微米級之兩相磷酸鈣材料在臨床上已被證實在骨組織修復中具有效果，但目前對於奈米等級之兩相磷酸鈣材料之研究則仍非常少，尤其是兩相奈米材料對於成骨細胞分化、免疫調控與發炎狀態下之微環境的影響。本研究運用奈米研磨分散技術，通過使用聚合羧酸作為分散劑成功製備出非針狀之奈米顆粒，此材料具備無細胞毒性、表面帶負電與能夠進入細胞之特性。我們的結果顯示，使用較低濃度的兩相奈米顆粒處理人類成骨細胞，可顯著增加鹼性磷酸酶（ALP）活性，並增強與成骨相關的基因表達，其中包括ALP、RUNX2與OPN。此外，兩相奈米顆粒還表現出免疫調節效果，在無發炎誘導的條件下，以兩相奈米顆粒處理單核球細胞來源之巨噬細胞，可以降低發炎性細胞因子的基因表現量，其中包括IL-1beta、TNF-alpha和IL-6。在LPS誘導發炎的情況下，兩相奈米顆粒可以有效的抑制LPS所誘發之發炎性細胞因子的基因與蛋白質表現量。本研究進一步以條件培養液的實驗發現，兩相奈米顆粒能夠降低由LPS刺激的巨噬細胞培養液對成骨細胞分化和礦化的負面影響。這些發現說明了兩相奈米顆粒在骨組織修復和再生的臨床應用中具有潛力。總體而言，本研究開發出之兩相奈米顆粒能促進成骨細胞骨化並俱備免疫調節特性，為解決臨床手術中的發炎性骨溶解併發症提供了潛在的治療途徑。

Micron-scale biphasic calcium phosphate materials have been effective in bone tissue repair, but there is limited research on their nanoscale counterparts. This study focuses on synthesizing granular-shaped biphasic calcium phosphate nanomaterials with beneficial properties such as negatively charged surfaces, non-cytotoxicity, and cellular penetration. These characteristics were achieved using a nanogrinding dispersion method with polymeric carboxylic acid as the dispersant. Our results demonstrate that treating human osteoblasts with lower concentration of these nanoparticles significantly increases alkaline phosphatase (ALP) activity and enhances the expression of genes related to osteogenesis. Furthermore, the biphasic calcium phosphate nanoparticles exhibit immunomodulatory effects. When applied to THP-1-derived macrophages, these nanomaterials reduce the expression of several inflammatory genes. They also inhibit the heightened inflammatory gene expression and inflammatory protein production induced by lipopolysaccharide (LPS) in THP-1-derived macrophages. Importantly, biphasic calcium phosphate nanoparticles can reverse the negative effects of LPS-stimulated macrophage-conditioned medium on osteoblast osteogenesis and mineralization. These findings suggest that biphasic calcium phosphate nanoparticles have the potential utility for clinical applications in bone tissue repair and regeneration. In summary, this study highlights the advantageous properties of biphasic calcium phosphate nanoparticles in promoting osteogenesis and modulating immune responses, offering a potential pathway for addressing inflammatory osteolysis in clinical surgery.

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