3.1.1. Calcium Phosphate, Hydroxyapatite, and β-Tricalcium Phosphate

CaP belongs to the family of minerals containing calcium cations (Ca2+) together with inorganic phosphate anions, which are abundant in native human bone and teeth [53]. CaP is a representative bioactive material [53]. The calcium ion induces the proliferation and differentiation of human mesenchymal stem cells (MSCs), stimulates osteoblastic bone synthesis by activating the extracellular signal-regulated kinase 1/2 pathway and phosphatidylinositol 3-kinase/Akt pathways [53–56]. In addition, phosphate regulates the proliferation and differentiation of the osteoblasts and increases the expression of BMPs [53,57,58]. CaP demonstrates osteoconductivity and osteoinductivity characteristics through the above cell signaling pathways as well as good biocompatibility, nonimmunogenicity, and non-inflammatory behavior [59]. CaP has been utilized to improve bone regeneration in ways such as increasing osteoconductivity for bone ingrowth, enhancing osteoinductivity for bone mineralization with ion release control, and encapsulating drugs or growth factors [59,60]. Hydroxyapatite (HA, (Ca5(PO4)3(OH))) and β-tricalcium phosphate (TCP, (Ca3(PO4)2)) are also included in this family [53]. HA constitutes the largest amount of inorganic components in human bone [61]. Calcium phosphate has been

studied for bone regenerative treatment as a coating material for membrane and dental implants, and also as a raw material [53].

In 2017, Chu et al. studied nanostructured HA (nanoHA)-coated epigallocatechin-3 gallate (EGCG) cross-linked collagen membranes [14]. In this in vivo study, nanoHA-coated and EGCG cross-linked collagen membranes showed the highest bone healing efficacy [14]. Furthermore, due to EGCG, the membrane showed improved mechanical properties, such as elasticity and thermal stability [14]. In 2019, Nguyen et al. studied strontium (Sr) doped CaP-coated Ti mesh membranes. Both Sr- and CaP-coated Ti mesh presented the highest percentages of bone–mesh contact in the critical bone defect animal model [23]. In 2019, Higuchi et al. used electrospraying or sonocoating methods for nanoHA coating of Poly(D,L-lactic acid), (PDLLA)/Poly(D,L-lactide-co-glycolide) (PLGA) membranes. In this study, nanoHA sonocoated polymer membranes showed better cellular metabolic activity than non-coated control membranes [18].
