Effect And Mechanism Of A Lithium Incorporated Surface On The Osseointegration By Regulating The β-catenin/RANKL/OPG Axis

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 incorporated 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,(3-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.