**5. Conclusions and future perspectives**

nanoparticles can be easily incorporated into cells by endocytosis, thus obtaining "magnetic cells" without negatively affecting cell behavior (e.g. proliferation, morphology, differentia‐ tion). Through the application of an external magnetic field of low intensity, these cells can be guided within a scaffold, in order to have faster and more selective seeding for tissue engi‐

neering application (**Figure 11**).

142 Advanced Techniques in Bone Regeneration

**Figure 11.** Scheme of magnetic guiding enabling enhanced scaffold colonization.

to more advanced and personalized therapies.

Biocompatible magnetic media can also be associated to polymeric or hybrid carriers to achieve

Hollow micro- and nano-spheres with controlled size and magnetization level, made of polycaprolacton coated with adequate amounts of FeHA displayed dose-dependent biocom‐ patibility towards bone marrow mesenchymal stem cells, thus highlighting the positive effect of the mineralization extent on cell behaviour [78–80]. These carriers could be developed as magnetically-responsive drug delivery systems with activation and delivery kinetics modu‐ lated by phenomena of magnetoshaking or hyperthermia [81]. To explore these new ap‐ proaches for controlled drug delivery, careful investigation is needed to investigate the most suitable conditions, by means of intensity and frequency of alternated magnetic fields that shall provide the energy needed for the release of the linked bioactive molecules. Therefore, in the incoming years further development of this approach may represent a new tool enabling the release of different chemical species under defined temporo-spatial patterns, thus opening

new smart drug delivery systems with the ability of magnetic activation [72–77].

The incoming decades will experience a growing role of smart biomaterials in therapies for bone regeneration. In this respect, a significant effort to develop nature-inspired synthesis approaches will generate new scaffolds endowed with high mimicry of host tissues and smart functions that will greatly improve the existing therapies and, might also generate new ones that were prevented so far by the inadequateness of the existing biomaterials. On the basis of some existing examples of nature-inspired biomaterials showing effective regenerative ability, and on the increasing effort of material scientists in the synthesis of biomimetic devices, it can be envisaged that significant advances will be reached in the next decade. In this respect, new emerging concepts of fabrication, such as biomineralization or biomorphic transformation, will overcome the limitations of current manufacturing techniques that, particularly in the case of ceramics, are not able to provide highly organized structures with details defined at the micron size. In this respect, due to the innumerable examples of natural structures exhibiting smart properties that are not achievable by conventional fabrication approaches, there are virtually no limits to the potential applications of biomorphic materials in various high-impact fields other than the biomedical one. Besides, the attainment of smart functionalization is another key topic that is engaging a significant part of the biomaterials researchers, particularly due to the increasing need to overcome the systemic drug administration and to provide more effectiveness and targeting to the existing therapies. In this respect, as safety, effectiveness, and targeting are key objectives for real applicability in nanomedicine, the use of magnetic stimulation can be considered as a promising concept that is raising ever increasing interest among scientists and will probably experience extended diffusion in the incoming years.
