## 4 Discussion  
### Functionalization with Strontium  
When a biodegradable biomaterial is functionalized with a particular ion such as strontium, it is expected that its release in the intercellular medium induces some biological response, activating or deactivating specific cellular pathways. It is known that as in any therapeutic process, the levels of strontium ion release should be within a specific range so that its effect on the tissue is beneficial without presenting toxicity to the organism ([PERSON] et al., 2019). The diversity in the shapes and types of strontium-doped calcium phosphate biomaterials, as summarized in Table 3, plays a significant role in their efficacy for bone therapy and material testing. Discs and rods, for instance, provide a standardized geometry that is ideal for in vitro testing of cellular responses, such as proliferation, differentiation, and cytotoxicity. Studies using discs, like those by [PERSON] et al. (2018) and [PERSON] et al. (2019), demonstrated enhanced osteoblast differentiation and biocompatibility, which are critical for preliminary material evaluation. \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Article** & **Cell Type** & **Test Performed** & **Effects** \\ \hline [PERSON] et al. (2019) & Rabbit bone marrow stromal cells (rBMCs) & Cell adhesion assay, cell proliferation assay, ALP activity assay, Alizarin red staining & Enhanced cell adhesion, increased proliferation, higher ALP activity, and greater mineralization in Sr-CaP-p group \\ \hline [PERSON] et al. (2019) & Osteoblast (MC3T3-E1)/primary rabbit osteoclasts & Alamar Blue, ALP and resorption pits & Decreased resorption pits and ALP expression, similar to the control \\ \hline [PERSON] et al. (2019) & Mouse Raw 264.7 macrophages, MC3T3-E1 osteoblasts & MTT assay, gene expression (IL1-1ß, IL-6, TNF-\(\alpha\), cytokine secretion (ELISA for IL-1ß, IL-6, TNF-\(\alpha\), RTNFA, RTNFA, MCP-1, MLP-1a), real-time PCR (OPG, ALP, OCN, COL-I, c-fos) & Decreased macrophage proliferation, down-regulated gene expression and cytokine secretion of IL-1ß, IL-6, TNF-\(\alpha\), increased osteoblast viability, and osteogenic gene expression \\ \hline [PERSON] et al. (2019) & Osteoblast-like (MG63) & MTT and ALP & The 10\% Sr-H\(\dot{\alpha}\) promoted proliferation while higher concentrations decreased it \\ \hline [PERSON] et al. (2019) & Fibroblasts (L929) & MTT & Similar to the control \\ \hline [PERSON] et al. (2019) & Pre-osteoblastic MC3T3-E1 cells & ALP staining, real-time PCR & Increased osteoblast differentiation \\ \hline [PERSON] et al. (2019) & Rat MSCs & CCK-8, ALP, OCN, OPN and Type 1 collagen & Interrod spacing larger than 137 nm inhibited in vitro mesenchymal stem cell functions \\ \hline \hline \end{tabular} OSC = osteocalcin; SEM = scanning electron microscopy; OPG = osteeoprotein; TLS = tube-like structure; CIS = confocal laser scanning.  
\end{table} 
Table 4: _Cont._Scaffolds, on the other hand, mimic the three-dimensional structure of bone more closely and are thus more relevant for in vivo applications. For example, the porous scaffolds used by [PERSON] et al. [21] and [PERSON] et al. [24] showed significant improvements in new bone formation and angiogenesis, highlighting their potential for effective bone regeneration therapies. The use of scaffolds allows for better integration with the host tissue, facilitating cell infiltration and vascularization, which are essential for successful bone healing. Additionally, scaffolds can be fabricated using advanced techniques like 3D printing, employing nanomaterials to create complex anatomical features for bone therapy [67]. Powdered materials, as utilized by [PERSON] et al. [15] and [PERSON] et al. [12], offer versatility in being mixed with various carriers or used as coatings. This flexibility can be advantageous in both research and clinical settings, allowing for customized application methods tailored to specific needs.