Vallés Gema, Gil-Garay Enrique, Munuera Luis, Vilaboa Nuria
Unidad de Investigación, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain.
Biomaterials. 2008 May;29(15):2326-35. doi: 10.1016/j.biomaterials.2008.02.011. Epub 2008 Mar 3.
Titanium (Ti) and its alloys have widespread uses as implant materials for orthopaedic and dental applications. To improve their surface characteristics, modifications that give rise to an outer ceramic layer of rutile have been developed. It is expected that after a long period of service, rutile particles will arise from these modified surfaces. Rutile particles have recently been proposed as reinforcement agents of substrates designed for bone tissue engineering applications. In this study, the ability of Ti and rutile particles to modulate secretion of soluble factors involved in bone turnover has been assayed in an in vitro co-culture system of macrophages and human osteoblasts that allows the exchange of soluble factors between both cell types without direct cell contact. Exposure of co-cultured macrophages to sub-cytotoxic doses of Ti or rutile particles did not modify the osteoblastic expression of surface RANKL or the secretion of OPG into the media. Both IL-6 and PGE2 levels increased to a similar extent after treatment with rutile or Ti particles. M-CSF and GM-CSF levels were lower after treatment with rutile particles than with Ti. Experiments employing neutralising antibodies indicate that exposure of co-cultured macrophages to both Ti-based particles induces the release of M-CSF, GM-CSF, IL-6 and PGE2 through up-regulation of IL-1beta and TNF-alpha. We comparatively examined the response of co-cultured macrophages, osteoblasts or both types of cells after exposure to particles. The results indicate that interactions of osteoblasts with particles can modulate the extent of the response initiated by macrophages. Maximal levels of secretions of all tested factors were reached after exposure of co-cultured cells to Ti particles, which is suggestive of the lower bioreactivity of rutile particles.
钛（Ti）及其合金作为骨科和牙科植入材料有着广泛应用。为改善其表面特性，已开发出能形成金红石外层陶瓷层的改性方法。预计在长期使用后，这些改性表面会产生金红石颗粒。最近，金红石颗粒被提议作为用于骨组织工程应用的基质增强剂。在本研究中，在巨噬细胞和人成骨细胞的体外共培养系统中检测了Ti和金红石颗粒调节参与骨转换的可溶性因子分泌的能力，该系统允许两种细胞类型之间交换可溶性因子而无需直接细胞接触。将共培养的巨噬细胞暴露于亚细胞毒性剂量的Ti或金红石颗粒，并未改变表面RANKL的成骨细胞表达或向培养基中分泌OPG。用金红石或Ti颗粒处理后，IL-6和PGE2水平均有相似程度的升高。用金红石颗粒处理后，M-CSF和GM-CSF水平低于用Ti处理后的水平。使用中和抗体的实验表明，将共培养的巨噬细胞暴露于两种基于Ti的颗粒会通过上调IL-1β和TNF-α诱导M-CSF、GM-CSF、IL-6和PGE2的释放。我们比较了共培养的巨噬细胞、成骨细胞或两种细胞类型在暴露于颗粒后的反应。结果表明，成骨细胞与颗粒的相互作用可调节巨噬细胞引发的反应程度。共培养细胞暴露于Ti颗粒后，所有测试因子的分泌水平达到最高，这表明金红石颗粒的生物反应性较低。
