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376 Biomimetics: Biologically Inspired Technologies

mechanical strength or are unable to hold a load. A greater degree of cross-linking would improve
response time and mechanical strength but result in reducing the extent of deformation. Develop-
ment of copolymer gels made of cross-linked hydrogels have resulted in actuators with improved
response time and good mechanical properties (Galaev and Mattiason, 1999). Cross-linked hydro-
gel actuators undergo linear contraction and expansion without volume change, and show faster
response time and improved mechanical strength compared to the individual components (Calvert
and Liu, 1999). Gels require an aqueous environment for operation, so a sealed environment or
coating is required for ‘‘dry’’ operation. Hydrogel actuators are light, compact, and flexible.
A natural polymer hydrogel made of a semi-interpenetrating polymer network (semiIPN) composed
of glutaraldehyde cross-linked chitosan and interpenetrating silk fibroin has demonstrated
reversible swelling–shrinking behavior and may have applications as an artificial muscle (Chen
et al., 1997).
An emerging area of research has been the development of ‘‘molecular actuators,’’ molecules, or
molecular assemblies that undergo conformational change in response to stimuli and perform work.
Rotaxane is a molecular system that consists of a ring threaded on a rod-like structure with blocking
elements at the ends. The ring shuttles along the rod between two points and can be driven by
chemical, photochemical, or electrochemical forces. A multicomponent rotaxane system consisting
of two string and ring units threaded together that contracts and stretches in response to a metal
exchange reaction has been developed (Collin et al., 2001). The string contains both bidentate and
terdentate ligands and the ring contains a bidentate ligand. This synthetic molecular muscle unit
adopts a stretched conformation in the presence of copper ions, which prefer to bind to two
bidentate ligands. Zinc ions prefer binding to a bidentate and terdentate ligand. When zinc ions
replace the copper, the rings slide along the string from the bidentate ligand to the terdentate ligand,
resulting in a contracted conformation. This synthetic molecule replicates the sliding motion of
natural muscle actin and myosin filaments.
In addition to the synthetic replication of molecular motors, there has been research into
developing actuators using natural proteins. An artificial muscle from real muscle components
has been synthesized in vitro (Kakugo et al., 2002). Isolated myosin molecules cross-linked under
stretching showed self-organization capabilities and orientated to form hierarchical structures.
ATPase activity comparable to native myosin was seen in the presence of actin and addition of
ATP resulted in the motion of F-actin along the axis of oriented myosin gel. Actin gels formed from
cross-linked actin–polymer complexes also showed preferential motility on the orientated myosin
gel in the presence of ATP. NonATP based molecular motors have been isolated from sieve
elements of legumes (Knoblauch et al., 2003). The crystalloid protein bodies, dubbed forisomes,
are part of the microfluidic system for transport of water and minerals throughout the plant.
Forisomes have a disordered (extended) shape in the absence of calcium ions. In the presence of
calcium ions forisomes take on an ordered (swollen) conformation, acting as a cellular stopcock to
block fluid flow. Isolated forisomes were observed to swell radially and contract longitudinally in
the presence of calcium ions. This anisotropic deformation response was reversible in the absence
of calcium ions and multiple expansion–contraction cycles were induced without causing a
decrease in responsiveness.
Tissue engineering is a means of creating a biological substitute that is capable of restoring,
maintaining, and improving function. Smooth muscle tissue has been successfully engineered
in vitro on tubular scaffolds of poly(lactic-glycolic acid) seeded with bone marrow derived
mesenchymal stem cells (Cho et al., 2004). The differentiated cells exhibited smooth muscle-like
morphology and expressed smooth muscle cell specific markers, SM a-actin and SM myosin heavy
chain. Bone marrow cells also have the capacity to differentiate into cardiac tissue both in vivo and
in vitro. Stem cells injected into the myocardium develop a cardiomyogenic phenotype and BMSC
transplant experiments have been shown to be effective in treating infarcted myocardium
by generating de novo myocardium (Orlic et al., 2001). Differentiation of stem cells treated with
5-azacytidine, a cytosine analog, that regulates differentiation into cardiomyocytes has also been