lancet 372:2023–2030, 2008.PubMedCrossRefGoogle Scholar
  48. 48.
    Macchiarini, P., T. Walles, C. Biancosino, and H. Mertsching. First human transplantation of a bioengineered airway tissue. J. Thorac. Cardiovasc. Surg. 128:638–641, 2004.PubMedCrossRefGoogle Scholar
  49. 49.
    Matloub, H. S., and P. Yu. Engineering a composite neotrachea in a rat model. Plast. Reconstr. Surg. 117:123–128, 2006.PubMedCrossRefGoogle Scholar
  50. 50.
    Mertsching, H., T. Walles, M. Hofmann, J. Schanz, and W. H. Knapp. Engineering of a vascularized scaffold for artificial tissue and organ generation. Biomaterials 26:6610–6617, 2005.PubMedCrossRefGoogle Scholar
  51. 51.
    Mironov, V., R. P. Visconti, V. Kasyanov, G. Forgacs, C. J. Drake, and R. R. Markwald. Organ printing: tissue spheroids as building blocks. Biomaterials 30:2164–2174, 2009.PubMedCrossRefGoogle Scholar
  52. 52.
    Moroni, L., M. Curti, M. Welti, S. Korom, W. Weder, J. R. de Wijn, and C. A. van Blitterswijk. Anatomical 3D fiber-deposited scaffolds for tissue engineering: designing a neotrachea. Tissue Eng. 13:2483–2493, 2007.PubMedCrossRefGoogle Scholar
  53. 53.
    Nakamura, T., T. Sato, M. Araki, S. Ichihara, A. Nakada, M. Yoshitani, S. Itoi, M. Yamashita, S. Kanemaru, K. Omori, Y. Hori, K. Endo, Y. Inada, and K. Hayakawa. In situ tissue engineering for tracheal reconstruction using a luminar remodeling type of artificial trachea. J. Thorac. Cardiovasc. Surg. 138:811–819, 2009.PubMedCrossRefGoogle Scholar
  54. 54.
    Nakamura, T., M. Teramachi, T. Sekine, R. Kawanami, S. Fukuda, M. Yoshitani, T. Toba, H. Ueda, Y. Hori, M. Inoue, K. Shigeno, T. N. Taka, Y. Liu, N. Tamura, and Y. Shimizu. Artificial trachea and long term follow-up in carinal reconstruction in dogs. Int. J. Artif. Organs 23:718–724, 2000.PubMedGoogle Scholar
  55. 55.
    Neville, W. E., J. P. Bolanowski, and G. G. Kotia. Clinical experience with the silicone tracheal prosthesis. J. Thorac. Cardiovasc. Surg. 99:604–612, 1990; (discussion 612–613).PubMedGoogle Scholar
  56. 56.
    Ni, Y., X. Zhao, L. Zhou, Z. Shao, W. Yan, X. Chen, Z. Cao, Z. Xue, and J. J. Jiang. Radiologic and histologic characterization of silk fibroin as scaffold coating for rabbit tracheal defect repair. Otolaryngol. Head Neck Surg. 139:256–261, 2008.PubMedCrossRefGoogle Scholar
  57. 57.
    Nomoto, Y., K. Kobayashi, Y. Tada, I. Wada, T. Nakamura, and K. Omori. Effect of fibroblasts on epithelial regeneration on the surface of a bioengineered trachea. Ann. Otol. Rhinol. Laryngol. 117:59–64, 2008.PubMedGoogle Scholar
  58. 58.
    Nomoto, Y., T. Suzuki, Y. Tada, K. Kobayashi, M. Miyake, A. Hazama, I. Wada, S. Kanemaru, T. Nakamura, and K. Omori. Tissue engineering for regeneration of the tracheal epithelium. Ann. Otol. Rhinol. Laryngol. 115:501–506, 2006.PubMedGoogle Scholar
  59. 59.
    Ohara, K., K. Nakamura, and E. Ohta. Chest wall deformities and thoracic scoliosis after costal cartilage graft harvesting. Plast. Reconstr. Surg. 99:1030–1036, 1997.PubMedCrossRefGoogle Scholar
  60. 60.
