Page 264 - Advances in Biomechanics and Tissue Regeneration
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13.4 MAGNETIC, MAGNETOMECHANIC, AND MAGNETOELECTRIC MATERIALS             261

           to their resemblance with the cellular membrane that allows better interaction with cells. Moreover, both nano-
           particles and liposomes are easily functionalized with other materials, allowing enhanced interactions and specific
           binding to the targeted biological entities, which ultimately imparts colloidal stability and biocompatibility [121].
           Also, one of the advantages of using magnetic nanomaterials in biomedicine is the fact that they are easily trace-
           able and localized inside the body through the action of a magnetic field, thus using minimally invasive
           methods [122].
              Magnetic nanomaterials may be divided, according to their morphology, in magnetic micro-/nanoparticles,
           which may be categorized into two different structures: pure metals (Co, Fe, Ni, and Ti) and metal oxides (iron
           oxides Fe 2 O 3 or Fe 3 O 4 and ferrites such as BaFe 12 O 19 and CoFe 2 O 4 ) and magnetic nanocomposites [123, 124].Mag-
           netic nanoparticles have been commonly used in a variety of cells and tissues for tissue engineering applications
           [125]. Also, they have been playing an important role in cell separation and immunoassays, drug targeting and
           delivery, gene delivery and transfection [126], and magnetic resonance imaging (MRI) contrast agents [127, 128].
           These particles vary in size, surface chemistry, magnetic properties, and bulk chemistry and often consist of a
           magnetic iron oxide core coated with a biocompatible polymer. This allows their functionalization enabling them
           to attach binding molecules such as antibodies, peptides, and other functional groups [129]. Magnetic nanopar-
           ticles may be attached to functional sites, such as the cell membrane and/or on internal cellular components, thus
           acting as transducers of magnetic fields and enabling the noninvasive control of various cellular functions [57].
           Early findings have shown that by functionalizing magnetic microparticles with ligands able to attach on different
           receptors on the cell surface, it was possible to study the mechanical linkage between the cell membrane receptor
           and the cytoskeletal network [130]. Since then, basic scientific research has been conducted on a variety of cell
           types to evaluate the mechanotransduction phenomenon assisted by these particles and respective coatings
           [131–137].
              These types of magnetic nanoparticles may be incorporated as a filler to obtain composites with magnetoelectric
           properties. The obtained magnetic nanocomposites are a very interesting material since it allows to remotely
           mechanically and electrically stimulate tissues from outside of the human body [138, 139] and for specific cell cul-
           tures in bioreactors [140]. The possibility to remotely control tissue stimulation without the need of patient move-
           ment is certainly an innovative approach. As previously mentioned and depicted in Fig. 13.1BandC, the
           mechanical deformation induced by a magnetic field due to the magnetostriction or magnetic properties of one
           of the components of the composite results in an electrical polarization variation due to the piezoelectric effect
           of the other phase, allowing large magnetoelectric effects at room temperature [141, 142].Thus the magnetic
           actuation ability of the magnetoelectric composite allows the mechanical and electrical stimuli of neighboring
           cells [143].
              Two main types of polymer-based magnetoelectric composites can be found in the literature: laminated composites
           and particulate micro- and nanocomposites [143]. Examples of that are the P(VDF-TrFE)/Metglas 2605SA1 laminates
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           that possess high magnetoelectric response (383V/cmOe ) [144] and P(VDF-TrFE)/CoFe 2 O 4 nanocomposites that
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           show lower magnetoelectric response (42mV/cmOe ) but present higher flexibility, simple fabrication, easy shaping,
           the possibilities of miniaturization, and the absence of degradation at the piezoelectric/magnetostrictive interface
           [145]. This is not the only advantages of nanocomposites; they also allow the development of geometries suitable
           for tissue engineering, namely, spheres [141] and fiber mats [146], which may be tuned for specific tissue engineering
           approaches.
              Therefore these composites, more precisely magnetoelectric biomaterials, have begun to be used as novel
           approach for tissue engineering applications and have already demonstrated to promote the cell prolifera-
           tion of preosteoblast cells by the application of a varying magnetic field [46, 147]. With these kinds of
           biomaterials, it is possible to provide mechanical or mechanoelectric stimulus to deliver higher cell proliferation
           (Fig. 13.3).
              Static or alternating magnetic fields applied in some clinical studies have already been reported, inducing the inte-
           gration and regeneration of tissues into ceramics [148]. Collagen magnetic scaffolds, which were fixed with external
           magnets in vivo, were also proven to induce controlled regeneration of bone cells [149, 150].
              Therefore tissue engineering approaches using mechanoelectric, magnetic, and magnetoelectric composites hold
           great promise, since it actively responds to biomimetic stimuli that control processes of cell regeneration and
           homeostasis.









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