Tissue engineering - Biomedical Engineering Desk Reference - page 625

In extracorporeal systems (vascular or flow-through
designs) cells are usually separated from the blood-
stream. Great progress is being made in the development
of extracorporeal liver assist devices for support of pa-
tients with acute liver failure. Currently four devices that
rely on allogenic or xenogenic hepatocytes cultured in
hollow-fiber membrane technology are in various stages
of clinical evaluation (Patzer, 2001; Rozga et al. , 1994 ).

cell-polymer matrix is prevascularized or would become
vascularized as the cell mass expands after implantation.
Vascularization could be a natural response to the implant
or be artificially induced by sustained release of angio-
genic factors from the polymer scaffold ( Langer and
Vacanti, 1999 ). Since the polymer scaffold is designed to
be biodegradable, concerns regarding long-term

biocompatability are obviated.
Cells used in tissue engineering may come from a va-
riety of sources including cell lines from the patients
themselves (autologous), human donors (allogeneic), or
animal sources (xenogeneic). However, allogeneic and
xenogeneic tissue may be subjected to immunorejection.
Cell-surface modulation offers a possible solution to this
problem by deleting immunogenic sites and therefore
preventing immunorecognition. A bank of cryopreserved
cells would then be possible and genetic engineering
techniques could be used to insert genes ( Raper and
Wilson, 1993 ) to replace proteins, such as the LDL re-
ceptor ( Chowdhury et al. , 1991 ) or factor IX ( Armen-
tano et al. , 1990 ).

Tissue engineering using scaffold
biomaterials

Open systems of cell transplantation with cells being in
direct contact to the host organism aim to provide
a permanent solution to the replacement of living tissue.
The rationale behind the use of open systems is based on
empirical observations: dissociated cells tend to reform
their original structures when given the appropriate en-
vironmental conditions in cell culture. For example, cap-
illary endothelial cells form tubular structures and
mammary epithelial cells form acini that secrete milk on
the proper substrata in vitro ( Folkman and Haudenschild,
1980 ). Although isolated cells have the capacity to
reform their respective tissue structure, they do so only
to a limited degree since they have no intrinsic tissue
organization and are hindered by the lack of a template to
guide restructuring. Moreover, tissue cannot be trans-
planted in large volumes because diffusion limitations
restrict interaction with the host environment for nu-
trients, gas exchange, and elimination of waste products.
Therefore, the implanted cells will survive poorly more
than a few hundred microns from the nearest capillary or
other source of nourishment ( Vacanti et al. , 1988 ). With
these observations in mind, an approach has been de-
veloped to regenerate tissue by attaching isolated cells to
biomaterials that serve as a guiding structures for initial
tissue development. Ideally, these scaffold materials are
biocompatible, biodegradable into nontoxic products,
and manufacturable ( Rabkin et al. , 2002 ). Natural ma-
terials used in this context are usually composed of ex-
tracellular matrix components (e.g., collagen, fibrin) or
complete decellularized matrices (e.g., heart valves,
small intestinal submucosa). Synthetic polymer materials
are advantageous in that their chemistry and material
properties (biodegradation profile, microstructure) can
be well controlled. The majority of scaffold-based tissue
engineering concepts utilize synthetic polymers [e.g.,
PGA, poly(lactid acid) (PLA), or poly(hydroxy alka-
noate) (PHA)]. In general, these concepts involve
harvesting of the appropriate cell types and expanding
them in vitro, followed by seeding and culturing them on
the polymer matrices. The polymer scaffolds are
designed to guide cell organization and growth allowing
diffusion of nutrient to the transplanted cells. Ideally, the

Applications of tissue engineering

Investigators have attempted to engineer virtually every
mammalian tissue. In the following summary, we discuss
replacement of ectodermal, endodermal, and mesoder-
mal derived tissues.

Ectodermal derived tissue

Nervous system
Diseases of the central nervous system, such as a loss of
dopamine production in Parkinsons's disease, represent
an important target for tissue engineering. Trans-
plantation of fetal dopamine-producing cells by stereo-
tactically guided injection into the appropriate brain
region has produced significant reversal of debilitating
symptoms in humans ( Lindvall et al. , 1990 ). Further
benefit regarding survival, growth, and function has
been demonstrated when implantation of dopamine-
producing cells was combined with polymer-encapsulated
cells continuously producing human glial cell line-derived
growth factor (GDNF) ( Sautter et al. ,1998 ). In the
animal model PC12 cells, an immortalized cell line de-
rived from rat pheochromocytoma, have been encapsu-
lated in polymer membranes and implanted in the guinea
pig striatum ( Aebischer et al. , 1991 ) or primates ( Date
et al. , 2000 ; Kordower et al. , 1995 ), resulting in a dopa-
mine release from the capsule detectable for many
months. Similarly, encapsulated bovine adrenal chro-
mafin cells have been implanted into the subarachnoid
space in rats, where through their continuous production