Biomedical Engineering Reference
In-Depth Information
Unfortunately, to the disappointment of everyone involved, we must today reconcile the fact
that cell-based therapies and tissue engineering have not lived up to the promises the pioneers of
tissue engineering communicated two decades ago.
2
Although there have been some successes,
it is widely recognized that tissue engineering is not yet showing signifi cant progress in terms of
clinical outcomes and commercialization. Part of the problem has been that we have failed to fully
understand what regenerative medicine really means and to appreciate that regeneration here is
synonymous with creation. More importantly, cell transplantation and the scaffold-based tissue
engineering processes, for example, involve many different phases and substantially different sci-
entifi c inputs, such that there has been insuffi cient integration of these phases within any holistic
regenerative medicine technology platform.
1
Two major problems, within such a holistic technology
platform, that tissue engineers need to overcome are (1) problems associated with “scale-up”
3,4
and
(2) cell death of a signifi cantly high number of cells after implantation.
4
From an engineering point of view, large numbers of cells are needed to generate relatively
small volumes of tissues. To ultimately be effective in patients, it is necessary to generate relatively
large volumes of so-called neotissue, starting with very few cells. Differentiated cells, expanded
in vitro
under modern cell-culture protocols, more often than not lose effi cacy. Cell implantation and
its associated vascular disruption result in a relatively hypoxic host environment and subsequently
lead to fast necrosis of a large number of the implanted cells. Hence, the potential for different cell
types to be expanded
in vitro
and stay alive in a relatively hostile environment at the time of implan-
tation is now being studied not only from a qualitative but also from a quantitative point of view. To
be effective, cells should be easily procured, effectively expanded
in vitro
, survive the implantation,
not be recognized as foreign, function normally, and not become malignant. In addition, it would
also be quite convenient if no moral concerns or questions were generated as a result of the cell type
used. There is a considerable debate concerning different cell sources. Mature cells have a relatively
high oxygen requirement and a low potential for expansion (scale-up). Alternatively, there are several
sources of “immature” cells. Immature cells commonly refer red to as stem or progenitor cells may be
classifi ed as embryonic in origin or adult somatic stem cells. Despite being under great moral debate,
the fact remains that embryonic and adult stem cells may have very similar potential to develop into
the different cellular elements necessary for structural and functional tissue regeneration. Embryonic
stem cells have been postulated to retain a greater ability to produce a healthier tissue. At this point
in time, there is little evidence to support the goal that embryonic stem cells can be consistently
driven to form only the cell type needed for the tissue to be engineered. Several excellent reviews
5-7
and topics
8
have summarized the current knowledge on embryonic and adult somatic stem cells.
2.1.1 S
CAFFOLD
-B
ASED
T
ISSUE
E
NGINEERING
It can be argued that the beginning of the “scaffold-based tissue engineering concept”—as we know
it today—was in the mid-1980s when Dr. Joseph Vacanti of the Children's Hospital approached
Dr. Robert Langer of Massachusetts Institute of Technology (MIT) with an idea to design scaffolds
for cell delivery as opposed to seeding cells onto, or mixing cells into the currently available natu-
rally occurring matrices, which possessed physical and chemical properties that were diffi cult to be
manipulated, resulting in wide variations of the results produced
in vitro
and
in vivo
.
4,9
Today, scaffold-based tissue engineering concepts involve the combination of viable cells,
biomolecules, and a scaffold to promote the repair and regeneration of tissues as depicted sche-
matically in Figure 2.1. The two
in vivo
images at the bottom show a medical grade polycapro-
lactone-tricalcium phosphate (mPCL-TCP) composite scaffold (14 mm
5 mm) being
inserted during pig surgery in a spinal fusion model and also an FDA-approved mPCL scaffold
(50 mm
×
12 mm
×
2 mm) being utilized during human orbital fl oor fracture repair. The scaffold
(Osteopore, Singapore) is intended to support cell migration, growth and differentiation, and guide
tissue development and organization into a mature and healthy state. The science behind engineer-
ing tissue-engineered constructs (TECs) is still in its relative infancy, and various approaches and
×
50 mm
×
