Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, People's Republic of China.
Department of Oral Implant, School of Stomatology, Hospital of Stomatology, Tongji University, Shanghai, People's Republic of China.
Int J Nanomedicine. 2020 Jun 30;15:4659-4676. doi: 10.2147/IJN.S245608. eCollection 2020.
Titanium implants are widely used in dental and orthopedic medicine. Nevertheless, there is limited osteoinductive capability of titanium leading to a poor or delayed osseointegration, which might cause the failure of the implant therapy. Therefore, appropriate modification on the titanium surface for promoting osseointegration of existing implants is still pursued.
Graphene oxide (GO) is a promising candidate to perform implant surface biofunctionalization for modulating the interactions between implant surface and cells. So the objective of this study was to fabricate a bioactive GO-modified titanium implant surface with excellent osteoinductive potential and further investigate the underlying biological mechanisms.
The large particle sandblasting and acid etching (SLA, commonly used in clinical practice) surface as a control group was first developed and then the nano-GO was deposited on the SLA surface via an ultrasonic atomization spraying technique to create the SLA/GO group. Their effects on rat bone marrow mesenchymal stem cells (BMSCs) responsive behaviors were assessed in vitro, and the underlying biological mechanisms were further systematically investigated. Moreover, the osteogenesis performance in vivo was also evaluated.
The results showed that GO coating was fabricated on the titanium substrates successfully, which endowed SLA surface with the improved hydrophilicity and protein adsorption capacity. Compared with the SLA surface, the GO-modified surface favored cell adhesion and spreading, and significantly improved cell proliferation and osteogenic differentiation of BMSCs in vitro. Furthermore, the FAK/P38 signaling pathways were proven to be involved in the enhanced osteogenic differentiation of BMSCs, accompanied by the upregulated expression of focal adhesion (vinculin) on the GO coated surface. The enhanced bone regeneration ability of GO-modified implants when inserted into rat femurs was also observed and confirmed that the GO coating induced accelerated osseointegration and osteogenesis in vivo.
GO modification on titanium implant surface has potential applications for achieving rapid bone-implant integration through the mediation of FAK/P38 signaling pathways.
钛植入物在牙科和骨科医学中被广泛应用。然而，钛的成骨能力有限，导致骨整合不良或延迟，这可能导致植入物治疗的失败。因此，仍然需要对现有的钛植入物表面进行适当的改性，以促进其骨整合。
氧化石墨烯（GO）是一种很有前途的候选材料，可以对植入物表面进行生物功能化修饰，以调节植入物表面与细胞之间的相互作用。因此，本研究的目的是制备具有优异成骨诱导潜力的生物活性 GO 修饰钛植入物表面，并进一步研究其潜在的生物学机制。
首先制备了大颗粒喷砂酸蚀（SLA，临床上常用）表面作为对照组，然后通过超声雾化喷涂技术将纳米 GO 沉积在 SLA 表面上，以制备 SLA/GO 组。在体外评估它们对大鼠骨髓间充质干细胞（BMSCs）反应行为的影响，并进一步系统研究其潜在的生物学机制。此外，还评估了其体内成骨性能。
结果表明，GO 涂层成功地制备在钛基底上，使 SLA 表面具有改善的亲水性和蛋白质吸附能力。与 SLA 表面相比，GO 修饰表面有利于细胞黏附和铺展，并显著促进 BMSCs 的体外增殖和成骨分化。此外，研究证明 FAK/P38 信号通路参与了 BMSCs 成骨分化的增强，伴随着 GO 涂层表面上粘着斑（ vinculin ）的上调表达。将 GO 改性植入物插入大鼠股骨中也观察到增强的骨再生能力，并证实 GO 涂层在体内诱导了加速的骨整合和成骨作用。
GO 对钛植入物表面的修饰通过 FAK/P38 信号通路的介导，具有实现快速骨-植入物整合的潜力。
