现如今，口腔牙列缺损的患者通常会将种植修复作为第一选择。种植修复可以极大的提高患者的生活质量，但是它也存在着一些不可避免的问题。普遍的观点认为，在进行种植修复后，患者需要至少3个月才能获得良好的种植体骨结合的效果。当患者患有骨质疏松症、牙周炎等疾病时，愈合过程则需要花费更长的时间。为了减少此类疾病对种植体骨结合产生的影响，提高患者的种植体成功率，加快患者临床治疗的过程，缩短愈合时间，学者致力于构建新型种植体表面来促进种植体骨结合的形成。近年来，锂元素因其在成骨活动中的突出表现而备受学者们的关注。锂元素是治疗躁狂症等精神类疾病的主要药物之一，有学者发现，服用含锂药物可以提高患者体内的骨密度。因此，本研究通过水热法在大颗粒喷砂酸蚀(sandblasted，large-grit，acid-etched，SLA)的种植体表面基础上制备了一种新型掺锂表面，通过对该表面进行物理化学的表征检测，以及体内、体外实验进行生物学评价，来探究这种新型表面在种植体骨结合中对于骨稳态的影响和具体作用机制。 本研究以水热法作为种植体改性的基本方法，首先对不同溶液浓度、加热温度以及反应时间下的各种掺锂种植体表面形貌进行了探究。通过场发射扫描电子显微镜(Field emission scanning electron microscope，FSEM)观察各种条件下产生的表面形貌，筛选出最佳的种植体表面。随后通过对该表面进行物理化学性能的探究，分析该表面影响骨稳态的可能机制。 在成功构建了掺锂种植体表面的基础上，通过体外细胞实验，证明了骨髓间充质干细胞(Bone marrow mesenchymal stem cell，BMSC)在掺锂种植体表面能够更好的进行增殖和黏附，同时该表面能够提高Runx-2、β-catenin、Collagen I、OCN等成骨相关基因和蛋白的表达。这一实验结果成功地证实了我们所制备的掺锂种植体表面能够通过调控Wnt／β-catenin信号通路来促进BMSCs的成骨向分化。 实验中进一步研究了掺锂的种植体表面对于破骨细胞(Osteoclast)以及骨稳态的影响。通过细胞增殖实验和免疫荧光染色，证实了该表面对于破骨前体细胞增殖具有一定的抑制作用，可以抑制破骨细胞的成熟分化。与此同时，我们进行了实时荧光定量聚合酶链反应(Real time quantitative polymerase chain reaction， RT-qPCR)和免疫印迹试验(Western Blot)等分子生物学检测，发现掺锂种植体表面可以促进BMSCs分泌破骨细胞抑制因子(osteoclastogenesis inhibitory factor， OPG)，通过RANKL／OPG信号轴来调控成骨细胞和破骨细胞之间的相互联系。 最后我们将掺锂的种植体植入动物体内，通过显微CT扫描技术(Micro-CT)以及硬组织切片染色综合评价这一表面在种植体骨结合中的具体作用。体内实验结果证明，和临床上使用的SLA种植体相比，掺锂的种植体表面能够加快种植体骨结合形成，对新生骨的形成有着显著的促进作用。 本研究通过水热法制备了一种新型的种植体表面。体内、外实验均证实掺锂种植体表面可以通过β-catenin／RANKL／OPG信号轴双向调控骨稳态从而促进种植体骨结合的形成。同时在本研究中，将成骨细胞和破骨细胞作为一个系统相互联系起来，为后续研究种植体骨结合的快速建立提供新的理论依据及实验基础。 关键词：种植体骨结合；水热法；骨髓间充质干细胞；破骨细胞； β-catenin／RANKL／OPG信号轴

 More and more patients choose dental implantation as a repair method for oral dentition defects in recent years. Dental implantation could greatly increase the quality of life. However, it also has some unavoidable problems. The general consensus is that the recovering procedure lasts for at least 3 months, which means that the patient needs to wait for a long period of time to acquire the osseointegration between the implant and the newly formed bone. In order to promote implant osseointegration, reduce the impact of osteoporosis and other diseases on implant osseointegration, improve the implant success rate, scholars are committed to modify the implant surface to promote implant osseointegration. In recent years, the outstanding performance of lithium in osteogenic activities has attracted the attention of scholars. Lithium is one of the main drugs for the treatment of mental diseases such as mania. Some researchers have found that taking lithium-containing drugs could increase the bone density in patients. In this study, a new lithium incorporated surface was prepared by hydrothermal method on the sandblasted, large-grit and acid-etched surface. In vivo and in vitro experiments were taken to explore the effect of this surface on bone homeostasis in implant osseointegration and its possible mechanism. In this study, hydrothermal method was used for surface modification. Firstly, various lithium incoiporated implants were prepared at different concentrations, temperatures and time. Then field emission scanning electron microscopy (FSEM) was used to observe the surface. The best surface was evaluated and chosen. The potential mechanism of the surface affecting bone homeostasis was then analyzed by exploring the physicochemical properties of the surface. On the basis of the successful construction of lithium incorporated implant, it was confirmed by in vitro experiments that the surface of the lithium incorporated implant could promote the proliferation and adhesion of bone marrow mesenchymal stem cells (BMSCs). It also could improve the expression of osteogenic related genes and proteins such as Runx-2, β-catenin, Collagen I and OCN. This result suggested that the lithium incorporated surface could affect the osteogenic differentiation of BMSCs by regulating the Wnt/β-catenin signaling pathway. Furthermore, the effect of the surface on osteoclast was investigated in the experiment. It was confirmed that the lithium incorporated surface has an inhibitory effect on the proliferation of osteoclast precursor cells, and could inhibit the mature differentiation of osteoclasts through the cell proliferation experiments and immunofluorescence staining. In the meantime, Real time quantitative polymerase chain reaction (RT-qPCR) and Western blot detection showed that the surface could promote the secretion of osteoclastogenesis inhibitory factor (OPG) by osteoblasts, and regulated the interrelationship between osteoblasts and osteoclasts through the RANKL/OPG signal axis. Finally, we implanted the lithium incorporated surface into the animals. Micro-CT and hard tissue sections were used to evaluate the effect of this surface in implant osseointegration. The experimental results showed that the surface could accelerate the formation of osseointegration compared with SLA surface, and promote the formation of new bone. In this study, a new implant surface was prepared by hydrothermal method. The results of in vitro and in vivo experiments have confirmed that the lithium incorporated implant surface could regulate bone homeostasis through the β-catenin/RANKL/OPG signal axis, and connect the relationship between osteoblasts and osteoclasts. This new lithium incorporated implants could provide theoretical basis and novel strategies for rapid osseointegration. Key words: implant osseointegration; hydrothermal method; bone marrow mesenchymal stem cells; osteoclast; β-catenin/RANKL/OPG signal axis