| With the further development of the implantodontics, dental implant has already become a kind of important repaired method for the missing tooth. The diabetes has been a dangerous factor which influences the implant prosthodontics, several recent years, more and more of diabetic patients request a therapy of the dental implants, majority among them is type 2 diabetes. Therefore, the research of diabetic implantodontics has become and a hot problem at the international studying in the last years. Currently, the main performance of the diabetic implantodontics is the worse osseointegration and a lower success rate of oral implants, but it also is a doubt that the diabetes how to influence the implant osseointegration which caused the higher implant failure rate. How to get a further study on diabetic implantodontics about mechanism and impact factors of the implant osseointegration, and how to increase the implant success rate? It still needs a further research. ObjectIn this experiment, we aimed to stimulate the osteoblast proliferation and differentiation around the implant in type 2 diabetic patients, study to a kind of valid local intervention project, and looking for a method which can effectively ameliorate the state of implant osseointegration. In this study, we planed to prepare a insulin-containing microcapsules by a biodegradable polymer(PLGA), setting up a system which can used to local intervention and sustained release insulin. We delivered insulin from insulin-containing PLGA microcapsules directly to the implant site in a type 2 diabetic rats which the character is similar to type 2 diabetic patients, thereby it can stimulate the osteoblast proliferation and differentiation around the implant and ameliorate the level of implant osseointegration in the diabetic rats, the last the success rate of oral implants can get increased. This study offered a new way of thinking and theories basis for decreasing the oral implant failure rates in clinical practice, it also layed the foundation for solving the problem that oral implants have high risk in type 2 diabetic patients.Methods and resultsThe first part: the establishment of research model by type 2 diabetic ratsTwenty male GK rats, 8 weeks of age, the weight is 250-280 g, The animals were fed with a diet enriched with high fat and high glucose with 3-6 weeks. Blood samples were drawn from the tail vein in diabetic rats to detect the blood glucose; rats that did not match the required index (fasting blood glucose, FBG≥16.7 mmol/L or 300mg/dL) were excluded from this study. Through the research on the form and volume of distal end of tibia of SD rats(8 weeks of age, 250-280 g) was completed, we contrived an titanium implant which was treatment of etching and the size is3.3×6mm, the next step is inserting the implants on the tibia of the type 2 diabetic GK rats. In the whole experiments the blood glucose, weight and the blood insulin level were monitored. The GK rats which the blood glucose is out of the range of 17.0-18.0 mmol/L were excluded from this study, and establish the research model of type 2 diabetic rats. Datas are obtained by SPSS13.0 for Windows and presented as mean values±standard deviation. T-test or separate variance t-test was used to test for a significant effect in the groups. A P value <0.05 was considered statistically significant.Results:(1) In the experiment, almost 80% GK rats expressed much more stabilized state, the blood glucose level was in the range of 18±1.0 mmol/L. The blood glucose in type 2 diabetic rats(17.98±0.37 mmol/L) was higher than that in SD rats(9.41±1.78 mmol/L). A significant difference was observed after separate variance t-test, p<0.05.(2) The hydroposia volume and food-intake in GK rats were higher than that in SD rats, and the urine volume increased transparently.(3) In the experiment, the weight in type 2 diabetic group rats(307.7±6.62 g) was lower than that in SD rats(329.7±6.0 g). A significant difference was observed after t-test, p<0.05.