Tissue engineering - Biomedical Engineering Desk Reference - page 633

phase II/III clinical studies ( Winslow, 2000 ). The latest
developments include nanoencapsulated genetically engi-
neered macromolecules of poly (hemoglobin-catalase-
superoxide dismutase). Biodegradable polylactides and
polyglycolides are used as carriers leading to artificial red
blood cells containing hemoglobin and protective enzymes
( Chang, 2003 ). Furthermore, perfluorocarbons (PFC)
may be an alternative characterized by a high gas dissolving
capacity (O 2 ,CO 2 , and others), chemical and biological
inertness, and low viscosity. However, hemoglobin binds
significantly more oxygen at a given partial oxygen pres-
sure than can be dissolved in PFC. Research to create
functional substitutes for platelets by encapsulating
platelet proteins in lipid vesicles has also been conducted
( Baldassare et al., 1985 ). Finally, stem cells have the po-
tential to differentiate into the various cellular elements of
blood ( Thomson et al. ,1998 ).

Future perspectives

Fig. 7.1.2-4 Photograph of a living, tissue engineered heart valve
after 14 days of biomimetic conditioning in a pulse-duplicator-
bioreactor based on a rapidly biodegradable synthetic scaffold
material. (Reprinted with permission from Hoerstrup et al., 2000 .
Circulation 102: III-44-III-49.)

Current methods of transplantation and reconstruction
are among the most time-consuming and costly therapies
available today. Tissue-engineering offers future promise
in the treatment of loss of tissue or organ function as well
as for genetic disorders with metabolic deficiencies. Be-
sides that, tissue engineering offers the possibility of
substantial future savings by providing substitutes that
are less expensive than donor organs and by providing
a means of intervention before patients are critically ill.
Few areas of technology will require more in-
terdisciplinary research or have the potential to affect
more positively the quality and length of life. Much must
be learned from cell biology, especially with regard to
what controls cellular differentiation and growth and
how extracellular matrix components influence cell
function. Immunology and molecular genetics will con-
tribute to the design of cells or cell transplant systems
that are not rejected by the immune system. With regard
to the cell source, transplanted cells may come from cell
lines or primary tissue, from the patients themselves, or
from other human donors, animal tissue, or fetal tissue.
In choosing the cell source a balance must be found be-
tween ethical issues, safety issues, and efficacy. These
considerations are particularly important when in-
troducing new techniques in the tissue-engineering field
such as the generation of histocompatible tissue by
cloning (nuclear transfer) (Lanza et al. , 2002) or by the
creation of oocytes from embryonic stem cells ( Hubner
et al., 2003 ).
The materials used in tissue engineering represent
a major field of research regarding, e.g., polymer pro-
cessing, development of controlled-release systems, sur-
face modifications, and mathematical models possibly
predicting in vivo cellular events.

expected to be an attractive alternative for cardiovascular
tissue-engineering applications.

Blood
There is a critical need for blood cell substitutes since
donor blood suffers from problems such as donor
shortage, requirements for typing and cross-matching,
limited storage time, and, even more importantly in the
era of AIDS, infectious disease transmission. Oxygen-
containing fluids or materials as a substitute for red blood
cells offer important applications in emergency re-
suscitation, shock, tumor therapy, and organ preservation.
Several oxygen transporters are under investigation. He-
moglobin is a primary candidate, which not only serves as
the natural oxygen transporter in blood but also functions
in carbon dioxide transport, as a buffer, and in regulating
osmotic pressure. Early clinical trials of cell-free hemo-
globin were complicated by its lack of purity, instability,
high oxygen affinity, and binding nitric oxide (NO), lead-
ing to cardiovascular side effects. These problems have
been subsequently addressed by various chemical modi-
fications such as intra- and intermolecular cross-linking
using diacid, glutaraldehyde, or o -raffinose or conjugation
to dextran or polyethylene glycol. Because of the limited
hemoglobin availability, genetically engineered human
hemoglobin or hemoglobin from bovine sources may
represent a valid alternative. Several products are now in