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                       Potential applications: Drug delivery when used as an implanted device, in vitro model for
                    basic research in cultured muscle cells.

                    9.3.1.4 Self-Organized Muscle Tissue Engineered In Vitro

                    Isolated myogenic cells are cultured under conditions to provide cues that promote self-assembly of
                    the cells into functional three-dimensional (3-D) tissues.
                       Advantages: Self-organizing muscle tissues can take full advantage of genetic engineering
                    combined with the inherent phenotypic potential of all muscle tissues. Thus, a virtually limitless
                    range of tissue architectures are possible. In principle, any myogenic cell type from any species can
                    be employed. The authors (Dennis et al.) have successfully engineered skeletal and cardiac
                    precursor cells into functional 3-D tissues in culture from a range of animal species.
                       Disadvantages: The cells within the tissues tend to remain at an arrested stage of development
                    (neonatal phenotype), exhibiting low levels of contractility and excitability. The mechanical and
                    chemical environment during development must be emulated in order to promote the formation of
                    adequate tissue interfaces.
                       Potential applications: With appropriately engineered tissue interfaces and the application of
                    the correct external signals, self-organized muscle actuators can be used in any application for
                    which muscle tissue is needed. This is the most general form of engineered muscle, and has the
                    greatest ultimate potential for many applications. Correspondingly, this class of actuators presents
                    the greatest number of technical challenges.


                          9.4  BIOMECHATRONICS: WHY USE LIVING MUSCLE IN MACHINES?


                    The ability to engineer muscle actuators may have significant impact on many areas including: (1)
                    drug testing and screening in in vitro bioreactors, (2) drug delivery when implanted as a living
                    ‘‘protein factory,’’ (3) the ability to construct practical hybrid mechanical actuators and robotic
                    devices using both motile cells and self-organized tissues, (4) the ability to build biohybrid
                    prosthetic devices, (5) engineered tissue for surgical transplantation, including both skeletal
                    muscle (~45% of adult human body mass) and cardiac, (6) the ability to harvest high-quality
                    animal protein for food from a controlled bioreactor environment. The importance of the last
                    application becomes clear in light of recent concerns about prion disease, a growing social pressure
                    to reduce animal suffering, and the need for closed ecosystems for long-duration space flight and
                    exploration.
                       The focus of this chapter is the use of living muscle as a mechanical actuator in engineered
                    systems. The main reason that living muscle is seriously considered for such use is simply because
                    the performance of muscle tissue as an actuator is generally quite favorable when quantitatively
                    compared with synthetic actuator technologies. Direct quantitative functional metrics of various
                    mechanical actuator systems, including muscle, have been reviewed in detail by Hollerbach et al.
                    (1991). The benchmark for most of the synthetic muscle actuator systems currently under devel-
                    opment is living muscle. Muscle has considerable advantages over many synthetic actuator
                    technologies both in terms of quantifiable FoM, as well as in terms of many qualitative features
                    unique to living muscle. The potential qualitative advantages of muscle are many: muscle operates
                    almost silently, generates biodegradable substances when converting fuel to mechanical work, can
                    functionally adapt to changing demands, and can take many forms and sizes unlike any traditional
                    synthetic actuator technology. The potential quantitative advantages of living muscle as a mech-
                    anical actuator are principally the high-chemomechanical efficiency when operating at nearly room
                    temperature, and the high power density with peak values ranging from 50 to 150 W/kg, depending
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