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Engineered Muscle Actuators 247

9.3.1.2 Recellularized Muscle Extracellular Matrix

Under ideal conditions in this process, muscle cells are chemically removed from the tissue, leaving
the ECM intact. The matrix would then presumably provide a perfect scaffold for the reintroduction
of suitable myogenic cells. In preliminary experiments it has been demonstrated that the acellular-
ized muscle matrix is entirely nonantigenic, so scaffolds can be removed from one animal and
implanted in another without fear of tissue rejection.
Advantages: The ECM retains much of the complex physical architecture of the tissue inter-
faces, so currently it is hypothesized that it will facilitate the reformation of suitable myotendinous
and neuromuscular junctions and vasculature for the creation of tissues suitable for surgical repair
of lost or damaged muscle tissue. Because the ECM is nonantigenic, it will be possible to remove
intact muscle structures from cadavers and acellularize them to form scaffolds for the reengineering
of living muscle tissue from the intended recipient, using the recipient’s cells (from a biopsy or
other method) to preclude subsequent postsurgical tissue rejection. Genetically engineered muscle
cells, cells from established cell lines, and primary cells may be reintroduced, as dictated by the
actuator application. The existing ECM structure of the acellularized vascular bed allows the
acellular muscle to be directly perfused.
Disadvantages: Like whole explanted muscles, the architecture of these actuators is defined by
the ECM, and therefore is limited to those forms available in nature. The acellularization process
may damage some of the important chemical messages on the matrix, so this method needs to be
optimized with this in mind.
Potential applications: Recellularized ECM actuators have the complex architecture of
whole muscles in vitro, and can be recellularized using cells isolated from any animal, so they
would be perfectly suited for engineering complex muscles for surgical transplantation, such
as facial muscles. The acellularization process can be readily carried out on cadaveric muscle,
so donor tissue availability should present no difficulties whatsoever, thus this class of
muscle actuators presents a very promising approach for engineering muscle for surgical trans-
plantation. The acellularized matrix could be repopulated with cells donated (and subsequently
amplified in culture) by the recipient of the transplant, thereby totally eliminating the risk of tissue
rejection.

9.3.1.3 Muscle Cultured in an Artificial Matrix

A wide range of matrices are available for engineered tissues, but most are unsuitable for
engineered muscle due to their limited ability to tolerate repeated macrostrain (+15% or more
the physiologic range for muscle).
Advantages: This is the simplest class of engineered muscle, typically involving the casting of
isolated myogenic precursor cells into a gel. It is still the most commonly employed method for
engineering muscle in culture, only because it is the easiest method to carry out with the resources
available in a typical molecular biology laboratory.
Disadvantages: These constructs in the current state of the art tend to have very weak
mechanical interfaces and are thus prone to damage at their points of attachment. In addition, the
cellular density in these constructs tends to be well below that of the other three classes, thus they
pose significant challenges when their performance is normalized by tissue volume for any
functional metric, including protein production, force generation, or sustained power output. To
date, these constructs have failed to perform adequately as mechanical actuators. Finally, the most
commonly used matrix materials inhibit myocyte fusion into myotubes, arresting the process of
muscle development and thereby limiting force and power output. The synthetic matrix materials
tend to mechanically fail (tensile failure at the tissue interface) within approximately 2 weeks in
culture, whereas self-organized engineered muscle (see below) will persist in culture for approxi-
mately 4 months, or longer.