Tissue engineering - Biomedical Engineering Desk Reference - page 630

meshes and conditioned for several weeks on an orbital
shaker. The functional cartilage was then combined with
an osteoconductive support made of ceramic/collagen
sponge. The composite was press-fitted in a large ex-
perimental osteochondral injury in a rabbit knee joint,
where it showed good structural and functional proper-
ties ( Schaefer et al. , 2002 ). With regard to the needs
of reconstructive surgery, tissue-engineered autologous
cartilage has been generated in vitro from tiny biopsies
( Naumann et al. , 1998 ). Finally, some research has been
undertaken to evaluate tissue engineering of cartilage
even in space in order to elucidate the influence of micro/
agravity on tissue formation ( Freed et al. , 1997 ).

Abundant callus formation along the implants and good
integration at the interface with the host bones was ob-
served 2 months after surgery ( Quarto et al., 2001 ).

Muscle
The ability to generate muscle fibers has possible appli-
cation regarding the treatment of muscle injury, cardiac
disease, disorders involving smooth muscle of the in-
testine or urinary tract, and systemic muscular diseases
such as Duchenne muscular dystrophy (DMD). Myo-
blasts from unaffected relatives have been transplanted
into Duchenne patients and shown to produce dystro-
phin several months following the implantation. Myo-
blasts can migrate from one healthy muscle fiber to
another ( Gussoni et al. , 1992 ); thus, cell-based therapies
may be useful in treating muscle atrophies. Creation of
a whole hybrid muscular tissue was achieved by a se-
quential method of centrifugal cell packing and me-
chanical stress-loading resulting in tissue formation
strongly resembling native muscle in terms of cell
density, cell orientation, and incorporation of capillary
networks. Kim and Mooney (1998) demonstrated with
regard to smooth muscle cells the importance of matching
both the initial mechanical properties and the degradation
rate of a predefined three-dimensional scaffold to the
specific tissue that is being engineered.
Loss of heart muscle tissue in the course of ischemic
heart disease or cardiomyopathies is a major factor of
morbidity and mortality in numerous patients. Once
patients become symptomatic, their life expectancy is
usually markedly shortened. This decline is mostly
attributed to the inability of cardiomyocytes to
regenerate after injury. Necrotic cells are replaced by
fibroblasts leading to scar tissue formation and regional
contractile dysfunction. In contrast, skeletal muscle has
the capacity of tissue repair, presumably because of
satellite cells that have regenerative capability. Satellite
cells are undifferentiated skeletal myoblasts, which are
located beneath the basal lamina in skeletal muscles.
These cells have also been tested for myocardial repair
( Chiu et al. , 1995 ; Menasche, 2003 ; Menasche et al. ,
2001; Taylor et al. , 1998 ). In rats, myoblast grafts can
survive for at least 1 year ( Al Attar et al. , 2003 ). How-
ever, satellite cells transplanted into nonreperfused scar
tissue do not transdifferentiate into cardiomyocytes but
show

Bone
Current therapies of bone replacement include the use of
autogenous or allogenic bone. Moreover, metals and ce-
ramics are used in several forms: biotolerant (e.g., tita-
nium), bioresorbable (e.g., tricalcium phosphate), porous
(e.g., hydroxyapatite-coated metals), and bioactive (e.g.,
hydroxyapatite and glasses). Synthetic and natural poly-
mers have been investigated for bone repair, but it has
been difficult to create a polymer displaying optimal
strength and degradation properties. Another approach
involves implantation of demineralized bone powder
(DBP), which is effective in stimulating bone growth. By
inducing and augmenting formation of both cartilage and
bone (including marrow), bone morphogenic proteins
(BMPs) or growth factors such as transforming growth
factor-b (TGF-b) represent other promising strategies
( Toriumi et al. , 1991 ; Yasko et al. , 1992 ). Bone growth
can also be induced when cells are grown on synthetic
polymers and ceramics. For example, when human
marrow cells are grown on porous hydroxyapatite in
mice, spongious bone formation was detectable inside
the pores within 8 weeks ( Casabona et al. , 1998 ). Fem-
oral shaft reconstruction has been demonstrated using
bioresorbable polymer constructs seeded with osteo-
blasts as bridges between the bone defect ( Puelacher
et al. , 1996 ), and similar experiences have been reported
for craniofacial applications ( Breitbart et al. , 1998 ).
Formation of phalanges and small joints has been dem-
onstrated with selective placement of periosteum,
chondrocytes, and tenocytes into a biodegradable syn-
thetic polymer scaffold ( Isogai et al. , 1999 ). Large bone
defects in tibia of sheep were successfully reconstructed
using combinations of autologous marrow stromal cells
and coral ( Petite et al. , 2000 ). Similar results were
obtained by Kadiyala et al. , who have treated experi-
mentally induced nonunion defects in adult dog femora
with autologous marrow-derived cells grown on a hy-
droxyapatite: beta tricalcium phosphate (65: 35) scaffold
( Kadiyala et al. , 1997 ). This approach was also successful
in

a switch to slow-twitch fibers, which allow

sustained improvement in cardiac function ( Hagege

et al. , 2003 ; Reinecke et al. , 2002 ).
Recent studies have suggested that bone marrow-
derived or blood-derived progenitor cells contribute to
the regeneration of infarcted myocardium and enhance
neovascularization of ischemic myocardium ( Kawamoto
et al. , 2001 ; Orlic et al. , 2001a , b). In a pilot trial it was
shown

patients suffering from segmental bone defects.

that also in patients with reperfused acute