2.2.10. Magnetic Nanoparticles

Magnetic elements (i.e., iron, nickel, cobalt, and their oxides) were utilized for the fabrication of nanomaterials for different medical applications [429,430] such as MRI, drug delivery, medical diagnostics, cancer therapy, biosensoring, and magneto-optic devices. Magnetic nanoparticles can be synthesized through different techniques including co-precipitation [431], microemulsion [432], hydrothermal synthesis [433], sol–gel process [434], polyol synthesis [435], flow injection [436], sonolysis/sonochemical methods [437], microwave irradiation [438], electrochemical synthesis [439], solvothermal method [440], chemical vapor deposition [441], laser pyrolysis [442], and green synthesis [443] using biomass or biotemplate.

Due to high magnetic flux density, magnetic nanoparticles were used for drug targeting [444] and bio-separation [445], including cell sorting [446]. Sun et al. [447] analyzed metallic, bi-metallic, magnetic cationic liposomes and superparamagnetic iron oxide nanoparticles for imaging and drug delivery. The surface of magnetic nanoparticles also needs to be functionalized to recognize specific targets (Figure 21) [448]. Polyethylene glycol (PEG) is one of the best polymers used for the functionalization of magnetic nanoparticles by surface modification [449]. Interestingly, surface modified magnetic nanoparticles reduce nonspecific interaction with biological molecules.

**Figure 21.** Surface modified magnetic nanoparticle.

Magnetic manipulation is another important advantage of magnetic nanoparticles [450]. It is done by labeling cells with magnetic nanoparticles that can easily be controlled by remote control or external magnetic field [451]. The magnetic nanoparticles, which are usually smaller than 10 nm can be easily transported through skin lipid matrix and hair follicles to the stratum granulosum, where it is condensing between corneocytes [452].

In orthopedic surgery, implant-associated infection is a serious issue, as stated in the previous sections. Infection around a bone graft can lead to serious illness or failure of surgery. Drug-loaded Fe3O4 composites promote cell adhesion, proliferation, and osteogenic differentiation of hBMSCs [453–455]. In stem cell therapy for bone regeneration, an application of these NPs is the magnetic targeting of stem cells to the deserved locations, known as magnetic homing of stem cells. For example, penetration of ferumoxide-labeled cells into porous hydroxyapatite ceramic implanted in a rabbit ulnar defect was significantly facilitated by this approach, which improved bone formation even in the chronic process [456].

2.2.11. Summary and Statistical Analysis of the Survey on Inorganic Nanobiomaterials

The survey on inorganic nanobiomaterials presented in Section 2.2 covered some 230 articles, practically the same as its counterpart for organic biomaterials not counting about 30 articles on fabrication techniques of silica and magnetic nanoparticles.

While the number of technical papers appears to be rather uniformly distributed among the ten types of inorganic nanomaterials considered in this survey, it should be noted that most studies focused on nanoparticles and their functionalization for drug/gene/therapy delivery, cell labeling, biosensing, and bioimaging (75%), followed by studies on development and fabrication of new composite materials and scaffolds (25%).

Gold and titania present the largest variety of nanostructures and the latter material may also be available in the form of nanotubes. Gold nanoparticles may represent the best solution for most applications in view of the possibility of controlling size and dimensions of nanostructures as well as for their special physical properties (for example, local plasmon resonance). However, massive utilization of GNPs is obviously limited by the high cost of gold. Silica and titania nanoparticles also are widely utilized as standalone materials or in combination with gold and silver nanoparticles.

Similar to what has been observed for organic nanobiomaterials, a rapidly growing research area in the field of inorganic nanobiomaterials for bone tissue engineering is to hybridize them with other materials (e.g., chitosan, PLA, PLGA, collagen, and hydroxyapatite) to enhance mechanical properties, biocompatibility and osteogenetic properties of the modified materials. Development of high-performance scaffolds comprised of multiple materials is the final stage of this complicated process.
