Scope of tissue engineering - Biomedical Engineering Desk Reference - page 702

Mass transfer for constructs under direct compression is
expected to be better than for those cultured under
hydrostatic pressure or by the static culture approach.
The main parameters that must be set when using dy-
namic compression are the frequency of the applied
load, the strain or force used, and the duration of the
experiment.
New bioreactors can be developed that take advantage
of several different mechanical stimuli, as well as a good
culturing environment, all in one package. For example,
hydrostatic pressure could be combined with a rotating
bioreactor to create a stimulating environment that is
self-contained. Because scaffolds are already cultured in
a fluid medium, hydrostatic pressure could be applied
without removing anything from the sterile environment.
This reduces the chance of contamination as well as
limiting the amount of time needed to transfer the
scaffolds between a stimulation device and a culturing
environment. If the cells are fed in sufficient amounts
and are surrounded by a good environment, they will act
like native cells and secrete ECM into the scaffold pores.
The addition of bioactive peptides and growth factors in
the scaffolds will help matrix synthesis, especially in
conjunction with mechanical forces.
Most of engineered tissues are histologically similar to
natural tissues, but differ greatly in mechanical strength,
stiffness, and functional properties. The mechanical
properties of many tissues engineered to date are inferior
to those of native tissues. Skeletal muscle constructs
were demonstrated to have reasonable initial histology
but force generation an order of magnitude below the
native tissue [22] . Generally, such poor results are ob-
served when cells seeded onto scaffolds are cultured
under static conditions. Both morphology and force
generation of engineered heart tissue may be modified by
cyclic loading during construct development. It is nec-
essary to investigate the effect of mechanical condition-
ing of cells on cell-scaffold constructs and to quantify
their mechanical properties as well as their active force
capabilities. Fiber arrays made from absorbable, rubber-
like materials have been chosen for such an approach.
The scaffold materials will guide cell orientation and
provide mechanical support, and then degrade within
a certain time frame but not before the graft attained
sufficient mechanical strength.

7.4
7.3
7.2
7.1
7.0
6.9
6.8
6.7
6.6 0

14

12

10

8

6

4

2

0

50 100 150 200 250 300 350 400

Distance ( μ m)

Fig. 7.2-26 Mean interstitial pH and partial pressure of oxygen
(pO 2 ) profiles of 27-day-old tumors taken as one moves away
from the nearest blood vessel. Open symbols, pH; closed
symbols, pO 2 .

Mammalian cells are located within 100-200 m mof
blood vessels. This distance is the diffusion limit for
oxygen. Figure 7.2-26 shows the relationship between
the distance of tumor cells from nearby vessels and their
degree of hypoxia and acidosis [23] . One of the dominant
factors currently limiting clinical applications of tissue
engineering is the inability of the scaffold to construct de
novo a microvasculature. Tissue engineered constructs
also require a capillary network for cell maintenance and
function excluding those less than 100-200 m m thick,
which may be oxygenated by diffusion. Few clinical trials
in cardiac tissue engineering are due to unavailability of
scaffolds with large size and excellent capability of vas-
culature. The lack of capillary network connected to the
host tissue and the resulting poor, oxygen transport limit
the thickness of generated tissue constructs to w0.1 mm,
which is generally too thin for clinical application. The
mass transport issue limits the size of engineered tissues
to a millimeter scale at the largest, which is clinically
insufficient if a large mass of tissue or a whole organ
should be replaced. In some cases, the limitation of this
mass transport of nutrients leads to loss of more than
95% of transplanted cell types. Fat tissue represents
a highly vascularized tissue, and a volume-persistent
culture of adipose tissue can be successful only via early
vascularization of the cell-scaffold construct. A simple
solution to avoid considerable cell death in vivo, espe-
cially in the central area, is to utilize native tissues with
rich vascularity. Among them is the omentum which is
a fold of the peritoneum anchored to the stomach and
transverse colon that drapes over the small intestine. The
omentum is highly vascular, contains a relatively large
surface area, and is recruited to sites of intra-abdominal
abscess, perhaps to ''wall off'' the area and prevent dif-
fuse peritoneal contamination. The mesentery of the
small intestine that anchors the bowel to the body is also
vascular and supplies blood to the small intestine.

7.2.6.5 Neovascularization

Mammalian cells require oxygen and nutrients for their
survival. Tissues in the body, except for cartilage, over-
come issues of sufficient nutrient and waste exchange
with their surroundings by containing closely spaced
capillaries that provide conduits for convective transport
of nutrients and waste products to and from the tissues.