| With the development of dental implant technology, implant placement has becomethe routine restorative methods for the edentulous patients. However, with the widespreadof dental implant technology, a variety of risk factors appears to increase the difficulty ofdental implant and therefore constraints its development to some extent. As a risk factorfor dental implant, Diabetes mellitus (DM) patients have high failure rates in implantrestoration, and in recent years, the incidence of diabetes is increasing year by year.NowChina has become the first largest diabetes population country in the world, and themajority of which is type2diabetes.Therefore, relative research into diabetes implant hasbecome the hotspots and difficulty in the fields of dental implant. Although there are lotsof researches about type2diabetes implant, but the mechanism about how it impact the osseointegration is not clear.HbA1C has always been regarded as the golden standard to measure the bloodglucose control of diabetes, but recent studies have found that it cannot fully reflect theactual level of the blood sugar, fluctuations of blood glucose is often overlooked.Fluctuations of blood glucose has been confirmed to play an important role in a variety ofcomplications of diabetes, and its role on the complications of diabetic vascular is evenhigher than that of persistent hyperglycemia, but there is no research about glucosefluctuations in related areas of diabetic implant. Therefore, based on the fluctuations ofblood sugar, this experiment was to explore the impact of blood glucose fluctuations onimplants osseointegration through rat model, while the osteoblasts driven from type2diabetes patients were cultured in different medium with blood glucose fluctuations orpersistent hyperglycemia to explore the role of blood glucose fluctuation on osteoblasts.Through a series of studies, the experiment aimed to confirm the fluctuations of bloodsugar would affect the implants osseointegration, and it would provide new entry pointsand ideas about the mechanism of diabetes on osseointegration.The main methods and results in this study are as follows:Experiment one: Constructed type2diabetes and blood glucose fluctuations animalmodel24male SD rats of pathogen-free were divided into three groups randomly, the firstgroup fed with normal diet served as controls, another two groups of rats were fed withhigh-fat and high-sugar diet in the first3weeks, resulting in insulin resistance in rats andthen were intraperitoneally injected with30mg/kg of streptozotocin(STZ) to make type2diabetic rats model.3days following the STZ injections, rats with blood glucose levels of≥16.0mmol/L were considered diabetic. One group of diabetic rats were allowed tocontinue to feed on a high-fat diet. The blood glucose was monitored, results indicate thatthe rats show stable hyperglycemic state, blood sugar levels within different time points nostatistical significant differences (P>0.05), and this group was considered to be thepersistent hyperglycemia group. The diet of rats in another type2diabetes model groupwas controlled, rats were fasted from19:00to7:00am of the next day for12hours, and then they were given diet with high fat and high sugar food, daily blood glucose in ratswas made fluctuated by us. The monitoring of blood glucose showed that the bloodglucose of rats fluctuated largely, blood sugar levels at different time points hadstatistically significant differences (P<0.05). Comparing with persistent hyperglycemiarats, daily blood glucose fluctuations had statistically significant differences (P<0.05), andthis group was considered to be blood glucose fluctuation group. So the persistenthyperglycemia animal model and the blood glucose fluctuation model of type2diabeteswere established, which provided animal carriers for the following experiments.Experiment two: comparative analysis of the impact on rat peri-implant bonebetween persistent high blood sugar and blood sugar fluctuationsUnder the same operation environment, the implant holes were prepared in the righttibia bone of all the24rats from3groups in experiment one, and the titanium implantswere planted into the holes. After4weeks and8weeks, sacrificed the animals andharvested the tibias containing implants, and made undecalcified tissue slices, stained withponceau trichrome to compare the osseointegration, taken the BIC (bone implant contactpercentage) as the index of osseointegration. we observed conditions of peri-implantunder fluorescence microscope and used image software to measure and calculate theimplant-bone contact ratio (BIC), the data were statistically analyzed. The results showedthat,4weeks after operation, the conditions of the bone around implants betweenpersistent high blood glucose group and blood glucose fluctuation group were similar, BICshowed no significant difference (P>0.05), and was lower than that in normal controlgroup (P <0.05);8weeks after operation, osseointegration of blood glucose fluctuationgroup is worse than the persistent hyperglycemia group, BIC showed significantdifference between the3groups (P <0.05).Experiment three: the impact of different concentrations of glucose cultivation to theproliferation and differentiation of osteoblasts in type2diabetes rat.Sacrificed the animals and harvested the type2diabetic rats tibia, cultivate the ratosteoblast by multiple digestion method, and take the third generation to experiment.Cells were divided into two groups, cultured in hyperglycemia medium and alternating high sugar concentration medium respectively to observe the growth of the cells, to drawthe growth curve, to determine and compare the alkaline phosphatase activity in the twogroups of rats. The results show that cell growth in the hyperglycemia concentration grouppeaked on the6day, but the cell proliferation of fluctuations in sugar concentration groupwas significantly slower (P <0.05), and alkaline phosphatase activity was significantlylower than the hyperglycemia concentration group.conclusion(1)The experiment has once again proven that implant osteointegration in type2diabetic rats is worse than normal rats, there are lots of soft tissues around the implant ofdiabetic rats, and it will impact the combination of implant and bone.(2)The fluctuations of blood sugar will impact the implant osteointegration greaterthan the persistent hyperglycemia of type2diabetic rats,and blood sugar fluctuationsrats need a longer healing time.(3) The proliferation and distribution of osteoblasts cultivated in alternating highsugar concentration medium are poorer than that of hyperglycemia medium, indicatingthat, compared with sustained hyperglycemia of type2diabetes rats, the osteoblastsdamage caused by blood glucose fluctuations is bigger, and blood sugar fluctuations maybe affect the bone around implant through toxic effects.(4) Through the dual authentication of animal experiments and vitro experiments, thisstudy generally confirmed the conjecture about the impact of blood glucose fluctuationson osseointegration in type2diabetic rats before the experiments, proposed a possibleinfluencing factors to lay the foundation for the subsequent further study, as well asprovided new clues for the mechanism about how diabetes influences osseointegration. |
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