Controlling macrophage response to biomaterials is critical for the reduction of inflammation after implantation. Here we designed a sustained release system from TiO₂ nanotubes (TNTs) to improve osteogenesis on titanium implants with anti-inflammatory properties. TNTs (around 70 nm diameter) were first fabricated on titanium surfaces by anodization, directly filled with the anti-inflammatory drug, dexamethasone (DEX) and then covered by chitosan (CHI) multilayer films. Primary osteoblast and macrophage (RAW 264.7) cells were cultured on untreated and treated titanium surfaces in vitro. Osteoblasts grown on CHI-coated Dex-filled TNTs surfaces displayed higher alkaline phosphatase (ALP) and mineralization, which was consistent with qRT-PCR analysis of osteoblastic genes including collagen type I (Col I), osteocalcin (OCN), osteopontin (OPN) and runt related transcription factor 2 (Runx2). In contrast, protein levels of nitric oxide (NO) and proinflammatory cytokines (TNF-α and IL-1β) from macrophages on Dex-filled TNTs, CHI-coated TNTs and CHI-coated Dex-filled TNTs were significantly lower, especially on CHI-coated Dex-filled TNTs surfaces compared to levels on titanium and TNTs. These results indicate that CHI-coated Dex-filled TNTs enhanced osteoblast differentiation and decreased the inflammatory response of macrophages. The approach presented here provides new insight into the modification of TNTs for the development of titanium-based implants.

控制巨噬细胞对生物材料的反应对于减少植入后的炎症至关重要。在这里，我们设计了一种由TiO ₂纳米管（TNT）制成的缓释系统，以改善具有抗炎特性的钛植入物的成骨作用。TNT（直径约70 nm）首先通过阳极氧化在钛表面上制造，直接填充有抗炎药地塞米松（DEX），然后被壳聚糖（CHI）多层膜覆盖。原代成骨和巨噬细胞（RAW 264.7）细胞在未处理的培养和处理过的钛表面体外。在涂有CHI的Dex填充TNT表面上生长的成骨细胞显示出更高的碱性磷酸酶（ALP）和矿化作用，这与成骨细胞基因（包括I型胶原（Col I），骨钙蛋白（OCN），骨桥蛋白（OPN））的qRT-PCR分析一致与矮子相关的转录因子2（Runx2）。相反，Dext填充的TNT，CHI包被的TNT和CHI包被的Dex填充的TNT上巨噬细胞的一氧化氮（NO）和促炎细胞因子（TNF-α和IL-1β）的蛋白质水平显着降低，尤其是在CHI上与钛和TNT上的水平相比，Dex填充的TNT涂层表面。这些结果表明，CHI包被的Dex填充TNT增强了成骨细胞分化并降低了巨噬细胞的炎症反应。