**5. Hybrid scaffolds obtained by bioinspired assembling/mineralization process for bone and osteochondral regeneration**

Hard tissues are biological constructs incorporating minerals into soft matrix to create a protective shield or a structural support such as the bone, teeth, and cartilage [7]. The non-mineralized region, called also soft tissue, can be connective, muscular, nervous, or epithelial. Especially examining bone tissue, it is a highly dynamic and vascularized tissue which has an ability to self-heal and remodel through a well-orchestrated process; the bone remodeling is a constant process, targeting to replace odd bone through resorption by means of osteoclasts and to produce new bone by means of osteoblast which usually completes in 4–6 months. However, the high regenerative capacity is lost when there is a large segmental defect, severe non-unions, or bone tumor resection [66]. To overcome these issues, the concept of bone tissue engineering (BTE) has been developed producing

**41**

PO4

*Nature-Inspired Processes and Structures: New Paradigms to Develop Highly Bioactive Devices…*

tailor-made scaffolds with the ability to fine-tune the tissue regeneration process. Four different biological prerequisites are necessary for BTE such as osteogenic cells, osteoinductive stimulus, osteoconductive matrix scaffolds, and mechanical environment which led to design scaffolds with appropriate macroporous structure, good degradability, and better osteoconductive properties [67]. A 3D structure is not enough to obtain a material with osteoinductive stimulus, but the chemical composition plays a decisive role. Both concepts (chemical composition and 3D architecture) are at the basis of biomimicry; hence, to obtain scaffolds with chemical composition very close to natural bone, a bioinspired synthesis method mimick-

In this respect, previous studies by Tampieri et al. exploiting the biomineralization process abovementioned developed biocomposites made of collagen and

Exactly as it happens in nature, collagen molecules promoted complex 3D arrangement and the heterogeneous nucleation of a low crystalline hydroxyapatite also due to the incorporation of foreign ions, usually present in human tissue, into the apatite phase. In details, biomineralization process was reproduced in the labo-

an alkaline solution containing the Ca2+ ions exploiting a neutralization process. The pH of the suspension is increased up to neutral pH where two different mechanisms are simultaneously triggered; on the one hand, the collagen fibers reach the isoelectric point leading to their assembly into a 3D network; on the other hand, the mineral nucleation starts in correspondence to the carboxylic groups exposed by the collagen molecule that bind calcium ions [69–72]. One of the advantages of this material is the capability to entrap some foreign ions into HA lattice obtaining

a hybrid material mimicking natural mineralized tissues. In particular, CO3

can occupy two different sites of the apatite lattice. B-substitution occurs at the

<sup>3</sup><sup>−</sup> site improving the osteoblasts adhesion and is typical of young and immature bones; conversely, carbonation in site A refers to partial substitution of OH<sup>−</sup>, which increases the stability of mineral phase, and in fact it is more typical of mature bone tissue. Mg2+ promotes the HA nucleation and bioavailability decreasing the crystallinity. Sr2+ is able to restore the bone turnover balance; this is important for the

The aptitude of the apatite lattice to host several isovalent and heterovalent ion substitutions permits to synthesize apatite nanocrystals with multiple substitutions that can be used in different applications in regenerative medicine and nanomedicine. Furthermore, besides the incorporation of foreign ions, also the control mechanisms exerted by the organic phase allow to produce a more biomimetic apatite thanks to nearly amorphous crystal state and crystal orientation; in this way, cells well recognize hybrid composite without any inflammatory reaction and start to interact with it promoting the adhesion and proliferation on its fibers [75, 76]. Therefore, the use of bioinspired mineralization process is a tool able to confer unique properties to hydroxyapatite otherwise impossible to find in stoichiometric hydroxyapatite as well as in composites where hydroxyapatite was

Among bone defects, large chondral articular defects represent a major problem in orthopedic practice [77], and tissue engineering is providing promising results [78]. However, the results for the treatment of cartilage lesions are still controversial, and osteochondral lesions are even more severe relating to two different tissues featuring different self-healing abilities and cell lineages involved. 3D scaffold, usually, is able to well regenerate a single tissue, as cartilage tissue, and in case of osteochondral damage, additional autologous bone grafting is often necessary [79]. To overcome these limitations and to increase the advantages for osteochondral

<sup>3</sup><sup>−</sup> ions mixed with collagen gel into

<sup>2</sup><sup>−</sup> ions

ing the natural biomineralization process was carried out [68].

hydroxyapatite for bone and osteochondral regeneration [69–71].

ratory dropping an acid solution containing PO4

treatment of osteoporotic bone fractures [73, 74].

simply mixed with collagen [70].

*DOI: http://dx.doi.org/10.5772/intechopen.82740*
