## 4 Discussion
### Involvement of Signaling Pathways  
Smart materials can promote tissue support while stimulating beneficial responses such as lesion regeneration or infection reduction by activating or inhibiting several path ways and processes at the cellular level [73]. Understanding which intracellular signaling pathways are activated after contact with a strontium-functionalized ceramic biomaterial can help predict the behavior of the cell in response to the implant and, therefore, is an efficient way to understand how doping with strontium can help in the development of more efficient smart materials. The Wnt/\(\beta\)-catenin pathway is crucial for bone tissue regeneration, as it plays a significant role in osteoblast differentiation and bone formation. [PERSON] et al. [63] showed that strontium incorporation enhances osteoblast differentiation and activity through the activation of the Wnt/\(\beta\)-catenin signaling pathway. This pathway's activation promotes the expression of osteogenic markers and reduces the levels of pro-inflammatory cytokines such as TNF-\(\alpha\) and IL-1\(\beta\), creating a more favorable environment for bone regeneration. Similarly, [PERSON] et al. [20] demonstrated that strontium-doped mesoporous bioactive glass scaffolds significantly promoted osteogenic differentiation and angiogenesis by activating the Wnt/\(\beta\)-catenin pathway. [PERSON] et al. [25] also found that strontium-substituted hydroxyapatite coatings on magnesium alloys enhanced osteogenic differentiation through Wnt/\(\beta\)-catenin activation, further highlighting its importance in bone regeneration. [PERSON] et al. [74] emphasized the role of the Wnt/\(\beta\)-catenin pathway in sequential signaling for bone formation, highlighting the need for more studies exploring this pathway in the context of strontium-doped biomaterials. The BMP-2 pathway is another critical regulator of bone formation, involved in the differentiation of mesenchymal stem cells into osteoblasts. [PERSON] et al. [20] and [PERSON] et al. [25] both reported that BMP-2 signaling is significantly enhanced by strontium-doped biomaterials, promoting osteogenic differentiation and mineralization. [PERSON] et al. [37] confirmed these findings by showing that strontium-substituted hydroxyapatite coatings upregulated BMP-2 expression, along with other osteogenic and angiogenic markers, in rat bone marrow mesenchymal stem cells (rBMCs). [PERSON] et al. [31] further demonstrated that strontium-doped hydroxyapatite biocreams with micro-nano-hybrid surfaces significantly promoted the proliferation, differentiation, and angiogenic activity of bone marrow stromal cells (BMSCs) through the activation of BMP-2 and VEGF, directly related to the observed effects on bone tissue regeneration. BMP-2 initiates the process by signaling through the SMAD pathway, leading to the activation of Runx2, a key transcription factor in osteoblast differentiation. [PERSON] et al. [14] supported the role of BMP-2 in osteogenesis by demonstrating increased levels of this marker in the presence of strontium-doped materials. Runx2 is a master transcription factor for osteoblast differentiation, and its activation is vital for bone tissue development. [PERSON] et al. [50] demonstrated that air-plasma-treated titanium alloy coatings with strontium-doped phosphate significantly enhance osteogenic activity by upregulating Runx2. [PERSON] et al. [75] also found that SrCHA increased the expression of Runx2, Osterix, ALP, and collagen 1a1 genes, leading to higher osteogenic activity and bone formation. These findings underscore the importance of Runx2 in mediating the osteogenic effects of strontium-doped biomaterials. [PERSON] et al. [76] highlighted the critical role of Runx2 in initiating the mineralization process, which is supported by studies showing increased Runx2 expression in the presence of strontium-containing biomaterials [33; 40; 55].