Abstract

Inflammatory response is an essential part of optimal tissue-implant integration and the regeneration process. Due to their highly plastic properties, macrophages display phenotypic changes during inflammatory signaling. Investigating these changes on implant surfaces is essential for evaluating implant stability and longevity. In order to control macrophage polarization, IL-4 was conjugated to titanium dioxide nanotubes (TNTs) through polydopamine, and successful fabrication was checked by scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and contact angle, respectively. In vitro experiments including immunofluorescence staining, cell proliferation, the expression of genes associated with pro-inflammatory M1 phenotype (tumor necrosis factor-alpha (TNF-α), Interleukin-18 (IL-18)) and cytokines related to the anti-inflammatory M2 phenotype (IL-4 and IL-10), and the production of nitric oxide (NO) and cytokines TNF-α, IL-10 were detected. Macrophage response showed that IL-4 functionalized TNTs favored macrophage polarization towards an anti-inflammatory M2-phenotype. This study provides a new strategy for use in medical devices and the development of advanced nano-biomaterials in immunotherapy applications.

摘要

炎症反应是最佳组织植入物整合和再生过程的重要组成部分。由于其高度可塑性，巨噬细胞在炎症信号传导过程中表现出表型变化。研究种植体表面的这些变化对于评估种植体稳定性和寿命至关重要。为了控制巨噬细胞极化，IL-4 通过聚多巴胺与二氧化钛纳米管 (TNTs) 结合，并通过扫描电子显微镜 (SEM)、原子力显微镜 (AFM)、X 射线光电子能谱 (XPS) 检查制造成功和接触角，分别。体外实验包括免疫荧光染色、细胞增殖、与促炎 M1 表型相关的基因表达（肿瘤坏死因子-α (TNF-α)、白细胞介素-18 (IL-18)）和与抗炎 M2 表型相关的细胞因子(IL-4 和 IL-10)，并检测到一氧化氮 (NO) 和细胞因子 TNF-α、IL-10 的产生。巨噬细胞反应表明，IL-4 功能化的 TNT 有利于巨噬细胞向抗炎 M2 表型极化。这项研究为医疗器械的使用和免疫治疗应用中先进纳米生物材料的开发提供了一种新策略。