| Oral implant has become the idea treatment modality for missing teeth and maxillofacial defects,more and more patients whom lost teeth have accept this treatment. However, some systemic disease such as diabetes may affect the osseointegration of implant and lead to a high falure, which was greatly restricted the application of dental implant in these patients. With the rapid development of social economy and transition of peoples'life style in China , the number of patients suffered from diabetes is increasing in a rapid speed year by year, and now China has become the first largest diabetes population country in the world. So how to get a better success rate of dental implant in diabetic patients and popularize the treatment in the larger scale of patients has become a hot topic in the domestic and abroad. Based on the current research situation, in this study we established diabetes animal models, planted impants in the tibia of diabetic rats, and loaded growth factor which could stimulate new bone formation on the surface of implant by a controlled-release system , evaluated the effect on the osseointegration. The purpose of the study is to explore a solution of dealing with high failure rate in the diabetic patients with dental implant, and offer a new thought and theoretical basis to solve the clinical problem.The methods and main results in this study are as follows:1. Successfully constructed diabetes animal implant model with SD rats In this experiment we chose 9-week-old male SD rats, feed them with the high fat-sugar diet for 4 weeks, then gave low doses of STZ injection retroperitoneal. Eventually obtained 20 diabetic rats with stable blood glucose content scope in 19.5±2.5 mmol/L through dynamic monitoring; Through analysis tibia anatomical structure of the rat, we designed a 3.3×6mm cone- shaped pure titanium implant , coarsened the surface of implant with Microarc Oxidation treatment; drilled a hole in the tibia of diabetic rat and inserted the implant into the hole, then the diabete implant model was established.2. Constructed bFGF-PLGA microsphere controlled release systemWe chose biodegradable polymer materials PLGA as the carrier of bFGF, the PLGA loaded bFGF microspheres were prepared using W/O/W double- emulsion solvent evaporation method. SEM was conducted to analyze the morphology of microspheres. The sustained delivering ability of bFGF was tested in vitro, Release kinetics profiles were calculated in terms of cumulative release with incubation time. Experimental results showed that the average size of PLGA microspheres was small and uniform, and the encapsulated ratio of bFGF was about 73.5%, release kinetics test in vitro exhibited that in the first 28 days about 82% of bFGF was released from the PLGA microsphere, it is proven that the bFGF-PLGA microspheres could be achieve an ideal controlled release effect. 3. Local application of bFGF-PLGA around implant in diabetic rats tibialThe 20 diabetic rats were randomly divided into diabetes control group and bFGF intervention group (n=10), meanwhile 10 normal SD rats with same age were selected as the normal control group. The implant holes were prepared in the right tibia bone of all rats, and the MAO surface treated titanium implants were planted into the holes. Simultaneously the previously prepared microspheres were mixed with blood and loaded on the surface of the implant before planted into the sites in the bFGF intervention group. After 4 and 8 weeks, sacrificed the animals and harvested the tibias containing implants, embedded the specimens with resin and made undecalcified tissue slices to compare the osseointegration, taken the BIC (bone implant contact percentage) as the index of osseointegration. Experimental results showed that the implants of the normal control group were surrounded by new lamellar bone with continuity at 4 weeks, whereas the tissue around the implants of the diabetic control group contained little woven bone and some fibrous tissue, and obvious new formed bone with continuity was observed in bFGF intervention group.The situation of bone formation of 3 groups was similar to previous at 8 weeks, but all of the groups have bone mass increase and the maturity was higher.The statistical analysis of BIC at 4weeks showed that in diabetic control group the BIC (44.6%) was significantly less than those in the normal control group (57.4%) and bFGF intervention group (53.7%) (P <0.05); the average BIC in bFGF intervention group was less than the normal control group, but showing no statistically significant difference (P>0.05). At 8 weeks postsurgery, the average BIC in normal control group reached 68.2% and in the bFGF intervention group the number was 63.7%, which were both significantly greater than that of 50.4% in the diabetic control group (P <0.05). ConclusionLocal delivery of bFGF from PLGA controlled release microsphere around titanium implants may improve the osseointegration in type 2 diabetes rats. This study provide a new thought and theoretical basis for solving the problem that oral implants have high risk in type 2 diabetic patients. |
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