Tissue engineering - Biomedical Engineering Desk Reference - page 623

Current therapeutic approaches
for lost tissue or organ function

artificial implants can provide a significant growth or
remodeling potential, which often results in repeated
operations associated with substantial morbidity and
mortality ( Mayer, 1995 ).

Transplantation

Supplementation of metabolic products
of diseased tissues or organs

Organs or parts of organs are transplanted from a cadav-
eric or living-related donor into the patient suffering from
lost organ function. Many innovative advances have been
made in transplantation surgery during recent years and
organ transplantation has been established as a curative
treatment for end-stage diseases of liver, kidney, heart,
lung, and pancreas ( Starzl, 2001 ; Starzl et al. , 1989 ;
Stratta et al. , 1994 ). Unfortunately, transplantation is
substantially limited by a critical donor shortage. For ex-
ample, fewer than 5200 liver donors are available annually
for the approximately 18,500 who were on the waiting
list in the year 2001 ( http://www.ustransplant.org/
annual.html ). Besides the donor shortage, the other major
problem of organ transplantation remains the necessity of
lifelong immunosuppression therapy with a number of
substantial and serious side effects ( Keeffe, 2001 ).

In the case of the loss of endocrine tissue function, hor-
monal products such as insulin or thyroid, adrenal, or
gonadal hormones can be successfully supplemented by
oral or intravenous medication. In most cases, chronic
supplementation is necessary. Unfortunately, supple-
mentation therapy cannot replace natural feedback
mechanisms, frequently resulting in dysregulation of
hormone levels. As a consequence, clinical conditions
such as hypo- or hyperglycemic crises or the long-term
complications of chronic hormonal imbalances nephrop-
athy or microvascular disease in patients with insulin-
dependent diabetes mellitus continue to occur ( Orchard
et al. , 2002 , 2003).

Tissue engineering as an approach
to replace lost tissue or organ
function

Surgical reconstruction

Organs or tissues are moved from their original location
to replace lost organ function in a different location (e.g.,
saphenous vein as coronary bypass graft, colon to replace
esophagus or bladder, myocutaneous flaps or freegrafts
for plastic surgery). Nevertheless there are a number of
problems associated with this method of therapy, since
the replacement tissues, consisting of a different tissue
type, cannot replace all of the functions of the original
tissue. Moreover, long-term complications occur, such as
the development of a malignant tumor in colon tissue
replacing bladder function ( Kato et al. , 1993 ; Kusama
et al., 1989) or calcification and resulting stenosis of
vascular grafts ( Kurbaan et al., 1998 ). Finally, there is also
the risk of complications and surgical morbidity at the
donor site.

In the most frequent paradigm of tissue engineering,
isolated living cells are used to develop biological sub-
stitutes for the restoration or replacement of tissue or
organ function. Generally, cells are seeded on bioab-
sorbable scaffolds, a tissue is matured in vitro, and the
construct is implanted in the appropriate anatomic
location as a prosthesis. Cells used in tissue engineering
may come from a variety of sources including application-
specific differentiated cells from the patients themselves
(autologous), human donors (allogeneic) or animal sources
(xenogeneic), or undifferentiated cells comprising pro-
genitor or stem cells. The use of isolated cells or cell
aggregates enables manipulation prior to implantation,
e.g., transfection of genetic material or modulation of the
cell surface in order to prevent immunorecognition.
Three general strategies have been adopted for the cre-
ation of new tissues including cell injection, closed, or
flow-through systems, and tissue engineering using bio-
degradable scaffolds.

Artificial prosthesis

The use of artificial, nonbiological materials in mechani-
cal heart valves, blood vessels, joint replacement pros-
theses, eye lenses, or extracorporeal devices such as
dialysis or plasmapheresis machines has improved and
prolonged patients' lives dramatically. However, these
methods are complicated by infection, limited durability
of the material, lack of mechanism of biological repair
and remodeling, chronic irritation, occlusion of vascular
grafts, and the necessity of anticoagulation therapy and
its side effects ( Kudo et al., 1999 ; Mow et al., 1992 ).
Regarding

Cell injection method

The cell injection method avoids the complications of
surgery by allowing the replacement of only those cells
that supply the needed function. Isolated, dissociated
cells are injected into the bloodstream or a specific organ
of the recipient. The transplanted cells will use the

the pediatric patient population, not all