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252 Biomimetics: Biologically Inspired Technologies

organ culture and when properly employed are effective for long-term maintenance of living
tissue ex vivo.

9.6.2.2 Mechanical Failure within the Tissue (Intracellular, ECM)

Also known as contraction-induced injury, this mode of failure is prevalent in muscle tissue
subjected to maximal contractions during forced lengthening, and affects all classes of muscle
actuators. The effective countermeasure involves employing control algorithms that prevent
repeated eccentric contraction of fully activated muscle actuators. Living muscle can functionally
adapt to tolerate lengthening contractions if the proper maintenance protocols are employed. An
attempt can be made to implement such protocols in the muscle actuator bioreactors using feedback
control.

9.6.2.3 Mechanical Failure at the Tissue Interface

Less common for muscle in vivo, this is a major failure mode for explanted and engineered tissues
in general. For whole explanted muscles, the interface typically involves suture or adhesive applied
to the preexisting tendons. Lack of process control in this tissue or synthetic junction leads to
unpredictable mechanical failures over time. In engineered tissues the problem is more serious, as
tissue failure frequently occurs at the tissue or synthetic interface under relatively mild mechanical
conditions. We have extensive experimental data on this failure mode in engineered muscle tissue
subjected to external loading. We hypothesize the failure to be due to stress concentration at the
tissue or synthetic interface, compounded by inadequate force transduction from the appropriate
intracellular force generating machinery to the extracellular synthetic load bearing fixtures, leading
to cell membrane damage at the interface with subsequent rapid tissue degradation and necrosis.
The best countermeasure requires the engineering of a muscle–tendon interface (MTJ), which is a
major objective of current research in muscle tissue engineering. Tendon tissue is 80 to 90% ECM,
composed chiefly of parallel arrays of collagen fibers. The tendon-to-synthetic interface, where
biology meets machine, is a separate and equally important technical challenge.

9.6.2.4 Metabolic Failure

This failure mode results most frequently from inadequate delivery of metabolic substrates and
inadequate clearance of metabolic byproducts, and is exacerbated at elevated temperatures. The
best countermeasure for this failure mode is to restrict the muscle actuator cross-section to more
than approximately 200 mm diameter, or to provide perfusion through a vascular bed in the case of
larger cross-sections. This mode of failure typically initiates at the axial core of cylindrical muscle
actuators. For this reason, sustained angiogenesis and perfusion is a major technical objective in
current tissue engineering research.

9.6.2.5 Cellular Necrosis and Programmed Cell Death

Several controllable circumstances can lead to this general mode of failure in all classes of muscle
actuators. Cellular hypercontraction and hyperextension in muscle results in rapid necrosis. This
mechanism will occur more or less uniformly across the muscle cross-section, but will theoretically
occur more frequently in areas with reduced physiologic cross-sectional area or inhibited sarco-
meric function. This failure mode can be prevented by control of the internal mechanical compli-
ance and stroke of the muscle actuator. Muscle maintained at an inappropriate length, either too
short or too long, will deteriorate, even if the muscle is quiescent. In explanted muscles, mainte-
nance at lengths greater than the plateau of the length–tension curve appears to be the most
damaging over time.