Biomedical Engineering Reference
In-Depth Information
are proposed to play a role in the repair of vessel walls.
98,99
The signals that trigger the release of
these EPCs are being discovered (stromal cell-derived factor-1, SDF1), and this opens a new pos-
sibility to obtain an increased number of EPCs on the surface of the device, forming an endothelial
layer. Devices that depend on spontaneous endothelialization are often referred to as off-the-shelf-
implants. This means they can be employed instantaneously, are relatively cheap, and no specialized
infrastructure is required for its use.
Another strategy involves the isolation of endothelial cells from a vessel biopsy conducted on
the patient. The endothelial cells are isolated and multiplied in the laboratory. These cells are then
seeded on the surface of the device, and subsequently the device is implanted. In some cases the
endothelial cells are allowed to adhere and proliferate on the surface for several days in the labora-
tory before implantation is performed. A major disadvantage of such a strategy is that two opera-
tions are required, increasing the risk of infection and also increasing the total cost of the procedure.
Though this endothelial cell-seeded vascular grafts performed well in animal models, the results
in humans were disappointing.
100,101
One of the reasons for this difference in performance might be
that in animal models, mostly young, healthy animals are used. In the clinic, the situation is very
much different. The patients, who have to be treated, are frequently not in good condition. This
means that harvesting of healthy endothelial cells from these patients is not easy, and in general
yields are low. Additionally, these patients often have other diseases like diabetes that can dramati-
cally infl uence the success rate of these synthetic vascular grafts. The step from the animal models
toward the treatment of human patients has been a very diffi cult one and the simple strategy of seed-
ing autologous endothelial cells has proven to be complicated and often unsuccessful. Because of
the shortcomings of these cell-seeding experiments some scientists have reverted to tissue engineer-
ing, with which they attempt to construct fully biological and functional tissues
in vitro
. No doubt,
in the future tissue engineering will produce functional tissues that can replace blood-contacting
tissues, but at this moment success in this fi eld seems distant.
17.6.4 T
ISSUE
E
NGINEERING
Since the purpose of this chapter is not to fully clarify tissue engineering, this topic will not be
discussed in too much detail. However, there are many biomedical engineers trying to produce
alternatives for blood-contacting devices using tissue engineering.
The
in vitro
production of functional tissues is a relatively new fi eld within the science of biomedi-
cal engineering, called tissue engineering. The basic idea is that on a synthetic, porous scaffold cells
are seeded and allowed to grow and differentiate, forming new functional tissue. These tissue-engi-
neered products are then implanted into the patient, restoring the defect or replacing diseased tissues.
The scaffold used is often biodegradable, so that no synthetic surfaces are left in the end. There are
several tissue-engineered products that are pursued, which could act as an alternative for blood-con-
tacting devices. Vascular prostheses, heart valves, pieces of heart muscle are all subjects of intense
investigation. Almost a decade ago, the group of L'Heureux and coworkers has already succeeded
in producing a complete tissue-engineered blood vessel.
102
Though the
in vivo
performance was not
optimal, but the proof of principle was delivered. The biggest problem of all these tissue-engineering
strategies is that the cells have to grow all the way through the scaffold, adopting the right differen-
tiation at the right time. This has proven to be the hardest to achieve. The development of incubators
that mimic the blood fl ow and conditions encountered by the native tissue (mechanic stress by beating
heart, pulsatile shear stress by fl owing blood) has greatly improved the survival of cells and formation
of tissues.
103,104
The option to perform the incubation in the body has also been shown in mice, in case
of vascular grafts.
105
But it does not seem very likely that such a strategy will be applied in large scale
with patients very soon. Another problem is that the scaffold in which the cells are seeded has to be
degraded at exactly the right time. Otherwise the consequences can be disastrous. Imagine the scaf-
fold of a tissue-engineered coronary artery degrading prematurely.