    Okumura, N., M. Teramachi, Y. Takimoto, T. Nakamura, Y. Ikada, and Y. Shimizu. Experimental reconstruction of the intrathoracic trachea using a new prosthesis made from collagen grafted mesh. ASAIO J. 40:M834–M839, 1994.PubMedCrossRefGoogle Scholar
  61. 61.
    Omori, K., T. Nakamura, S. Kanemaru, R. Asato, M. Yamashita, S. Tanaka, A. Magrufov, J. Ito, and Y. Shimizu. Regenerative medicine of the trachea: the first human case. Ann. Otol. Rhinol. Laryngol. 114:429–433, 2005.PubMedGoogle Scholar
  62. 62.
    Omori, K., T. Nakamura, S. Kanemaru, H. Kojima, A. Magrufov, Y. Hiratsuka, and Y. Shimizu. Cricoid regeneration using in situ tissue engineering in canine larynx for the treatment of subglottic stenosis. Ann. Otol. Rhinol. Laryngol. 113:623–627, 2004.PubMedGoogle Scholar
  63. 63.
    Omori, K., T. Nakamura, S. Kanemaru, A. Magrufov, M. Yamashita, and Y. Shimizu. In situ tissue engineering of the cricoid and trachea in a canine model. Ann. Otol. Rhinol. Laryngol. 117:609–613, 2008.PubMedGoogle Scholar
  64. 64.
    Omori, K., Y. Tada, T. Suzuki, Y. Nomoto, T. Matsuzuka, K. Kobayashi, T. Nakamura, S. Kanemaru, M. Yamashita, and R. Asato. Clinical application of in situ tissue engineering using a scaffolding technique for reconstruction of the larynx and trachea. Ann. Otol. Rhinol. Laryngol. 117:673–678, 2008.PubMedGoogle Scholar
  65. 65.
    Osada, H., S. Takeuchi, K. Kojima, and N. Yamate. The first step of experimental study on hybrid trachea: use of cultured fibroblasts with artificial matrix. J. Cardiovasc. Surg. (Torino) 35:165–168, 1994.Google Scholar
  66. 66.
    Pfenninger, C., I. Leinhase, M. Endres, N. Rotter, A. Loch, J. Ringe, and M. Sittinger. Tracheal remodeling: comparison of different composite cultures consisting of human respiratory epithelial cells and human chondrocytes. In Vitro Cell Dev. Biol. Anim. 43:28–36, 2007.PubMedCrossRefGoogle Scholar
  67. 67.
    Pham, Q. P., U. Sharma, and A. G. Mikos. Electrospinning of polymeric nanofibers for tissue engineering applications: a review. Tissue Eng. 12:1197–1211, 2006.PubMedCrossRefGoogle Scholar
  68. 68.
    Remlinger, N. T., C. A. Czajka, M. E. Juhas, D. A. Vorp, D. B. Stolz, S. F. Badylak, S. Gilbert, and T. W. Gilbert. Hydrated xenogeneic decellularized tracheal matrix as a scaffold for tracheal reconstruction. Biomaterials 31:3520–3526, 2010.PubMedCrossRefGoogle Scholar
  69. 69.
    Risbud, M., M. Endres, J. Ringe, R. Bhonde, and M. Sittinger. Biocompatible hydrogel supports the growth of respiratory epithelial cells: possibilities in tracheal tissue engineering. J. Biomed. Mater. Res. 56:120–127, 2001.PubMedCrossRefGoogle Scholar
  70. 70.
    Roomans, G. M. Tissue engineering and the use of stem/progenitor cells for airway epithelium repair. Eur. Cell Mater. 19:284–299, 2010.PubMedGoogle Scholar
  71. 71.
    Ruszymah, B. H., K. Chua, M. A. Latif, F. N. Hussein, and A. B. Saim. Formation of in vivo tissue engineered human hyaline cartilage in the shape of a trachea with internal support. Int. J. Pediatr. Otorhinolaryngol. 69:1489–1495, 2005.PubMedCrossRefGoogle Scholar
  72. 72.
