Biomedical Engineering Reference
In-Depth Information
techniques to verify the presence of one or more critical subcellular constituents is simply not
an adequate demonstration of end organ function. Thus, it is important to develop the neces-
sary facilities to actually quantify the organ-level function of tissue engineered constructs.
Of course, different tissues and organ systems have different functions. When designing a
tissue or organ, it is therefore essential to develop a design specification for the engineered
tissue, with well-defined, quantitative functional assessments, also called “figures of merit
(FoM),” as well as a defined method by which to assess these values.
Presumably, the tissues or organs will be cultured for some time prior to their use to
permit growth and development. Many tissues have measurable function that changes
during development, so it is most desirable to identify one or more quantities that may be
measured nondestructively during the course of the development of the tissues in culture.
A specific example is instructive: the contractility of mammalian skeletal muscle changes
throughout the early stages of development into adulthood. Muscle phenotype is defined
largely by the myosin heavy chain content of individual muscle fibers, but these can be quan-
titatively inferred by nondestructive measurements of the isometric and dynamic contractility
of the muscle tissue. The same is true for tendon. The tangent modulus, tensile strength, and
fracture toughness increase during development, whereas the size of the “toe region” of the
stress strain curve tends to decrease, presumably due to the increasingly well-ordered colla-
gen structure during pre- and early postnatal development. It is not possible to nondestruc-
tively test the tensile strength and fracture toughness of a cultured tendon specimen, but
the tangent modulus and the characteristics of the toe region can be readily measured with
minimal disruption to the tendon tissue in culture. With musculoskeletal tissues it often hap-
pens to be the case that the electromechanical signals that are required for nondestructive
quantitative assessment of the tissues in culture are essentially the same as those that would
be applied chronically to the tissues in culture to guide and promote development. For exam-
ple, electrically elicited contractions of skeletal and cardiac muscle are currently in use in an
attempt to promote development, and the application of mechanical strain has been used
since the 1980s on many musculoskeletal (muscle, bone, tendon, cartilage, ligament) and car-
diovascular tissues to promote development in culture.
An important future challenge is to develop bioreactor systems that permit the application
of the stimulus signals, while simultaneously allowing the functional properties of the tissues
to be nondestructively measured and recorded. If the functional properties of the developing
tissue are measured in real-time in a bioreactor system, it then becomes possible to assess the
current developmental status of each tissue specimen and to use this information to modify
the stimulus parameters accordingly. This permits stimulus feedback control of the tissue
during development and represents a significant increase in the level of sophistication and
effectiveness of functional tissue engineering technology. This constitutes an important aspect
of current research in the areas of both musculoskeletal and cardiovascular functional tissue
engineering.
6.6.3 Bioartificial Liver Specifics
The development of bioartificial liver (BAL) devices arose from the fact that “backup”
systems to replace deficient liver functions are nonexistent, in contrast to other tissue in
which duplications exist (e.g., as dual lung lobes, two kidneys, fibular crutches). The liver