(4) The blood insulin level in type 2 diabetic rats(29.09±4.99 mU/L) was higher than SD rats(9.16±2.16 mU/L),A significant difference was observed after separate variance t-test, p<0.05.The second part: the research of the bone-implant contact rates in type 2 diabetic rats.The type 2 diabetic GK rats were divided into 4 groups (INS1 group, INS2 group and DM1 group, DM1 group). And the SD rats were used as the control group which divided into 2 groups (C1 group and C2 group). The titanium implants were inserted on the tibia of the rats including INS1, INS2, DM1, DM2, C1and C2 groups. Simultaneously, we mixed the previous prepared pulverized microspheres and auto-blood, and loaded them on the surface of the implant before it was inserted in the rats of GK group and the rats in C group were not treated. The microspheres were allowed immediate release directly to the bone around implants. Animals in INS1, DM1 and C1 groups were sacrificed after 2 weeks and the others after 6 weeks. The tibias were dissected, and blocks containing the experimental specimens were obtained, then all sections were stained with modified Masson Trichrome staining. For bone histomorphometry measurements, images were obtained using an image collection system. Datas are obtained by SPSS13.0 for Windows and presented as mean values±standard deviation. One-way ANOVE was used to test for a significant effect in the groups. A P value <0.05 was considered statistically significant.Results:(1) 2 weeks after implantation, the bone-implant contact rates in INS1 group, DM1 group, C1 group were: 50.73±2.80%, 28.82±5.32% and 56.55±4.57%.(2) 6 weeks after implantation, the bone-implant contact rates in INS2 group, DM2 group, C2 group were: 51.46±3.23%, 58.23±3.12% and 66.44±3.56%.(3) 2 weeks after implantation, the bone-implant contact rates in INS1 group were much more higher than that in DM1 group, a significant difference was observed, p<0.01; but it was lower than that in C1 group, a difference was observed, p<0.05;(4) 6 weeks after implantation, the bone-implant contact rates in INS2 group were much more higher than that in DM2 group, a significant difference was observed, p<0.01; but it was lower than that in C2 group, a difference was observed, p<0.01;The third part: the research of the bone tissue around the titanium implants in type 2 diabetic rats.The induced bone density measurements (including osteogen volume, newly formed bone volume, et al.), adjacent to the implant surface and the images were obtained using an image collection system from the second part. Datas are obtained by SPSS13.0 for Windows and presented as mean values±standard deviation. T-test or separate variance t-test was used to test for a significant effect in the groups. A P value <0.05 was considered statistically significant.Results:(1) 2 weeks after implantation, osteogen volume in INS1 group, DM1 group, C1 group were: 28.17±3.83%, 24.18±3.10%, 25.92±2.25%, and the osteoid volume were 30.96±2.44%, 25.97±2.19%, 19.06±2.12%.(2) 6 weeks after implantation, osteogen volume in INS2 group, DM2 group, C2 group were: 45.63±3.05%, 6.59±3.08%, 42.43±4.73%, and the osteoid volume were 30.34±1.80%, 86.80±6.26%, 42.25±2.97%.(3) 2 weeks after implantation, newly formed bone volume in INS1 group(6.32±1.26%) was higher than that in C1 group, but there is no newly formed bone volume appeared in DM1 group.(4) 2 weeks after implantation, osteogen volume in INS1 group was higher than that in DM1 group and C1 group, and there are significant differences, p<0.05.(5) 6 weeks after implantation, osteogen volume in INS2 group was much more higher than that in DM2 group, a difference was found, p<0.01. And a little decrease was observed in C2 group, there is a difference, p< 0.05.Conclusion(1) 80% GK rats were maintained in a much more stabilized state, the blood glucose level was in the range of 18±1.0 mmol/L. The blood insulin level, hydroposia volume, food-intake and the urine volume appeared markedly raise, but the weight was lower than SD rats, these characters were similar to type 2 diabetic patients.(2) 2 weeks after implantation, as the enhancement of the osteoblast proliferation and differentiation around the implant by local insulin intervention released by PLGA microspheres in INS1 group, newly formed bone volume higher than the others, and the bone-implant contact rates and osteogen volume were higher than that in DM1 group and lower in C1 group.(3) 6 weeks after implantation, osteogen volume in INS2 group maintained high level than the others and the bone-implant contact rates were lower than that in C2 group, higher in DM2 group, with the completion of controlled release of insulin.(4) The bone-implant contact level in type 2 diabetic rats could be ameliorated by local insulin intervention, and it just showed a little difference with SD rats. The type 2 diabetic rats could maintain higher osteogen volume in the later period, though the bone-implant contact level was not the best one, it already had enormous increase.
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