    Sakata, J., C. A. Vacanti, B. Schloo, G. B. Healy, R. Langer, and J. P. Vacanti. Tracheal composites tissue engineered from chondrocytes, tracheal epithelial cells, and synthetic degradable scaffolding. Transpl. Proc. 26:3309–3310, 1994.Google Scholar
  73. 73.
    Sato, T., M. Araki, N. Nakajima, K. Omori, and T. Nakamura. Biodegradable polymer coating promotes the epithelization of tissue-engineered airway prostheses. J. Thorac. Cardiovasc. Surg. 139:26–31, 2010.PubMedCrossRefGoogle Scholar
  74. 74.
    Sato, T., and T. Nakamura. Tissue-engineered airway replacement. Lancet 372:2003–2004, 2008.PubMedCrossRefGoogle Scholar
  75. 75.
    Schanz, J., J. Pusch, J. Hansmann, and H. Walles. Vascularised human tissue models: a new approach for the refinement of biomedical research. J. Biotechnol. 148(1):56–63, 2010.PubMedCrossRefGoogle Scholar
  76. 76.
    Seguin, A., D. Radu, M. Holder-Espinasse, P. Bruneval, A. Fialaire-Legendre, M. Duterque-Coquillaud, A. Carpentier, and E. Martinod. Tracheal replacement with cryopreserved, decellularized, or glutaraldehyde-treated aortic allografts. Ann. Thorac. Surg. 87:861–867, 2009.PubMedCrossRefGoogle Scholar
  77. 77.
    Sekine, T., T. Nakamura, H. Ueda, K. Matsumoto, Y. Yamamoto, Y. Takimoto, T. Kiyotani, and Y. Shimizu. Replacement of the tracheobronchial bifurcation by a newly developed Y-shaped artificial trachea. ASAIO J. 45:131–134, 1999.PubMedCrossRefGoogle Scholar
  78. 78.
    Shinoka, T., D. Shum-Tim, P. X. Ma, R. E. Tanel, N. Isogai, R. Langer, J. P. Vacanti, and J. E. Mayer, Jr. Creation of viable pulmonary artery autografts through tissue engineering. J. Thorac. Cardiovasc. Surg. 115:536–545, 1998; (discussion 545–546).PubMedCrossRefGoogle Scholar
  79. 79.
    Shoichet, M. S. Polymer scaffolds for biomaterials applications. Macromolecules 43:581–591, 2009.CrossRefGoogle Scholar
  80. 80.
    Suzuki, T., K. Kobayashi, Y. Tada, Y. Suzuki, I. Wada, T. Nakamura, and K. Omori. Regeneration of the trachea using a bioengineered scaffold with adipose-derived stem cells. Ann. Otol. Rhinol. Laryngol. 117:453–463, 2008.PubMedGoogle Scholar
  81. 81.
    Tada, Y., T. Suzuki, T. Takezawa, Y. Nomoto, K. Kobayashi, T. Nakamura, and K. Omori. Regeneration of tracheal epithelium utilizing a novel bipotential collagen scaffold. Ann. Otol. Rhinol. Laryngol. 117:359–365, 2008.PubMedGoogle Scholar
  82. 82.
    Tan, Q., A. M. El-Badry, C. Contaldo, R. Steiner, S. Hillinger, M. Welti, M. Hilbe, D. R. Spahn, R. Jaussi, G. Higuera, C. A. van Blitterswijk, Q. Luo, and W. Weder. The effect of perfluorocarbon-based artificial oxygen carriers on tissue-engineered trachea. Tissue Eng. A 15:2471–2480, 2009.CrossRefGoogle Scholar
  83. 83.
    Tan, Q., S. Hillinger, C. A. van Blitterswijk, and W. Weder. Intra-scaffold continuous medium flow combines chondrocyte seeding and culture systems for tissue engineered trachea construction. Interact. Cardiovasc. Thorac. Surg. 8:27–30, 2009.PubMedCrossRefGoogle Scholar
  84. 84.
    Tan, Q., R. Steiner, S. P. Hoerstrup, and W. Weder. Tissue-engineered trachea: history, problems and the future. Eur. J. Cardiothorac. Surg. 30:782–786, 2006.PubMedCrossRefGoogle Scholar
  85. 85.
