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258 Biomimetics: Biologically Inspired Technologies

be implanted at the ultimate site for which it is intended, however, it is essential to consider the
morbidity of the site at which the disuse will be initially developed.

9.9.3 Engineered Tissue Interface: Tendon

The MTJ is critical for the ability of muscle tissue to transduce force to and from the external
environment, and to produce maximal power without subsequent injury to the muscle cells in
the contractile tissue. The MTJ contains specialized structures at the cell membrane which
facilitate transmembrane transmission of force from the contractile proteins (biomolecular
motors) within the cell to the surrounding collagen fibrils in the ECM (Trotter, 1993). These
structures include a large number of infoldings of the muscle cell membrane at the MTJ, increasing
the membrane surface area and acting to transfer stress from the cytoskeleton to the ECM in
the tendon. These structures have also been demonstrated to occur when myotubes are cocultured
with fibroblasts concentrated near the ends of the muscle constructs in vitro (Swasdison and
Mayne, 1991). In the case of whole explanted muscle actuators, the MTJ already exists, and it
is necessary to maintain this structure in vitro. In all other classes of muscle actuator it is
necessary to generate or regenerate the MTJ and tendon structures. Currently, attempts to engineer
tendon-like structures and muscle–tendon junctions in culture follow one of three distinct
approaches:

(1) Scaffold-based tendon, used as an anchor material for engineered muscle.
(2) Self-organizing tendon and muscle-tendon structures in co-culture.
(3) Direct laser transfer of muscle and tendon cells into defined 3-D structures.

9.9.4 Nerve–Muscle Interfaces

Skeletal muscle phenotype is defined largely by the motor nerve which innervates each muscle
fiber. Adult muscles may be either fast- or slow-twitch, but in general in humans muscles are
mixed, containing significant populations of both fast- and slow-twitch fibers. Denervated muscle
rapidly loses tissue mass and the adult phenotype, with contractility eventually dropping to
essentially zero. Although it is possible to maintain adult phenotype of adult skeletal muscle in
the absence of innervation, it is not yet clear whether it is possible to guide skeletal muscle
tissue development to an adult phenotype in an entirely aneural culture environment. For that
reason, nerve–muscle synaptogenesis in culture is an area of active research in tissue engineering.
Putative synaptic structures in vitro have been reported for decades (Ecob et al., 1983; Ecob, 1983,
1984; Ecob and Whalen, 1985), in some cases axon sprouting from nerves to muscle tissue
in culture is clearly visible (Figure 9.2) and verified upon histologic examination; however,
functional nerve–muscle in vitro systems that result in advanced tissue development have yet to
be demonstrated.

9.9.5 Tissue–Synthetic Interfaces

Another key challenge is to develop means to mechanically interface living muscle cells and tissues
to synthetic fixtures in such a way that the tissue development and function will not be inhibited.
The technical challenge is to provide a transition of mechanical stiffness and cell density in the
region between the contractile tissue and the synthetic fixture, to reduce stress concentrations at the
tissue interface and provide mechanical impedance matching. Several approaches are currently
under investigation, including the chemical functionalization of synthetic surfaces to bind collagen,
and the use of porous scaffolds to promote tissue in-growth at the desired tissue or synthetic
interface.