Tissue Engineering in Otorhinolaryngology
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.
Scaffolds
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.
Conclusion
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
embryonic stem cells, and to clarify long-term safety profiles
of these promising biomaterials.
Conflict of Interest
The authors declares no disclosures.
Acknowledgments
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.