Skip to main content

Advertisement

Log in

Applications of tissue engineering in modern laryngology


  • Main Topic
  • Published:
European Surgery Aims and scope Submit manuscript

Summary

Background

Tissue Engineering is a multidimensional approach that aims to produce a structure similar to target tissue. Main targets in laryngeal tissue engineering (TE) are chronic vocal fold scars and vocal fold atrophy which occurs in elderly patients. The main obstacle for restoration is the highly complex architecture of the human vocal fold. Deterioration of its micro-architecture leads to altered vibration characteristics that have deleterious effects on voice quality, causing hoarseness (dysphonia). The aim of this study is to give an actual clinical and experimental overview of this field as well as to further elucidate promising new findings and trends.

Methods

We performed a PubMed survey on articles relevant to this field.

Results

Fifty relevant articles were included that reflect the latest advances with growth factors, cell therapy and scaffold engineering, as well the first applications in humans. Cell therapy, using somatic or stem cells, remains highly promising; however, there is a lack of applications in humans due to safety concerns. Different types of scaffolds have been investigated and atelocollagen sheets were already implanted in human vocal folds. Many trials used a combined approach of cell therapy, scaffolds, and different growth factors.

Conclusions

Experiments and trials in laryngeal tissue engineering have emerged over the last decades and clinical use is near. Within this review, we discuss the latest developments to encourage further research on this fascinating topic. Similar to other fields, a close cooperation between different professions such as physicians, bioengineers, as well as industrial partners is required to succeed in laryngeal TE.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ling C, Yamashita M, Waselchuk EA, Raasch JL, Bless DM, Welham NV. Alteration in cellular morphology, density and distribution in rat vocal fold mucosa following injury. Wound Repair Regen. 2010;18:89–97.

    Article  PubMed  Google Scholar 

  2. Ruben RJ. Redefining the survival of the fittest: communication disorders in the 21st century. Laryngoscope. 2000;110:241–5.

    Article  PubMed  CAS  Google Scholar 

  3. Hirano M. Morphological structure of the vocal cord as a vibrator and its variations. Folia Phoniatr (Basel). 1974;26:89–94.

    Article  CAS  Google Scholar 

  4. Gray SD, Titze IR, Alipour F, Hammond TH. Biomechanical and histologic observations of vocal fold fibrous proteins. Ann Otol Rhinol Laryngol. 2000;109:77–85.

    PubMed  CAS  Google Scholar 

  5. Hansen JK, Thibeault SL. Current understanding and review of the literature: vocal fold scarring. J Voice. 2006;20:110–20.

    Article  PubMed  Google Scholar 

  6. Suehiro A, Hirano S, Kishimoto Y, Rousseau B, Nakamura T, Ito J. Treatment of acute vocal fold scar with local injection of basic fibroblast growth factor: a canine study. Acta Otolaryngol. 2010;130:844–50.

    Article  PubMed  CAS  Google Scholar 

  7. Suehiro A, Hirano S, Kishimoto Y, Tateya I, Rousseau B, Ito J. Effects of basic fibroblast growth factor on rat vocal fold fibroblasts. Ann Otol Rhinol Laryngol. 2010;119:690–6.

    PubMed  Google Scholar 

  8. Kishimoto Y, Hirano S, Suehiro A, et al. Effect of exogenous hepatocyte growth factor on vocal fold fibroblasts. Ann Otol Rhinol Laryngol. 2009;118:606–11.

    PubMed  Google Scholar 

  9. Kishimoto Y, Hirano S, Kitani Y, et al. Chronic vocal fold scar restoration with hepatocyte growth factor hydrogel. Laryngoscope. 2010;120:108–13.

    Article  PubMed  Google Scholar 

  10. Ohno T, French LC, Hirano S, Ossoff RH, Rousseau B. Effect of hepatocyte growth factor on gene expression of extracellular matrix during wound healing of the injured rat vocal fold. Ann Otol Rhinol Laryngol. 2008;117:696–702.

    PubMed  Google Scholar 

  11. Hirano S, Kishimoto Y, Suehiro A, Kanemaru S, Ito J. Regeneration of aged vocal fold: first human case treated with fibroblast growth factor. Laryngoscope. 2008;118:2254–9.

    Article  PubMed  Google Scholar 

  12. Branski RC, Barbieri SS, Weksler BB, et al. Effects of transforming growth factor-beta1 on human vocal fold fibroblasts. Ann Otol Rhinol Laryngol. 2009;118:218–26.

    PubMed  Google Scholar 

  13. Hirano S, Nagai H, Tateya I, Tateya T, Ford CN, Bless DM. Regeneration of aged vocal folds with basic fibroblast growth factor in a rat model: a preliminary report. Ann Otol Rhinol Laryngol. 2005;114:304–8.

