*4.2. Composites with Silicates*

The preparation of composites containing both calcium phosphates and silicates has been explored with several approaches for the purpose of enhancing the mechanical properties of scaffolds. In fact, various studies showed that calcium phosphate composites with calcium silicates exhibited enhanced compressive and flexural strength [172,173].

Si-containing bioceramics include colloidal silica nanoparticles [174,175], silicates (i.e., calcium silicates and zinc silicates) [176–178], glasses [179,180] and silicate-phosphates (i.e., silicocarnotite and nagelschmidtite) [181,182]. Regarding the preparation of bone cements, previous studies showed that the addition of silica nanoparticles led to a decrease in the setting times and led to improved mechanical properties, especially due to the formation of Si-O-Si bonds among the particles [174,175]. Calcium phosphate cements containing zinc silicate and PLGA microspheres were also prepared [162]: the role of Si and Zn in improving setting times, injectability and compression strength was observed, while the addition of the microspheres did not affect the porosity.

The incorporation of silicates becomes particularly interesting in bioglass-reinforced cements, e.g., single-phase crystalline or amorphous calcium silicate phosphates (CaO-SiO2- P2O5, CaSiP) or Bioglass A5S4, resulting in increased setting times and injectability [179,180]. The incorporation of bioglasses also significantly improved the bioactivity of the scaffold, promoting osteoblast attachment, proliferation and differentiation in vivo. The effect of CaSiP (silicocarnotite, Ca5(PO4)2SiO4) in brushite cements was also investigated, showing the role of Si in favoring the formation of HA, osteoblast proliferation and the formation of novel bone tissue [181].

The application of single-phase calcium phosphate silicate bioceramics (CaSiP) is not limited to bone regeneration but also to periodontal repair. In this respect, various works showed the preparation of 3D-printed silicate bioceramics, such as nagelschmidtite (Ca7(SiO4)3(PO4)2, CSP) and silicocarnotite (Ca5(PO4)2SiO4, Sss) [48]. CaSiP showed good biological performance with the formation of flake-like apatite layers (in the cases of Sss and CSP, respectively). The ion release positively induced cell proliferation and differentiation as well as the formation of the extracellular matrix and the mineralization of periodontal tissue [183,184].

#### *4.3. Composites with Carbon*

The interest in the synthesis of composites with calcium phosphates and carbonderived structures rapidly rose in recent years, especially considering graphene, a 2D material made of nanosheets of hexagonally bonded carbon atoms characterized by a high surface area, high conductivity, excellent mechanical properties and good biocompatibility, particularly interesting for tissue engineering applications [185–187].

The synthesis strategies to obtain graphene/carbon nanotubes–hydroxyapatite composites have been reported, evidencing hemocompatibility, antibacterial properties and the ability of graphene–hydroxyapatite composites to increase osteogenic activity [161,163,188–194].

A hybrid composite made of graphene oxide (GO), chitosan (CS) and HA (GO-CS-HA) was developed as a coating for titanium implants, exhibiting an increased formation of biomimetic apatite and also antibacterial properties, possibly ascribed to the increased production of reactive oxygen species [177].

Furthermore, 3D-printed composite scaffolds made of β-TCP, reduced graphene oxide (RGO), magnesium nanoparticles and arginine were prepared [176]. The combination of amino groups of arginine, released Mg ions and the nanotopography of GO resulted in increased mechanical performance.

The effect of RGO and carbon nanotubes (CNT) in α-TCP-based cements was evaluated. The setting times decreased when increasing the concentration of RGO, while negligible variations were observed with the addition of CNT; the mechanical performance was also valuable for load-bearing applications [178,195].

The use of microwaves resulted in a reduction in setting time and an increase in mechanical properties, ascribed to the evaporation of gas from the surface of RGO and CNT, strengthening the final composite [195]. The formation of an external HA layer was observed, favoring cell adhesion and proliferation.
