Shen Ke, Tang Qiang, Fang Xingtang, Zhang Chunlei, Zhu Zhaojing, Hou Yanhua, Lai Min
School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116, China.
Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing Medical and Pharmaceutical College, Chongqing 401331, China.
Mater Sci Eng C Mater Biol Appl. 2020 Nov;116:111241. doi: 10.1016/j.msec.2020.111241. Epub 2020 Jun 28.
Controlling macrophage response to biomaterials is critical for the reduction of inflammation after implantation. Here we designed a sustained release system from TiO 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。在此，我们设计了一种由二氧化钛纳米管（TNTs）构成的缓释系统，以改善具有抗炎特性的钛植入物的成骨作用。首先通过阳极氧化在钛表面制备直径约70纳米的TNTs，直接填充抗炎药物地塞米松（DEX），然后用壳聚糖（CHI）多层膜覆盖。在体外将原代成骨细胞和巨噬细胞（RAW 264.7）培养在未处理和处理过的钛表面。在涂有CHI的充满Dex的TNTs表面生长的成骨细胞显示出更高的碱性磷酸酶（ALP）活性和矿化能力，这与对包括I型胶原（Col I）、骨钙素（OCN）、骨桥蛋白（OPN）和 runt相关转录因子2（Runx2）在内的成骨细胞基因的qRT-PCR分析结果一致。相比之下，在充满Dex的TNTs、涂有CHI的TNTs和涂有CHI的充满Dex的TNTs上，巨噬细胞产生的一氧化氮（NO）和促炎细胞因子（TNF-α和IL-1β）的蛋白水平显著降低，特别是与钛和TNTs表面相比，在涂有CHI的充满Dex的TNTs表面更低。这些结果表明，涂有CHI的充满Dex的TNTs增强了成骨细胞分化并降低了巨噬细胞的炎症反应。本文提出的方法为开发基于钛的植入物对TNTs进行改性提供了新的见解。