    Tan, Q., R. Steiner, L. Yang, M. Welti, P. Neuenschwander, S. Hillinger, and W. Weder. Accelerated angiogenesis by continuous medium flow with vascular endothelial growth factor inside tissue-engineered trachea. Eur. J. Cardiothorac. Surg. 31:806–811, 2007.PubMedCrossRefGoogle Scholar
  86. 86.
    Tani, G., N. Usui, M. Kamiyama, T. Oue, and M. Fukuzawa. In vitro construction of scaffold-free cylindrical cartilage using cell sheet-based tissue engineering. Pediatr. Surg. Int. 26:179–185, 2010.PubMedCrossRefGoogle Scholar
  87. 87.
    ten Hallers, E. J., G. Rakhorst, H. A. Marres, J. A. Jansen, T. G. van Kooten, H. K. Schutte, J. P. van Loon, E. B. van der Houwen, and G. J. Verkerke. Animal models for tracheal research. Biomaterials 25:1533–1543, 2004.PubMedCrossRefGoogle Scholar
  88. 88.
    Teramachi, M., T. Nakamura, Y. Yamamoto, T. Kiyotani, Y. Takimoto, and Y. Shimizu. Porous-type tracheal prosthesis sealed with collagen sponge. Ann. Thorac. Surg. 64:965–969, 1997.PubMedCrossRefGoogle Scholar
  89. 89.
    Thomson, H. G., T. Y. Kim, and S. H. Ein. Residual problems in chest donor sites after microtia reconstruction: a long-term study. Plast. Reconstr. Surg. 95:961–968, 1995.PubMedCrossRefGoogle Scholar
  90. 90.
    Toomes, H., G. Mickisch, and I. Vogt-Moykopf. Experiences with prosthetic reconstruction of the trachea and bifurcation. Thorax 40:32–37, 1985.PubMedCrossRefGoogle Scholar
  91. 91.
    Tsukada, H., S. Matsuda, H. Inoue, Y. Ikada, and H. Osada. Comparison of bioabsorbable materials for use in artificial tracheal grafts. Interact. Cardiovasc. Thorac. Surg. 8:225–229, 2009.PubMedCrossRefGoogle Scholar
  92. 92.
    Vacanti, C. A., K. T. Paige, W. S. Kim, J. Sakata, J. Upton, and J. P. Vacanti. Experimental tracheal replacement using tissue-engineered cartilage. J. Pediatr. Surg. 29:201–204, 1994; (discussion 204–205).PubMedCrossRefGoogle Scholar
  93. 93.
    von der Mark, K., V. Gauss, H. von der Mark, and P. Muller. Relationship between cell shape and type of collagen synthesised as chondrocytes lose their cartilage phenotype in culture. Nature 267:531–532, 1977.CrossRefGoogle Scholar
  94. 94.
    Walles, T., B. Giere, M. Hofmann, J. Schanz, F. Hofmann, H. Mertsching, and P. Macchiarini. Experimental generation of a tissue-engineered functional and vascularized trachea. J. Thorac. Cardiovasc. Surg. 128:900–906, 2004.PubMedGoogle Scholar
  95. 95.
    Walles, T., B. Giere, P. Macchiarini, and H. Mertsching. Expansion of chondrocytes in a three-dimensional matrix for tracheal tissue engineering. Ann. Thorac. Surg. 78:444–448, 2004; (discussion 448–449).PubMedCrossRefGoogle Scholar
  96. 96.
    Weidenbecher, M., J. H. Henderson, H. M. Tucker, J. Z. Baskin, A. Awadallah, and J. E. Dennis. Hyaluronan-based scaffolds to tissue-engineer cartilage implants for laryngotracheal reconstruction. Laryngoscope 117:1745–1749, 2007.PubMedCrossRefGoogle Scholar
  97. 97.
    Weidenbecher, M., H. M. Tucker, A. Awadallah, and J. E. Dennis. Fabrication of a neotrachea using engineered cartilage. Laryngoscope 118:593–598, 2008.PubMedCrossRefGoogle Scholar
  98. 98.
