Biomedical Engineering Reference
In-Depth Information
3.1 INTRODUCTION
The loss or failure of an organ or tissue is one of the most frequent, devastating, and costly problems
in healthcare.
1
With the increase in life expectancy, the aging-associated tissue loss or degeneration
becomes more severe and frequent. The current therapeutic options to treat organ or tissue loss are
based on transplanting the organ, performing surgical reconstruction, or using artifi cial implants.
2
Despite the advances in the medical fi eld, all these therapeutic approaches display several limita-
tions, and, in the majority of cases, they relieve the symptoms but do not cure the disease, since they
are unable to provide tissue regeneration.
3
The application of cells as therapeutic agents for disease as well as for repair and regeneration
of tissues is one of the toughest challenges in modern therapeutics. Tissue engineering (TE) is an
emerging multidisciplinary technique that offers great potential for developing new therapeutic
strategies for the treatment of damaged tissues or organs.
4
TE combines engineering and life sci-
ence approaches to guide specifi c cells to grow into the required tissue arrangement
in vitro.
5
Syn-
thetic or natural biodegradable macromolecules are used to produce temporary scaffolds, which
provide a suitable environment for cells to eventually form the required functional tissue. Ideally, a
small number of cells are collected from patients, then seeded in a temporary scaffold where they
are expanded and cultured
in vitro
. During the
in vitro
culture period, biochemical and mechani-
cal stimulations are applied to the cell-scaffold construct in order to direct cell proliferation and
extracellular matrix (ECM) organization and to generate functional tissue-engineered constructs
that meet the physiological requirements before being implanted into patients. After implantation,
the tissue-engineered construct, integrated in the damaged area, would guide the formation of new
functional tissue. Alongside the new tissue formation, the scaffold undergoes degradation releasing
products that are readily incorporated in well-defi ned metabolic pathways, and more space is left
available for further tissue growth.
6
TE has demonstrated its great potential as a promising treatment for repair and regeneration of
tissues and organs.
7,8
The success of TE will have great impact on general healthcare and quality
of human life.
3.2 REQUISITES FOR ENGINEERING TISSUES
Cells, scaffolds, and culture environment are the three essential elements in engineering tissue con-
structs.
9
In an ideal situation, the patient himself is the cell source, eliminating all the problems regard-
ing biocompatibility and transmission of pathogens. Nevertheless, the number of cells that can be
obtained from certain tissues without causing donor site morbidity is generally very low. The use of
adult stem cells (ASCs) is a very promising option to overcome this problem. ASCs are undifferentiated
cells with a very high proliferation capacity found among differentiated cells in tissues or organs. These
cells have the capacity of self-renewing and differentiating to yield the major specialized cell types of
that tissue or organ. The presence of ASCs has been reported in several organs and tissues, such as the
periosteum,
10
bone marrow,
11
muscle,
12
skin,
13,14
brain,
15
and fat tissue.
16,17
At the moment there is an
increasing number of research focused on understanding the mechanisms that control the differentia-
tion of ASCs into particular cell types and their potential use in tissue-engineering strategies. The state
of the art for the research in this area has been reviewed elsewhere.
18,19
The culture environment is another crucial element when developing an tissue-engineered
construct. This environment must mimic the one found in the original tissue or organ as closely
as possible. Ultimately, cell behavior is dictated by the complex coordination of a panoply
of biochemical and biomechanical cues. In the fi eld of bone TE, some studies have shown that
applying perfusion systems to the constructs increases the expression of bone-related proteins by
providing fl ow-mediated mechanical stimuli
20,21
and enhancing transport of nutrients and waste
within the constructs. Other studies have shown that using bioreactors to apply cyclical load to the
constructs increases the expression of bone-related proteins, compared with the nonloading ones.
22
