**4. Injectable self-hardening bone cements with biomimetic composition and nanostructure**

Bone diseases, such as hemangioma, multiple myeloma, osteolytic metastases, and osteoporosis, can yield bone weakening, thus commonly resulting in fractures in the vertebrae, femur, and radius, especially in the elderly [43]. Minimally invasive surgery procedures, such as vertebroplasty and kyphoplasty, are currently used to regenerate osteoporotic fractures with bone cements as bone defect fillers [44].

Ideally, bone cements should exhibit adequate mechanical support to withstand the early biomechanical loads and should establish effective integration with newly formed bone. The most common injectable cements are based on polymethyl methacrylate (PMMA), thanks to their favorable mechanical properties and robustness [45]. However, PMMA bone cements lack the necessary bioactivity and resorbability, for which it is a foreign body presenting excessive rigidity, in comparison with the bone, so to potentially provoke secondary fractures at adjacent vertebrae. Moreover, PMMA hardening occurs through an exothermic polymerization process, leading to the risk of thermal necrosis of the surrounding bone tissue [46]. In contrast with these drawbacks, calcium phosphate-based bone cements (CPCs) have attracted great attention due to their excellent bioactivity, deriving from the chemical similarity with the bone tissue, and bioresorbability, which lead to the formation of new bone that can replace the implant [47, 48].

Numerous CPC formulations with different initial reactants (which include α-tricalcium phosphate, β-tricalcium phosphate, anhydrous dicalcium phosphate, and monocalcium phosphate monohydrate), producing either an apatitebased or brushite-based cement [49], have been reported [50, 51]. In addition to their excellent biological behavior, CPCs are intrinsically microporous: pores in the size range of submicro-/micrometers are left by extra aqueous solution after hardening of CPCs [52]; such micropores are effective for the impregnation of biological fluids into the bone cements and help resorption and replacement of implants by bone.

**39**

microstructure [65].

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

One of the most critical issues of injectable CPCs is the control of the chemistry of setting reactions and rheological properties, to achieve adequate injectability, setting time, and mechanical properties [53]. A recent interesting approach involves the addition of natural polymers or their derivatives, such as sodium alginate [54], hydroxypropyl methylcellulose [55], hyaluronic acid [56], chitosan [57], and modified starch [58], into the starting powder or in solution into the cement paste [59]. Biopolymers can be developed as low-viscosity solutions for easy injection and have the ability to cross-link in situ after injection under physiological conditions (temperature or pH) or by the action of an initiator (light or cationic cross-linkers) [53]. In general, due to the higher viscosity of the CPC paste, the presence of polymers tends to increase setting time and to enhance CPC injectability and cohesion. Furthermore, the use of biopolymeric additives can be an effective method to improve the mechanical performance of CPCs [53]. Depending on the final CPC properties desired, different polymers may be incorporated into CPCs, and the polymeric solution may be altered by changing concentration, molecular weight,

Among the several approaches proposed for the synthesis of CPCs, the use of α-tricalcium phosphate (α-TCP) powder [60] as a metastable precursor is particu-

Sr2+, enhancing bioactivity and providing efficient therapies against degenerative

In particular, CPC formulations based on Sr-doped apatitic cements are very interesting because of strontium ability to enhance cell proliferation and differentiation into bone-forming osteoblasts and decrease the resorbing activity of mature osteoclasts; this is a key achievement for the restoration of the bone turnover balance, especially when the cement is used to treat osteoporotic bone fractures [62]. Sr-substituted TCP was shown to slow down the cement setting as well as the transformation into Sr-doped HA. Moreover, due to apatite lattice expansion, the introduction of strontium in the apatite structure is associated with an increased solubility of the cements, leading to an increase of ions released, which in turn was found to have a positive effect on cell proliferation and osteogenic differentiation [62]. In particular, Sr-substituted CPCs previously tested in vivo exhibited increased new bone formation compared to Sr-free CPCs. Due to the different preparation routes and properties of the set samples, such as phase composition and porosity, contradicting results of Sr effect on the mechanical characteristics of substituted CPCs can be found. In most compositions setting into Sr-HA, strontium substitution either increased compressive strength or had no significant effect on

Recently, novel injectable, self-setting Sr-HA bone cements were prepared by mixing Sr-substituted α-TCP phases as unique inorganic precursors with disodium phosphate solutions enriched with alginate. In vitro tests showed that different concentrations of Sr2+ were able to promote an inductive effect on mesenchymal stem cell differentiation, especially at 2 mol% concentration, and on pre-osteoblast proliferation and an inhibitory effect on osteoclasts activity [64]. Moreover, the addition of alginate significantly improved both injectability and cohesion, leading also to significantly higher compression strength when compared with alginatefree cements, without affecting the hardening process and with the absence of cytotoxic effects. On the basis of these results, a selected Sr-HA cement formulation was further tested in vivo in a rabbit model by compositional, morphological, and histological/histomorphometric analysis. The cement exhibited complete transformation into HA, thus showing a biomimetic composition, and enhanced the ability to induce new bone formation and penetration, provided also by its porous

<sup>2</sup><sup>−</sup>, SiO4

<sup>4</sup><sup>−</sup>, and

larly of interest for introduction of foreign ions, such as Mg2+, CO3

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

and polymer chain length [59].

bone diseases [19, 20, 61].

the mechanical characteristics [63].
