Secchi A G, Grigoriou V, Shapiro I M, Cavalcanti-Adam E A, Composto R J, Ducheyne P, Adams C S
Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
J Biomed Mater Res A. 2007 Dec 1;83(3):577-84. doi: 10.1002/jbm.a.31007.
A major cause of implant failure in skeletal tissues is failure of osseointegration, often due to lack of adhesion of cells to the titanium (Ti) alloy interface. Since arginine-glycine-aspartic acid (RGD)-containing peptides have been shown to regulate osteoblast adhesion, we tested the hypothesis that, bound to a Ti surface, these peptides would promote osteoblasts differentiation, while at the same time inhibit apoptosis. RGDS and RGES (control) peptides were covalently linked to Ti discs using an APTS linker. While the grafting of both RGDS and RGES significantly increased Ti surface roughness, contact angle analysis showed that APTS significantly increased the surface hydrophobicity; when the peptides were tethered to Ti, this was reduced. To evaluate attachment, MC3T3-E1 osteoblast cells were grown on these discs. Significantly more cells attached to the Ti-grafted RGDS then the Ti-grafted RGES control. Furthermore, expression of the osteoblasts phenotype was significantly enhanced on the Ti-grafted RGDS surface. When cells attached to the Ti-grafted RGDS were challenged with staurosporine, an apoptogen, there was significant inhibition of apoptosis; in contrast, osteoblasts adherent to the Ti-grafted RGES were killed. It is concluded that RGD-containing peptides covalently bonded to Ti promotes osteoblasts attachment and survival with minimal changes to the surface of the alloy. Therefore, such modifications to Ti would have the potential to promote osseointegration in vivo.
骨骼组织中植入物失败的一个主要原因是骨整合失败，这通常是由于细胞与钛（Ti）合金界面缺乏黏附所致。由于含精氨酸-甘氨酸-天冬氨酸（RGD）的肽已被证明可调节成骨细胞黏附，我们测试了这样一个假设，即这些肽结合到Ti表面时，会促进成骨细胞分化，同时抑制细胞凋亡。使用APTS连接子将RGDS和RGES（对照）肽共价连接到Ti盘上。虽然RGDS和RGES的接枝均显著增加了Ti表面粗糙度，但接触角分析表明，APTS显著增加了表面疏水性；当肽连接到Ti上时，表面疏水性降低。为了评估细胞黏附情况，将MC3T3-E1成骨细胞培养在这些盘上。与Ti接枝的RGES对照相比，附着在Ti接枝的RGDS上的细胞明显更多。此外，在Ti接枝的RGDS表面，成骨细胞表型的表达显著增强。当附着在Ti接枝的RGDS上的细胞用促凋亡剂星形孢菌素处理时，细胞凋亡受到显著抑制；相比之下，附着在Ti接枝的RGES上的成骨细胞则被杀死。得出的结论是，与Ti共价结合的含RGD肽可促进成骨细胞附着和存活，同时对合金表面的改变最小。因此，对Ti进行这样的修饰有可能促进体内骨整合。
