*4.4. Composites with Titanates*

Titanium and its alloys have been used in combination with calcium phosphates for bone tissue engineering due to their excellent mechanical properties [196]. Metallic prostheses and implants are widely used to replace damaged bones and teeth, and their interaction with the surrounding tissue depends on the chemistry and microstructure of the surface [197], but their main drawback is related to their poor bioresorbability. In this respect, the preparation of bioceramic composites containing titanium oxides was considered as a valuable approach, exhibiting good biocompatibility and enhancing in vivo osteointegration [198,199].

Titanium oxide nanomaterials can also be added to injectable cements and pastes, leading to higher injectability and improved mechanical performance [175].

Some titanates, such as barium titanate (BaTiO3, BT) and strontium titanate (SrTiO3), are also characterized by piezoelectric properties, potentially providing microstructural accumulation of charges mimicking the mechanotransduction of bone cells [183,184,200,201]. BT-HA composites were investigated to combine the bioactivity of HA with the piezoelectricity of BT [184,200]. Three-dimensional-printed highly porous piezoelectric scaffolds based on BT and HA were obtained, with good cytocompatibility and cell attachment [184]. An aligned porous BT-HA piezoelectric composite was obtained by the ice-template method, exhibiting high porosity, cell proliferation, differentiation and adhesion of osteoblastic cells [200].

#### **5. Conclusions**

Calcium phosphates are widely accepted biomaterials and the gold standard to promote the regeneration of bone tissue. CaP scaffolds with biomimetic composition can exhibit osteogenic ability, bioresorbability and antibacterial properties. However, appropriate mechanical properties are required if the target is the regeneration of critical-sized bone defects, particularly when load bearing.

The co-existence of various factors, such as bioactive chemical composition, nanostructure and bone-like mechanical performance, is a major problem with ceramics due to the need of sintering and the difficulty of achieving complex bone-mimicking 3D structures. In fact, several technologies developed in the last decades for the manufacturing of a highly porous bioceramic-based scaffold from traditional methods (partial sintering, replica method, sacrificial template and direct foaming, as well as various 3D printing technologies) usually fail in generating bioactive and effective bone scaffolds. Hence, future perspectives are strongly related to the development of new approaches that can generate bone scaffolds endowed with bone-mimicking features yielding effective regenerative ability. To this end, recently developed innovative approaches targeting low-temperature processes, including chemically induced consolidation of CaP pastes or biomorphic transformation processes, are examples of radically new methods enabling the possibility to create scaffolds retaining nanocrystallinity and bioactive, ion-doped composition or even multi-scale hierarchically organized architectures inherited from natural sources. These

results open new perspectives in ceramic science and are encouraging for further research in the field, targeting the decisive resolution of many still unmet clinical problems related to bone regeneration.

**Author Contributions:** Conceptualization, S.S., A.T. and M.D.; methodology, S.S., A.T. and M.D.; writing—original draft preparation, M.T.; writing—review and editing, M.D.; supervision, M.D. and S.S.; All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**