    PubMed  Google Scholar 

  14. Hirano S. Current treatment of vocal fold scarring. Curr Opin Otolaryngol Head Neck Surg. 2005;13:143–7.

    Article  PubMed  Google Scholar 

  15. Rousseau B, Sohn J, Montequin DW, Tateya I, Bless DM. Functional outcomes of reduced hyaluronan in acute vocal fold scar. Ann Otol Rhinol Laryngol. 2004;113:767–76.

    PubMed  Google Scholar 

  16. Matsumoto K, Nakamura T. Hepatocyte growth factor (HGF) as a tissue organizer for organogenesis and regeneration. Biochem Biophys Res Commun. 1997;239:639–44.

    Article  PubMed  CAS  Google Scholar 

  17. Hirano S, Bless D, Heisey D, Ford C. Roles of hepatocyte growth factor and transforming growth factor beta1 in production of extracellular matrix by canine vocal fold fibroblasts. Laryngoscope. 2003;113:144–8.

    Article  PubMed  CAS  Google Scholar 

  18. Sheen-Chen SM, Liu YW, Eng HL, Chou FF. Serum levels of hepatocyte growth factor in patients with breast cancer. Cancer Epidemiol Biomarkers Prev. 2005;14:715–7.

    Article  PubMed  CAS  Google Scholar 

  19. Gugatschka M, Kojima T, Ohno S, Kanemaru S, Hirano S. Recruitment patterns of side population cells during wound healing in rat vocal folds. Laryngoscope. 2011;121:1662–7.

    Article  PubMed  Google Scholar 

  20. Chhetri DK, Berke GS. Injection of cultured autologous fibroblasts for human vocal fold scars. Laryngoscope. 2011;121:785–92.

    Article  PubMed  Google Scholar 

  21. Kanemaru S, Nakamura T, Omori K, et al. Regeneration of the vocal fold using autologous mesenchymal stem cells. Ann Otol Rhinol Laryngol. 2003;112:915–20.

    PubMed  Google Scholar 

  22. Xu W, Hu R, Fan E, Han D. Adipose-derived mesenchymal stem cells in collagen-hyaluronic acid gel composite scaffolds for vocal fold regeneration. Ann Otol Rhinol Laryngol. 2011;120:123–30.

    PubMed  Google Scholar 

  23. Kumai Y, Kobler JB, Herrera VL, Zeitels SM. Perspectives on adipose-derived stem/stromal cells as potential treatment for scarred vocal folds: opportunity and challenges. Curr Stem Cell Res Ther. 2010;5:175–81.

    Article  PubMed  CAS  Google Scholar 

  24. Park H, Karajanagi S, Wolak K, et al. Three-dimensional hydrogel model using adipose-derived stem cells for vocal fold augmentation. Tissue Eng Part A. 2010;16:535–43.

    Article  PubMed  CAS  Google Scholar 

  25. Zhang F, Sprecher AJ, Wei C, Jiang JJ. Implantation of gelatin sponge combined with injection of autologous fat for sulcus vocalis. Otolaryngol Head Neck Surg. 2010;143:198–203.

    Article  PubMed  Google Scholar 

  26. Luo Y, Kobler JB, Heaton JT, Jia X, Zeitels SM, Langer R. Injectable hyaluronic acid-dextran hydrogels and effects of implantation in ferret vocal fold. J Biomed Mater Res B Appl Biomater. 2010;93:386–93.

    PubMed  Google Scholar 

  27. Long JL. Tissue engineering for treatment of vocal fold scar. Curr Opin Otolaryngol Head Neck Surg. 2010;40(5):521–5.

    Article  Google Scholar 

  28. Prestwich GD, Shu XZ, Liu Y, et al. Injectable synthetic extracellular matrices for tissue engineering and repair. Adv Exp Med Biol. 2006;585:125–33.

    Article  PubMed  CAS  Google Scholar 

  29. Prestwich GD. Hyaluronic acid-based clinical biomaterials derived for cell and molecule delivery in regenerative medicine. J Control Release. 2011;155:193–9.

    Article  PubMed  CAS  Google Scholar 

  30. Bartlett RS, Thibeault SL, Prestwich GD. Therapeutic potential of gel-based injectables for vocal fold regeneration. Biomed Mater. 2012;7:024103–6041/7/2/024103. Epub 2012 Mar 29.

    Google Scholar 

  31. Kishimoto Y, Welham NV, Hirano S. Implantation of atelocollagen sheet for vocal fold scar. Curr Opin Otolaryngol Head Neck Surg. 2010;18(6):507–11.

    Article  PubMed  Google Scholar 

  32. Ohno S, Hirano S, Tateya I, et al. Atelocollagen sponge as a stem cell implantation scaffold for the treatment of scarred vocal folds. Ann Otol Rhinol Laryngol. 2009;118:805–10.

