**Basic Science and Research**

**Chapter 7**

**Nature-Inspired Nanotechnology and Smart Magnetic Activation: Two Groundbreaking Approaches Toward a New Generation of Biomaterials for Hard Tissue Regeneration**

Simone Sprio, Monica Sandri, Michele Iafisco, Silvia Panseri, Monica Montesi, Andrea Ruffini, Alessio Adamiano, Alberto Ballardini and Anna Tampieri

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/63229

#### **Abstract**

Today, as the need of new regenerative solutions is steadily increasing, the demand for new bio-devices with smart functionality is pushing material scientists to develop new synthesis concepts. Indeed, the conventional approaches for biomaterials fail when it comes to generate nano-biocomposites with designed biomimetic composi‐ tion and hierarchically organized architecture mimicking biologically relevant tissue features. In this respect, an emerging concept in material science is to draw inspira‐ tion from natural processes and products, which we may consider as the most advanced examples of smart nanotechnology. Natural processes of supramolecular assembly and mineralization of organic macromolecules, known as biomineraliza‐ tion, generate complex hybrid 3D constructs that are the basis of skeletons, exoskele‐ tons, nacre and shells. On the other hand, natural structures such as woods and plants exhibit multi-scale hierarchic organization that is the source of smart and anisotropic mechanical properties associated with high porosity and lightness. The association of nature-inspired nano-technological products with smart functionalization can provide new advanced solutions to critical and still unmet clinical needs. In this respect, magnetic activation of biomaterials by the use of a recently developed biocompati‐ ble, resorbable magnetic apatite promises to represent a new safe and effective switching tool, enabling personalized applications in regenerative medicine and theranostics that so far were not feasible, due to the cytotoxicity of the currently used magnetic materials.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**Keywords:** bone regeneration, bioinspired materials, biomineralization, biomorphic transformation, magnetic activation

### **1. Introduction**

Materials science today is experiencing a paradigmatic change in the development of new smart devices for biomedical applications. Particularly, the regeneration of hard tissues (i.e. bone, cartilage, tooth) is one of the most demanding issues in medicine and requires smart devices showing high mimicry of the host tissues and ability to instruct and drive progen‐ itor cells to activate the regenerative cascade. Therefore, among the various approaches pursued so far for the synthesis of bone biomaterials, wide consensus is now consolidated around the concept of "*biomimetics*". Such a definition indicates the ability of a synthetic material to closely reproduce the chemical composition, physical properties, and architec‐ ture of native tissues, with the purpose to create 3-D environments able to deliver signals stimulating cell chemotaxis and specific differentiation of autologous stem cells [1]. In this way, the main concept is that bone regeneration can be greatly aided by the fact that, by implantation of a biomimetic scaffold, the patient body acts as a natural bioreactor guid‐ ing proper tissue regeneration without the need of complicated tissue engineering proce‐ dures or of the use of biological factors, thus improving the safety of clinical approaches.

In this respect the chapter highlights some emerging concepts related to the development of bio-inspired materials addressed to hard tissue regeneration. In particular, the focus is on assembling/mineralization techniques that reproduce the cascade of phenomena acting in the formation of hybrid nanocomposites such as bone and shells, that can generate hybrid fibrous structures with excellent regenerative ability. This process, pinning on the exchange of information stored in the structure of natural polymers, is characterized by great versatility that enable the synthesis of smart multifunctional scaffolds for regeneration of tissue com‐ plexes such as joints and periodontium.

On the other side, the chapter is focused on the emerging concept of biomorphic transforma‐ tions by which natural structures with hierarchic architecture are converted into apatitic biomaterials with unpreceded bioactivity and structure, by multi-step chemical processes. In fact, as the process bases on heterogeneous reactions at the interface between a solid template and a gaseous phase, the obtained scaffolds result well consolidated without the need of sintering treatments and exhibit enhanced mechanical properties, due to the hierarchical architecture, thus being very promising for regeneration of load-bearing bones such as those of the limbs. Finally, the chapter highlights the recent development of an iron-substituted hydroxyapatite (HA) nanophase that, thanks to its excellent biocompatibility and intrinsic magnetic properties, demonstrated ability to be activated by remote magnetic signalling, thus representing a new switching tool for the development of a multifunctional platform gener‐ ating smart bio-devices for various applications in regenerative medicine and theranostics. This new material, overcoming the limitations of toxic iron oxide nanoparticles currently used in nanomedicine, is very promising for the future establishment of new and more effective and personalized approaches for bone regeneration and cancer therapies. Moreover, the possibility of boosting bone regeneration by magnetic stimulation in patients with reduced endogenous potential is a key issue, in consideration of the progressive ageing of the population for which more effective and personalized regenerative therapies will be increasingly demanded in the incoming decades.
