Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.
Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China.
Int J Mol Sci. 2023 Jul 13;24(14):11431. doi: 10.3390/ijms241411431.
Peri-implantitis requires clinical treatments comprised of mechanical and chemical debridement to remove bacterial biofilms. Bone regeneration on the titanium surface after debridement has been a topical issue of peri-implantitis treatments. Increasing evidence has revealed that the immune microenvironment plays a key role in regulating the bone regeneration process. However, it remains unclear what kind of immune microenvironment the titanium surface induces after debridement. In the study, model titanium surface after debridement was prepared via biofilm induction and mechanical and chemical debridement in vitro. Then, the macrophages and naïve CD4 T lymphocytes were cultured on the titanium surface after debridement for immune microenvironment evaluation, with the original titanium surface as the control. Next, to regulate the immune microenvironment, 2-DG, a glycolysis inhibitor, was further incorporated to regulate macrophages and CD4 T lymphocytes at the same time. Surface characterization results showed that the bacterial biofilms were completely removed, while the micro-morphology of titanium surface altered after debridement, and the element composition did not change. Compared with the original titanium disc, titanium surface after debridement can lead to the inflammatory differentiation of macrophages and CD4 T lymphocytes. The percentage of M1 and Th17 inflammatory cells and the expression of their inflammatory factor genes are upregulated. However, 0.3 mmol of 2-DG can significantly reduce the inflammatory differentiation of both macrophages and CD4 T lymphocytes and inhibit their expression of inflammatory genes. In conclusion, although bacterial biofilms were removed from titanium surface after debridement, the surface topography changes could still induce immune imbalance and form an inflammatory immune microenvironment. However, this inflammatory immune microenvironment can be effectively reversed by 2-DG in vitro, thus creating an immune microenvironment conducive to osteogenesis, which might provide a new perspective for future therapy of peri-implantitis.
种植体周围炎需要临床治疗，包括机械和化学清创以去除细菌生物膜。清创后钛表面的骨再生一直是种植体周围炎治疗的一个热门问题。越来越多的证据表明，免疫微环境在调节骨再生过程中起着关键作用。然而，目前尚不清楚清创后钛表面会诱导什么样的免疫微环境。在这项研究中，通过体外生物膜诱导和机械化学清创制备了清创后的模型钛表面。然后，将巨噬细胞和幼稚 CD4 T 淋巴细胞培养在清创后的钛表面上进行免疫微环境评估，以原始钛表面作为对照。接下来，为了调节免疫微环境，进一步加入了糖酵解抑制剂 2-DG 以同时调节巨噬细胞和 CD4 T 淋巴细胞。表面特征结果表明，细菌生物膜被完全去除，而清创后钛表面的微观形貌发生改变，元素组成没有变化。与原始钛盘相比，清创后的钛表面可导致巨噬细胞和 CD4 T 淋巴细胞的炎症分化。M1 和 Th17 炎症细胞的比例及其炎症因子基因的表达上调。然而，0.3mmol 的 2-DG 可显著降低巨噬细胞和 CD4 T 淋巴细胞的炎症分化，并抑制其炎症基因的表达。总之，尽管清创后钛表面的细菌生物膜被去除，但表面形貌的变化仍可诱导免疫失衡并形成炎症性免疫微环境。然而，这种炎症性免疫微环境可以在体外被 2-DG 有效逆转，从而创造出有利于成骨的免疫微环境，这可能为种植体周围炎的未来治疗提供新的视角。
