Section 4 Plastic and Reconstructive Problems

Tissue Engineering in Otorhinolaryngology

embryonic stem cells, and to clarify long-term safety profiles of these promising biomaterials.

Despite these promising studies, there are many issues that still need to be clarified. Most important of all, the ideal dose and duration of the treatment must be determined and special attention must be given to the definition of potential risks that may arise with the use of these factors, such as cholesteatoma formation.

Conflict of Interest

The authors declares no disclosures.

Scaffolds

Acknowledgments

A range of different materials have been studied in the reconstruction of the tympanic membrane, namely the com- ponents of extracellular matrix and calcium alginate. The components of extracellular matrix are derived from natural sources (acellular dermis and dura mater) and used as templates for tissue reconstruction based on their ultrastructure, particularly the presence of functional proteins such as collagen and proteoglycans. 32 The extra- cellular matrix extracted from porcine dermis and dura mater and submitted to decellularization processes were used in a study by Deng et al. 39 In this work, fibrob- lasts isolated from guinea pig’s tympanic membrane were added to the described biomaterial and then placed on a chronically perforated tympanic membrane using the tympanoplasty underlay technique. Subsequent microscopic analysis revealed progressive reconstruction of a char- acteristic 3-layered tympanic membrane, associated with improvement of hearing thresholds in the auditory evoked potential examination. On the other hand, alginate is a natural polymer orig- inated from seaweed, which has been used as a scaffold in tissue engineering due to its positive effects on cellu- lar proliferation. 40 When cross-linked with calcium salts, its properties are significantly enhanced, particularly in what concerns handling and resilience, 40 as observed in a study performed by Weber et al. 41 comparing it with the paper patch technique used in myringoplasties on chinchilla with induced chronic tympanic perforations. At the end of the study, perforated tympanic membrane treated with calcium alginate had a higher occlusion rate when compared to con- trols, while auditory potentials confirmed the absence of toxic effects. Despite these promising results, these materials must be extensively evaluated concerning the potential risks of its use compared with autologous materials currently used in common practice, with very satisfactory results but with considerable morbidity. With the increased knowledge and establishment of the con- cepts of regenerative medicine, as well as the constant development of new biomaterials, the paradigm of medicine will soon change. In the future, the doctor, and particu- larly the otolaryngologist will assume a role in the process that includes not only the diagnosis but in the restoration of compromised biological functions, being part of a multidis- ciplinary team which will soon include engineers, biologists and other related professionals. Again, further studies are clearly needed to regulate inherent ethical issues, particularly regarding the use of Conclusion

The 3B’s Research Group (Biomaterials, Biodegradables and Biomimetics).

References

1. Saxena A. Tissue engineering. J Indian Assoc Pediatr Surg. 2005;10:14--9. 2. Sivayoham E, Saunders R, Derby B, Woolford T. Current concepts and advances in application of tissue engineering in otorhi- nolaryngology and head and neck surgery. J Laryngol Otol. 2013;127:114--20. 3. Hirano S. Tissue engineering for voice disorder. JMAJ. 2011;139:827--30. 4. Thomson J, Itskovitz-Eldor J, Shapiro S, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282:1145--7. 5. Gugatschka M, Ohno S, Saxena A, Hirano S. Regenerative medicine of the larynx. Where are we today? A review. J Voice. 2012;26, 670.e7--670.e13. 6. Chen X, Thibeault S. Biocompatibility of a synthetic extracellu- lar matrix on immortalized vocal fold fibroblasts in 3D culture. Acta Biomater. 2010;6:2940--8. 7. Dailey S, Gunderson M, Chan R, Torrealba J, Kimura M, Welham NV. Local vascularized flaps for augmentation of Reinke’s space. Laryngoscope. 2011;121:37--60. 8. Johnson B, Fox R, Chen X, Thibeault S. Tissue regeneration of the vocal fold using bone marrow mesenchymal stem cells and synthetic extracellular matrix injections in rats. Laryngoscope. 2010;120:537--45. 9. Thibeault S, Klemuk S, Chen X, Quinchia Johnson BH. In vivo engineering of the vocal fold ECM with injectable HA hydrogels- late effects on tissue repair and biomechanics in a rabbit model. J Voice. 2011;25:249--53. 10. Kishimoto Y, Welham N, Hirano S. Implantation of atelocollagen sheet for vocal fold scar. Curr Opin Otolaryngol Head Neck Surg. 2010;18:507--11. 11. Hirano S, Nagai H, Tateya I, Tateya T, Ford CN, Bless DM. Regen- eration of aged vocal folds with basic fibroblast growth factor in a rat model: a preliminary report. Ann Otol Rhinol Laryngol. 2005;114:304--8. 12. Hirano S, Kishimoto Y, Suehiro A, Kanemaru S, Ito J. Regenera- tion of aged vocal fold: first human case treated with fibroblast growth factor. Laryngoscope. 2008;118:2254--9. 13. Hirano S, Bless D, Heisey D, Ford C. Role of hepatocyte growth factor and transforming growth factor beta 1 in production of extracellular matrix by canine vocal fold fibroblasts. Laryngo- scope. 2003;113:144--8. 14. Kishimoto Y1, Hirano S, Kitani Y, Suehiro A, Umeda H, Tateya I, et al. Chronic vocal fold scar restoration with hepatocyte growth factor hydrogel. Laryngoscope. 2010;120:108--13. 15. Farran AJ, Teller SS, Jha AK, Jiao T, Hule RA, Clifton RJ, et al. Effects of matrix composition, microstructure, and vis- coelasticity on the behaviors of vocal fold fibroblasts cultured in three-dimensional hydrogel networks. Tissue Eng Part A. 2010;16:1247--61.

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