Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, PR China.
Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510080, PR China.
ACS Biomater Sci Eng. 2024 Jul 8;10(7):4323-4335. doi: 10.1021/acsbiomaterials.4c00549. Epub 2024 Jun 11.
In patients with diabetes, endoplasmic reticulum stress (ERS) is a crucial disrupting factor of macrophage homeostasis surrounding implants, which remains an obstacle to oral implantation success. Notably, the ERS might be modulated by the implant surface morphology. Titania nanotubes (TNTs) may enhance diabetic osseointegration. However, a consensus has not been achieved regarding the tube-size-dependent effect and the underlying mechanism of TNTs on diabetic macrophage ERS. We manufactured TNTs with small (30 nm) and large diameters (100 nm). Next, we assessed how the different titanium surfaces affected diabetic macrophages and regulated ERS and Ca homeostasis. TNTs alleviated the inflammatory response, oxidative stress, and ERS in diabetic macrophages. Furthermore, TNT30 was superior to TNT100. Inhibiting ERS abolished the positive effect of TNT30. Mechanistically, topography-induced extracellular Ca influx might mitigate excessive ERS in macrophages by alleviating ER Ca depletion and IP3R activation. Furthermore, TNT30 attenuated the peri-implant inflammatory response and promoted osseointegration in diabetic rats. TNTs with small nanodiameters attenuated ERS and re-established diabetic macrophage hemostasis by inhibiting IP3R-induced ER Ca depletion.
在糖尿病患者中，内质网应激（ERS）是围绕植入物的巨噬细胞动态平衡的关键破坏因素，这仍然是口腔植入成功的障碍。值得注意的是，植入物表面形态可以调节 ERS。二氧化钛纳米管（TNTs）可能增强糖尿病患者的骨整合。然而，关于 TNTs 对糖尿病巨噬细胞 ERS 的管径依赖性影响及其潜在机制尚未达成共识。我们制造了具有小（30nm）和大直径（100nm）的 TNTs。接下来，我们评估了不同钛表面如何影响糖尿病巨噬细胞并调节 ERS 和钙动态平衡。TNTs 减轻了糖尿病巨噬细胞的炎症反应、氧化应激和 ERS。此外，TNT30 优于 TNT100。抑制 ERS 消除了 TNT30 的积极作用。在机制上，拓扑诱导的细胞外 Ca 内流可能通过减轻 ER Ca 耗竭和 IP3R 激活来减轻巨噬细胞中过度的 ERS。此外，TNT30 减轻了糖尿病大鼠种植体周围的炎症反应并促进了骨整合。小纳米直径的 TNTs 通过抑制 IP3R 诱导的 ER Ca 耗竭来减轻 ERS 并重新建立糖尿病巨噬细胞止血。
