Regulation of angiogenesis during osseointegration by titanium surface microstructure and energy.

Regulation of angiogenesis during osseointegration by titanium surface microstructure and energy.
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DOI:
10.1016/j.biomaterials.2010.02.071
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发表时间:
2010-06
期刊:
影响因子:
14
通讯作者:
Boyan BD
Boyan BD
中科院分区:
工程技术1区
文献类型:
--
作者:
Raines AL;Olivares-Navarrete R;Wieland M;Cochran DL;Schwartz Z;Boyan BD

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粗糙的钛表面微结构和高表面能促进成骨细胞分化,这种反应是通过α-2-β-1整合素信号传导实现的。然而,植入材料的临床成功不仅取决于骨整合,还取决于种植体周围骨中新生血管的形成。在这里,我们验证了钛表面微地形和能量通过α-2-β-1信号相互作用来调节血管生成生长因子表达的假设。将原代人成骨细胞(HOB)、MG6 3细胞和α2整合素沉默的MG6 3细胞分别培养在不同表面形貌和能量的钛圆盘上。检测血管内皮生长因子-A(VEGF-A)、碱性成纤维细胞生长因子(FGF-2)、表皮生长因子(EGF)和血管生成素-1(Ang-1)的分泌水平。在SLA和modSLA底物上,MG63和HOB细胞的VEGF-A分别增加170%和250%,178%和435%。在MG63培养中,SLA和modSLA表面的成纤维细胞生长因子-2水平分别增加20和40倍,而表皮生长因子水平分别增加4和6倍。这些因素在HOB培养中是检测不到的。血管紧张素-1水平在所有表面均无变化。ModSLA MG63培养基能更快地诱导内皮细胞分化,这一作用可被抗血管内皮生长因子-A抗体抑制。1-α,25(OH)2D3作用于MG63细胞后,其表面和外周血中的血管内皮生长因子-A水平均升高。沉默成纤维细胞生长因子2整合素亚单位可增加α-A水平,降低FGF2水平。这些结果表明,钛表面微形貌和能量调节成骨细胞分泌血管生长因子,这种调节至少部分是通过α-2-β-1整合素信号来实现的。
Rough titanium (Ti) surface microarchitecture and high surface energy have been shown to increase osteoblast differentiation, and this response occurs through signaling via the α2β1 integrin. However, clinical success of implanted materials is dependent not only upon osseointegration but also on neovascularization in the peri-implant bone. Here we tested the hypothesis that Ti surface microtopography and energy interact via α2β1 signaling to regulate the expression of angiogenic growth factors. Primary human osteoblasts (HOB), MG63 cells and MG63 cells silenced for α2 integrin were cultured on Ti disks with different surface microtopographies and energies. Secreted levels of vascular endothelial growth factor-A (VEGF-A), basic fibroblast growth factor (FGF-2), epidermal growth factor (EGF), and angiopoietin-1 (Ang-1) were measured. VEGF-A increased 170% and 250% in MG63 cultures, and 178% and 435% in HOB cultures on SLA and modSLA substrates, respectively. In MG63 cultures, FGF-2 levels increased 20 and 40-fold while EGF increased 4 and 6-fold on SLA and modSLA surfaces. These factors were undetectable in HOB cultures. Ang-1 levels were unchanged on all surfaces. Media from modSLA MG63 cultures induced more rapid differentiation of endothelial cells and this effect was inhibited by anti-VEGF-A antibodies. Treatment of MG63 cells with 1α,25(OH)2D3 enhanced levels of VEGF-A on SLA and modSLA. Silencing the α2 integrin subunit increased VEGF-A levels and decreased FGF-2 levels. These results show that Ti surface microtopography and energy modulate secretion of angiogenic growth factors by osteoblasts and that this regulation is mediated at least partially via α2β1 integrin signaling.
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