Additive manufacturing (AM) techniques have provided many opportunities for the rational design of porous metallic biomaterials with complex and precisely controlled topologies that give rise to unprecedented combinations of mechanical, physical, and biological properties. These favorable properties can be enhanced by surface biofunctionalization to enable full tissue regeneration and minimize the risk of implant-associated infections (IAIs). There is, however, an increasing need to investigate the immune responses triggered by surface biofunctionalized AM porous metals. Here, we studied the immunomodulatory effects of AM porous titanium (Ti-6Al-4V) printed using selective laser melting, and of two additional groups consisting of AM implants surface biofunctionalized using plasma electrolytic oxidation (PEO) with/without silver nanoparticles. The responses of human primary macrophages and human mesenchymal stromal cells (hMSCs) were studied in terms of cell viability, cell morphology and biomarkers of macrophage polarization. Non-treated AM porous titanium triggered a strong pro-inflammatory response in macrophages, albeit combined with signs of anti-inflammatory effects. The PEO treatment of AM porous titanium implants showed a higher potential to induce polarization towards a pro-repair macrophage phenotype. We detected no cytotoxicity against hMSCs in any of the groups. However, the incorporation of silver nanoparticles resulted in strong cytotoxicity against attached macrophages. The results of this study indicate the potential immunomodulatory effects of the AM porous titanium enhanced with PEO treatment, and point towards caution and further research when using silver nanoparticles for preventing IAIs.

中文翻译：

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表面生物功能化 3D 打印多孔钛植入物的免疫调节。

增材制造 (AM) 技术为合理设计具有复杂且精确控制的拓扑结构的多孔金属生物材料提供了许多机会，从而产生了前所未有的机械、物理和生物特性组合。这些有利的特性可以通过表面生物功能化来增强，以实现全组织再生并将植入物相关感染 (IAI) 的风险降至最低。然而，越来越需要研究由表面生物功能化 AM 多孔金属引发的免疫反应。在这里，我们研究了使用选择性激光熔化打印的 AM 多孔钛 (Ti-6Al-4V) 的免疫调节作用，以及使用等离子体电解氧化 (PEO) 使用/不使用银纳米粒子对表面生物功能化的 AM 植入物组成的两个附加组的免疫调节作用。在细胞活力、细胞形态和巨噬细胞极化的生物标志物方面研究了人类原代巨噬细胞和人类间充质基质细胞 (hMSCs) 的反应。未经处理的 AM 多孔钛在巨噬细胞中引发了强烈的促炎反应，尽管结合了抗炎作用的迹象。AM 多孔钛植入物的 PEO 处理显示出更高的潜力，以诱导朝向促修复巨噬细胞表型的极化。我们在任何组中均未检测到对 hMSC 的细胞毒性。然而，银纳米颗粒的掺入导致对附着的巨噬细胞的强烈细胞毒性。本研究结果表明，经 PEO 处理增强的 AM 多孔钛具有潜在的免疫调节作用，