Engineered Muscle Actuators: Cells and Tissues - Biomimetics: Biologically Inspired Technologies - page 246

intracellular mechanisms. Muscle tissues provide the chemomechanical interface between muscle
cells and the environment. It is at the tissue level that muscle becomes a practical, responsive, and
robust actuator. Tissue level organization provides an ECM for the mechanical support and mechan-
otransduction of signals to and from the biomolecular motors within each cell. Specialized trans-
membrane structures transduce force from the arrays of biomolecular motors to the external
environment. Failures of these tissue-level structures result in severe pathology of muscle.
Muscle phenotype is known to be a result of a complex interaction between the muscle and its
environment. In the absence of the proper signals, muscle will rapidly degenerate. These signals
must include chemical signals, mechanical signals, and the activation pattern of the muscle itself.
The most important point is that these signals are mediated by the tissue interfaces, and thus it is
critical to understand, and to ultimately engineer, adequate tissue interfaces for muscle actuators.
The critical interfaces are:

1. Vascular: the primary chemical interface, necessary for sections larger than 0.4 mm in diameter.

Perfusion of muscle tissue is important for many reasons, including the removal of metabolically-
generated heat, delivery of circulating hormones and metabolic substrates, and removal of meta-
bolic byproducts.

2. Myotendinous (MTJ): the primary mechanical interface, necessary for mechano-transduction in

muscle, transmission of force and power to the environment without damage to the muscle cells, and
transmission of environmental loads to the muscle cells in such a way that the tissue can respond
favorably through functional adaptation. In fact, force and power are transmitted transversely into
the ECM surrounding each myofibril as well as directly into the tendon. The ECM extends to meet
the tendon and transmit this additional force and power. Derangements of these paths of force
transduction at any level in general will lead to pathologies of muscle or tendon or both, often
resulting in contraction-induced injury to muscle, as is the case in Duchenne muscular dystrophy.

3. Neuromuscular (NMJ): the primary sensing and control interface, nerve input to muscle plays a

dominant role in the control of muscle metabolism and phenotype.

9.3.1 Potential Classes of Living Muscle Actuators

There are four basic approaches to the use of muscle as a mechanical actuator: whole explanted
muscles, recellularized muscle ECM, muscle engineered in an artificial ECM, and self-organized
muscle tissue engineered in vitro . Each class of muscle actuator has technical advantages and
presents technical challenges:

9.3.1.1 Whole Explanted Muscles

Whole muscles are frequently explanted to in vitro test systems to carry out muscle tissue
evaluations. This is common practice in the pharmaceutical industry as well as in muscle research
laboratories around the world. These preparations do not qualify as muscle actuators, as they
generally have no provision to maintain the muscle explant for longer than a few hours, and they
are not configured in such a way that the muscle could perform useful external work. Such
preparations are a far cry from any practical actuator embodiments. It is possible, however, to
remove whole muscles from a variety of animals and maintain their contractile function for long
periods of time (weeks). The use of such explants as practical mechanical actuators was the focus of
preliminary work in biomechatronics at MIT in the year 2000.
Advantages: the tissue interfaces are intact and muscle can often be removed with neurovascular
pedicles to allow perfusion ex vivo .
Disadvantages: architecture is limited to that available in nature. Most natural muscles do not
have an architecture suitable for use external to the animal, often due to the tendon geometry or lack
of suitable tendons.
Potential applications: drug testing, actuator applications limited by natural architectures.