## 4 Discussion
### In Vitro Studies  
Several studies observed that strontium-doped biomaterials significantly improved osteogenic differentiation and biocompatibility. For instance, [PERSON] et al. [50] found that air-plasma-treated titanium alloy coatings with strontium-doped phosphate significantly improved osteogenic differentiation and biocompatibility. Similarly, [PERSON] et al. [20] showed that strontium-doped mesoporous bioactive glass scaffolds significantly promoted osteoblast differentiation and angiogenesis, suggesting their potential for enhancing bone regeneration through dual osteogenic and angiogenic effects. [PERSON] et al. [21] observed that strontium-substituted hydroxyapatite coatings on polyetheretherketone (PEEK) significantly enhanced the proliferation and osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs), highlighting their potential for improving the biological performance of orthopedic implants. In addition, [PERSON] et al. [36] demonstrated that strontium-substituted hydroxyapatite coatings significantly enhanced osteogenic differentiation and mineralization in mesenchymal stem cells, emphasizing the need for precise control over strontium concentration to optimize cellular responses. [PERSON] et al. [37] confirmed that strontium-substituted hydroxyapatite coatings significantly improved the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), highlighting the potential of strontium-doped biomaterials for enhancing bone regeneration in vitro. Other studies confirmed interesting effects in different types of Sr-doped calcium phosphates. [PERSON] et al. [42] found that the Sr-doped hydroxyapatite derived from Mercenaria clam shells not only improved mechanical properties but also enhanced osteoblast proliferation and differentiation, demonstrating excellent in vitro biocompatibility and potential for bone tissue engineering. [PERSON] et al. [39] observed that titanium substrates coated with strontium-doped calcium phosphate ceramics exhibited enhanced cell adhesion and proliferation, emphasizing the importance of optimizing the strontium doping concentration. [PERSON] et al. [31] showed that strontium-doped hydroxyapatite bioceramics with micro-nano-hybrid surfaces significantly promoted the proliferation, differentiation, and angiogenic activity of bone marrow stromal cells (BMSCs), highlighting the synergistic effects of surface modification and strontium doping. [PERSON] et al. [33] demonstrated that strontium-doped hydroxyapatite coatings on titanium substrates significantly enhanced the proliferation and osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs), suggesting their potential for improving bone regeneration in vitro. [PERSON] et al. [26] observed that strontium-doped bioceramics significantly enhanced the expression of osteogenic markers and promoted bone regeneration in vitro, indicating their potential for improving the biological performance of biomaterials for bone repair applications. [PERSON] et al. [46] developed a novel fast-setting strontium-containing hydroxyapatite bone cement with a simple binary powder system. This new Sr-CPC displayed excellent compressive strength and favorable cytocompatibility, highlighting its potential for clinical applications in bone tissue repair. [PERSON] et al. [45] further demonstrated that Sr-functionalized hydroxyapatite nanoparticles enhanced collagen I, osteocalcin expression and alkaline phosphatase activity in osteoblasts, indicating their potential to boost bone formation through improved cellular activities. Although many papers present a large panel of in vitro tests covering several important aspects of understanding the bone formation process, the focus on certain markers, such as ALP, underscores their significance in evaluating osteogenic activity. While most in vitro studies in this review concluded that the presence of strontium associated with the biomaterial increased the expression/activity of ALP, [PERSON] et al.