Page 257 - Advances in Biomechanics and Tissue Regeneration

254 13. MULTIDIMENSIONAL BIOMECHANICS APPROACHES

13.1.1 Bone
Yasuda et al. were the first to report the piezoelectric effect in dry bones [13, 14]. This effect can be also found in other
tissues such as tendon, ligaments, cartilage, skin, dentin, collagen, deoxyribonucleic acids (DNA), and cell membranes
[5, 15–17].
Bones consists of a solid matrix and a fluid phase containing blood and extracellular fluid. The solid phase is com-
posed by a crystalline mineral phase (calcium, phosphate, and carbonate), an amorphous mineral phase, collagen
fibers, and a ground substance [3]. Thus bone consists mainly of three phases: collagen (which is piezoelectric), extra-
cellular minerals, and pores. Typically a mechanical stress induces a polarization variation, and the application of an
electric field produces the converse effect, a change in the material geometry or strain. The electroactive properties stem
from the crystalline nature of collagen, and the displacement of hydrogen bonds in these crystals. Apparently, when
the fiber is hydrated, the crystalline structure of collagen also changes, and the bound water favors a change in the
crystal symmetry, reducing the piezoelectric properties [18, 19]. The piezoelectric response of human bone was quan-
tified by means of a piezoresponse force microscope resulting to be 7–8 pCN 1 [20].
Bone tissue shows a large potential to repair and regenerate itself through complex feedback mechanisms, where
electromechanical processes are essential due to its piezoelectric nature. The first report by Yasuda et al. was later ver-
ified after the observation of electrical variations and electric potential regeneration when the bone is mechanically
stressed [14, 21]. As a consequence of these mechanical stresses, electrical signals are produced and stimulate bone
growth and remodeling [22]. Osteocytes, which play an important role in the structural regeneration of bone and bone
mechanotransduction, seem to be the responsible for bone growth under piezoelectric signals [23, 24]. Then, these cells
communicate with other cells, such as osteoblasts and osteoclasts for bone regeneration.
The enhancement and stimulation of osteogenic activities after the application of electrical stimulation has been
demonstrated. Thus osteoblasts are affected by electromechanical signals, and, due to the piezoelectric nature of bone,
the mechanical stimuli are converted into electrical [25, 26]. Moreover, under dynamic mechanical conditions, the
growth and differentiation of osteoblasts in a piezoelectric material can be enhanced.

13.1.2 Collagen and Other Piezoelectric Tissues
Other tissues containing collagen, such as tendons and ligaments, also display piezoelectricity and, thus, undergo
an electrical potential variation when a mechanical stress is applied [27, 28]. The piezoelectricity of dry tendons has
been measured resulting in a decrease of the piezoelectric coefficient as hydration increases [19, 29–31]. Other soft tis-
sues, such as skin, callus, cartilage, and tendons seem to be related with the orientation of the protein fibers [15, 32].
Fibrous molecules such as collagen, keratin, fibrin, elastin, or cellulose, present in connective tissues, show also pie-
zoelectric properties. Electrical polarization variations were also verified in hair [33] when subjected to stress and in
DNA [27]. Pineal gland tissues also contain noncentrosymmetric material, which is also piezoelectric [34].

13.1.3 Cardiac Tissue

The myocardium is a highly organized structure with unique electrical and mechanical properties. Thus cardiomyo-
cyte growth and maturation seem to be influenced by mechanical loading and electric fields. Some heart characteristics
such as size and performance can be guided by these stimuli. The myocardium is formed by fibers with a multilayered
helical architecture essential for heart contraction for which mechanical stretching and electrical current stimulation
are essential for the development of the tissue. Apparently, when mechanical and electrical stimuli are combined, they
are able to promote contractility, calcium handling, protein expression, or cell proliferation [35, 36]. Combined
mechanical and electrical stimulations proved to influence also recellularization, cardiomyocyte differentiation,
and tissue remodeling in 2–4days [37]. Electric fields also increase the mitochondrial content, influencing the conduc-
tion velocity, cell orientation, and contractile force. On the other hand, mechanical stimuli induce chemical and elec-
trical responses in cardiomyocytes. The use of mechanical stretches between 10% and 15% proved to improve cardiac
tissue structure and force development [38].

13.1.4 Nerve Tissues

Neurons transmit electrochemical signals across the nervous system. Thus they are affected by electrical stimuli [4].
The information is sent by axons, and their activity is associated to electrical variations. If an electric current goes
through the neuron’s membrane, it results in an action potential. Under an appropriate stimulus the cell membrane

II. MECHANOBIOLOGY AND TISSUE REGENERATION