L. Ribeiro et al.
Resultados y conclusiones:
Hay posibilidades muy interesantes para futuros tratamientos en
otorrinolaringología que aplican los conceptos de la ingeniería de tejidos.
© 2014 Elsevier Espa˜na, S.L.U. and Sociedad Espa˜nola de Otorrinolaringología y Patología
Cérvico-Facial. Todos los derechos reservados.
Introduction
In the current era the paradigm of medicine is constantly
changing, as new concepts and methods of life support
and disease control arise. Tissue engineering is becoming
one of the most promising weapons in medical practice.
Based on highly advanced technological procedures, tis-
sue and organ reconstruction may, within a short time,
become gold-standard treatments for a rising number of
medical conditions where classical pharmacological or surgi-
cal interventions have limited effectiveness. In fact, recent
developments in the area clearly show impressive results in
the rehabilitation of functionally or structurally committed
organs and tissues.
1
Otorhinolaryngology (ORL), as a medical specialty with a
wide range of medical and surgical interventions, naturally
assumes a position of leadership in the application of tissue
engineering techniques.
The aim of this review is the description of the fundamen-
tals of regenerative medicine and its potential applications
in ORL.
Fundamentals
The main goal of tissue engineering is restoring functional or
structural tissue by using living elements that will later be
integrated in patients.
1
In this process, 3 basic components
are generally present: cells, regulators/growth factors and
scaffolds, which may or may not be used simultaneously.
2,3
Cells
Most papers published within the past 20 years have focused
mainly on cell therapy,
1
which consists in the deposit of
selected living cells in an appropriate scaffold, that, when
exposed to a specific microenvironment, will multiply and
differentiate into the desired structure. Different cell sub-
types may be used: stem cells and adult cells.
1--3
Stem cells are characterized not only by their ability of
continuous and unlimited self-renewal, but also by the pos-
sibility of differentiation into any cellular phenotype.
2
Stem
cells are assumed as having the highest potential in regen-
erative medicine, although their use is limited by ethical
issues and the potential risk of neoplastic transformation.
Stem cells can be obtained from embryonic or mature tis-
sues. Embryonic stem cells are derived from blastocysts, and
therefore can differentiate into any mature cell type of the
3 germ layers.
4
On the other hand, adult stem cells can be
collected from certain niches in the body, namely bone mar-
row, adipose tissue or blood,
4
and are not totally pluripotent
as they are positioned in a later stage of the differentiation
line, having a finite capacity to multiply depending on the
origin of the tissue.
Adult cells can be obtained from a biopsy specimen of
the tissue to be regenerated, and their replication is induced
in vitro
before transplantation. Being phylogenetically more
advanced, adult cells do not have the ability to replicate
endlessly or to transform into different cell types. These
features, combined with the possibility of perpetuation of
pre-existing pathological changes in the donor organ or tis-
sue, represent important limitations in their use.
Regulators/Growth Factors
Growth factors are molecules that regulate proliferation,
differentiation and cell function, and therefore may induce,
accelerate or inhibit those cellular processes. They are an
essential element in regenerative medicine. Depending on
the technique used, these molecules can be included in
a scaffold, which serves as a means for their controlled
release, which will influence and control cell growth.
3
Scaffolds
Scaffolds are porous 3-dimensional structures that provide
mechanical support and physical protection to cells and
growth factors.
2
These should be composed of a biocom-
patible and reabsorbable matrix,
1,2,5
allowing for complete
tissue regeneration. Collagen and fibrin are among the most
commonly used materials, and are generally obtained from
natural sources; polyglycolic acid, a synthetic polymer, may
also be used.
2
Applications of Tissue Engineering
in Otorhinolaryngology
Laryngology
The vocal folds are able to vibrate at a frequency up to
1000 Hz
3
, due to their microstructure consisting of epithe-
lium, lamina propria and the vocal muscle. The lamina
propria is composed by a superficial layer (Reinke space), an
intermediate layer and a deeper layer, each of these having
specific cellular components, which are ultimately related
to the organ function.
The stratified epithelium covers the entire surface of the
vocal folds, and represents a barrier against physical, chemi-