    Weidenbecher, M., H. M. Tucker, D. A. Gilpin, and J. E. Dennis. Tissue-engineered trachea for airway reconstruction. Laryngoscope 119:2118–2123, 2009.PubMedCrossRefGoogle Scholar
  99. 99.
    Windpipe Transplant Success in UK Child. BBC News. March 19, 2010. URL:
  100. 100.
    Wu, W., X. Cheng, Y. Zhao, F. Chen, X. Feng, and T. Mao. Tissue engineering of trachea-like cartilage grafts by using chondrocyte macroaggregate: experimental study in rabbits. Artif. Organs 31:826–834, 2007.PubMedCrossRefGoogle Scholar
  101. 101.
    Wu, W., X. Feng, T. Mao, H. W. Ouyang, G. Zhao, and F. Chen. Engineering of human tracheal tissue with collagen-enforced poly-lactic-glycolic acid non-woven mesh: a preliminary study in nude mice. Br. J. Oral Maxillofac. Surg. 45:272–278, 2007.PubMedCrossRefGoogle Scholar
  102. 102.
    Wu, W., Y. Liu, and Y. Zhao. Clinical transplantation of a tissue-engineered airway. Lancet 373:717, 2009; (author reply 718–719).PubMedCrossRefGoogle Scholar
  103. 103.
    Yamamoto, Y., T. Okamoto, M. Goto, H. Yokomise, M. Yamamoto, and Y. Tabata. Experimental study of bone morphogenetic proteins-2 slow release from an artificial trachea made of biodegradable materials: evaluation of stenting time. ASAIO J. 49:533–536, 2003.PubMedCrossRefGoogle Scholar
  104. 104.
    Yamashita, M., S. Kanemaru, S. Hirano, A. Magrufov, H. Tamaki, Y. Tamura, M. Kishimoto, K. Omori, T. Nakamura, and J. Ito. Tracheal regeneration after partial resection: a tissue engineering approach. Laryngoscope 117:497–502, 2007.PubMedCrossRefGoogle Scholar
  105. 105.
    Yanagi, M., A. Kishida, T. Shimotakahara, H. Matsumoto, H. Nishijima, M. Akashi, and T. Aikou. Experimental study of bioactive polyurethane sponge as an artificial trachea. ASAIO J. 40:M412–M418, 1994.PubMedCrossRefGoogle Scholar
  106. 106.
    Yang, L., S. Korom, M. Welti, S. P. Hoerstrup, G. Zund, F. J. Jung, P. Neuenschwander, and W. Weder. Tissue engineered cartilage generated from human trachea using DegraPol scaffold. Eur. J. Cardiothorac. Surg. 24:201–207, 2003.PubMedCrossRefGoogle Scholar
  107. 107.
    Zani, B. G., K. Kojima, C. A. Vacanti, and E. R. Edelman. Tissue-engineered endothelial and epithelial implants differentially and synergistically regulate airway repair. Proc. Natl. Acad. Sci. USA 105:7046–7051, 2008.PubMedCrossRefGoogle Scholar
  108. 108.
    Zhang, J. R., F. L. Chen, W. Wu, J. H. Wei, X. H. Feng, and T. Q. Mao. Constructing tissue engineered trachea-like cartilage graft in vitro by using bone marrow stromal cells sheet and PLGA internal support: experimental study in bioreactor. Zhonghua Zheng Xing Wai Ke Za Zhi 25:124–128, 2009.PubMedGoogle Scholar

Copyright information

© Biomedical Engineering Society 2011

Authors and Affiliations

  • Lindsey M. Ott
    • 1
  • Robert A. Weatherly
    • 2
    • 3
  • Michael S. Detamore
    • 1
    • 4
  1. 1.Bioengineering ProgramUniversity of KansasLawrenceUSA
  2. 2.Section of OtolaryngologyChildren’s Mercy HospitalKansas CityUSA
  3. 3.Department of PediatricsThe University of Missouri, Kansas City School of MedicineKansas CityUSA
  4. 4.Department of Chemical and Petroleum EngineeringUniversity of KansasLawrenceUSA

Personalised recommendations