    PubMed  Google Scholar 

  33. Teramachi M, Nakamura T, Yamamoto Y, Kiyotani T, Takimoto Y, Shimizu Y. Porous-type tracheal prosthesis sealed with collagen sponge. Ann Thorac Surg. 1997;64:965–9.

    Article  PubMed  CAS  Google Scholar 

  34. Nakamura T, Teramachi M, Sekine T, et al. Artificial trachea and long term follow-up in carinal reconstruction in dogs. Int J Artif Organs. 2000;23:718–24.

    PubMed  CAS  Google Scholar 

  35. Omori K, Nakamura T, Kanemaru S, et al. Cricoid regeneration using in situ tissue engineering in canine larynx for the treatment of subglottic stenosis. Ann Otol Rhinol Laryngol. 2004;113:623–7.

    PubMed  Google Scholar 

  36. Omori K, Tada Y, Suzuki T, et al. Clinical application of in situ tissue engineering using a scaffolding technique for reconstruction of the larynx and trachea. Ann Otol Rhinol Laryngol. 2008;117:673–8.

    PubMed  Google Scholar 

  37. Okano W, Nomoto Y, Wada I, et al. Bioengineered trachea with fibroblasts in a rabbit model. Ann Otol Rhinol Laryngol. 2009;118:796–804.

    PubMed  Google Scholar 

  38. Nomoto Y, Kobayashi K, Tada Y, Wada I, Nakamura T, Omori K. Effect of fibroblasts on epithelial regeneration on the surface of a bioengineered trachea. Ann Otol Rhinol Laryngol. 2008;117:59–64.

    PubMed  Google Scholar 

  39. Nomoto Y, Okano W, Imaizumi M, Tani A, Nomoto M, Omori K. Bioengineered prosthesis with allogenic heterotopic fibroblasts for cricoid regeneration. Laryngoscope. 2012;122:805–9.

    Article  PubMed  Google Scholar 

  40. Igai H, Chang SS, Gotoh M, et al. Widespread and early tracheal cartilage regeneration by synchronous slow release of b-FGF and BMP-2. ASAIO J. 2009;55:266–70.

    Article  PubMed  CAS  Google Scholar 

  41. Yamashita M, Kanemaru S, Hirano S, et al. Glottal reconstruction with a tissue engineering technique using polypropylene mesh: a canine experiment. Ann Otol Rhinol Laryngol. 2010;119:110–7.

    PubMed  Google Scholar 

  42. Hou N, Cui P, Luo J, Ma R, Zhu L. Tissue-engineered larynx using perfusion-decellularized technique and mesenchymal stem cells in a rabbit model. Acta Otolaryngol. 2011;131:645–52.

    Article  PubMed  CAS  Google Scholar 

  43. Macchiarini P, Jungebluth P, Go T, et al. Clinical transplantation of a tissue-engineered airway. Lancet. 2008;372:2023–30.

    Article  PubMed  Google Scholar 

  44. Laurance J. British boy receives trachea transplant built with his own stem cells. BMJ. 2010;340:c1633.

    Article  PubMed  Google Scholar 

  45. Baiguera S, Jungebluth P, Burns A, et al. Tissue engineered human tracheas for in vivo implantation. Biomaterials. 2010;31:8931–8.

    Article  PubMed  CAS  Google Scholar 

  46. Jungebluth P, Alici E, Baiguera S, et al. Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study. Lancet. 2011;378(9808):1997–2004.

    Article  PubMed  CAS  Google Scholar 

  47. Fuchs JR, Terada S, Ochoa ER, Vacanti JP, Fauza DO. Fetal tissue engineering: in utero tracheal augmentation in an ovine model. J Pediatr Surg. 2002;37:1000–6; discussion 1000–6.

    Article  PubMed  Google Scholar 

  48. Kunisaki SM, Freedman DA, Fauza DO. Fetal tracheal reconstruction with cartilaginous grafts engineered from mesenchymal amniocytes. J Pediatr Surg. 2006;41:675–82; discussion 675–82.

    Article  PubMed  Google Scholar 

  49. Elliott MJ, De Coppi P, Speggiorin S, et al. Stem-cell-based, tissue engineered tracheal replacement in a child: a 2-year follow-up study. Lancet. 2012;380:994–1000.

    Article  PubMed  Google Scholar 

  50. Baiguera S, Gonfiotti A, Jaus M, et al. Development of bioengineered human larynx. Biomaterials. 2011;32:4433–42.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest


The authors declare that there is no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Gugatschka MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gugatschka, M., Graupp, M. & Friedrich, G. Applications of tissue engineering in modern laryngology
. Eur Surg 45, 136–141 (2013). https://doi.org/10.1007/s10353-013-0214-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10353-013-0214-z

Keywords

Navigation