Objective: To study the effect of gastrodin on oxidative stress and bone tissue around implants in type 2 diabetes mellitus rats (T2DM), so as to provide therapeutic basis for the problems of poor osseointegration and long repair period of implants in type 2 diabetic patients, to provide the basis for the development of new therapeutic drugs. Methods: Forty SD rats aged 5 weeks were divided into control group (n=10) and model group (n=30). The model group was fed with high glycolipid diet for 4 weeks and injected with 35 mg/kg streptozocin. The T2DM were divided into diabetic group (n=10) and gastrodin group (n=10). Pure screw titanium implants were placed in the metaphysis of both tibia. Rats in gastrodin group were given gastrodin 13.6 mg/kg everyday, while the control group and diabetic group were given the same dose of saline solution. Blood glucose was measured every two weeks after operation in all rats. After 4 and 8 weeks, the contents of serum malondialdehyde (MDA) and superoxide dismutase (SOD) were measured to analyze the oxidative stress level in rats. The expression of anti-apoptosis protein [B cell lymphoma/lewkmia-2 (bcl-2)]and apoptosis protein [bcl-2-associated X protein (bax)] was analyzed by immunohistochemistry. HE staining and micro-CT scanning were used to analyze the osseointegration around the implants. Results: The blood glucose of gastrodin [(12.98±2.53), (13.64±1.96), (14.58±3.40) and (12.84±2.82) mmol/L] were significantly lower than that of diabetic group [(20.97±2.27), (17.94±3.76), (23.66±2.90) and (21.22±2.67) mmol/L] at corresponding time point (P<0.017). Four and 8 weeks following surgery, the MDA concentration in gastrodin group [(5.21±1.60) and (3.47±1.17) nmol/ml] was significantly lower than that in diabetic group [(11.42±5.11) and (7.31±1.37) nmol/ml] at the corresponding time points (P<0.017), while SOD activity in gastrodin group [(42.89±6.00) and (53.12±9.73) U/ml] was significantly higher than those in diabetic group [(27.09±6.11) and (32.08±2.97) U/ml] at the corresponding time points (P<0.017). Immunohistochemistry showed that the bcl-2 expression in gastrodin group was significantly higher than that in diabetic group at 4 and 8 weeks following surgery (P<0.017), while the bax expression in gastrodin group was significantly lower than that in diabetic group (P<0.017). Four weeks after surgery, the bone volume/tissue volume (BV/TV), connection density (Conn.D), trabecular number (Tb.N), trabecular thickness (Tb.Th) in gastrodin group were significantly higher than those in diabetic group (P<0.017). There was no significant difference in trabecular separation/spacing (Tb.sp) between gastrodin group and diabetic group (P<0.017). Eight weeks after surgery, the BV/TV, Tb.N in gastrodin group were significantly higher than those in the diabetic group (P<0.017). There was no significant difference in Conn.D between gastrodin group and diabetic group (P<0.017). There was no significant difference in Tb.Th and Tb.sp in three groups (P<0.017). The trabecular structure in gastrodin group was better than that in diabetic group by HE staining. Conclusions: Gastrodin can decrease blood glucose, improve oxidative stress, protect bone tissue from apoptosis and promote bone formation around implants in T2DM.
Animals ; Benzyl Alcohols ; Blood Glucose ; Dental Implants ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 2 ; Glucosides ; Proto-Oncogene Proteins c-bcl-2 ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; Tibia ; bcl-2-Associated X Protein

Microarc oxidation (MAO) has become a promising technique for the surface modification of implants. Therefore, the aims of this study were to further quantitatively and qualitatively evaluate the osteointegration abilities of MAO-treated and smooth surface (SF) implants in vivo and to investigate the areas in which the superiority of MAO-treated implants are displayed. In a rabbit model, a comprehensive histomorphological, osteogenic, mineralizational, and integrative assessment was performed using light microscopy, fluorescence microscopy, confocal laser scanning microscopy, and radiographic analyses. Compared with the SF groups, the MAO-treated groups exhibited more active contact osteogenesis, as well as distant osteogenesis, under fluorescence examination, the mineral apposition rate was found to be greater for all of the MAO-treated implants, and the osteointegration index (OI) value was greater in the MAO-treated groups at different times. In conclusion, the calcium-rich amorphous layer created by MAO provided a better environment for osteointegration, with more active contact osteogenesis, a more rapid mineral apposition rate and greater OI values.
Animals ; Bone-Implant Interface ; physiology ; Dental Implantation, Endosseous ; methods ; Dental Implants ; Femur ; surgery ; Implants, Experimental ; Materials Testing ; Microscopy, Confocal ; Microscopy, Electron, Scanning ; Microscopy, Fluorescence ; Models, Animal ; Osseointegration ; physiology ; Oxidation-Reduction ; Rabbits ; Spectrometry, X-Ray Emission ; Surface Properties ; Titanium

The objective of this study is to examine the effect of low-magnitude, high-frequency (LMHF) loading, and anti-osteoporosis medications such as parathyroid hormone (PTH) and bisphosphonates on peri-implant bone healing in an osteoporosis model, and to assess their combined effects on these processes. Thirteen-week-old ovariectomized rats (n = 44) were divided into three groups: PTH, alendronate, and saline. After 3 weeks of drug administration, titanium implants were inserted into the tibiae. Each group was subdivided into two groups: with or without LMHF loading via whole-body vibration (50 Hz at 0.5 g, 15 min per day, 5 days per week). Rats were killed 4 weeks following implantation. Removal torque test, micro-CT analyses (relative gray (RG) value, water = 0, and implant = 100), and histomorphometric analyses (bone-to-implant contact (BIC) and peri-implant bone formation (bone volume/tissue volume (BV/TV))) were performed. Removal torque values and BIC were significantly differed by loading and drug administration (ANOVA). Post hoc analysis showed that PTH-treated groups were significantly higher than the other drug-treated groups. BV/TV was significantly enhanced by PTH administration. In cortical bone, RG values were significantly increased by loading. In trabecular bone, however, RG values were significantly increased by PTH administration. These findings suggest that LMHF loading and PTH can act locally and additively on the bone healing process, improving the condition of implant osseointegration.
Alendronate ; administration & dosage ; pharmacology ; Animals ; Dental Implantation, Endosseous ; methods ; Dental Implants ; Female ; Implants, Experimental ; Osseointegration ; drug effects ; Ovariectomy ; Parathyroid Hormone ; administration & dosage ; pharmacology ; Rats ; Tibia ; surgery ; Vibration ; Wound Healing ; drug effects

PURPOSE: The aim of present investigation was to find out the influence of several times iatrogenic mobilization in the initial stage of implant installation on bone-implant osteointegration. MATERIALS AND METHODS: The experimental implants (3.75 mm in diameter, 8.0 mm in length) were made of commercially pure (Grade IV) titanium, and were treated with RBM (MegaGen(R): Ca-P) on lower 4.0 mm part. Only lower part of implant was inserted to bone and the implants were nonsubmerged. The 130 implants (two in each tibia) were inserted into the monocortical tibias of 33 rabbits which each weighed more than 3.5 kg (Female, New Zealand White). According to the removal torque interval, the groups were divided into 13 groups, group I (1 day), group II (1 day + 2 days), group III (1 day + 2 days + 3 days), group IV (1 day + 2 days + 3 days + 4 days), group V (2 days), group VI (2 days + 4 days), group VII (2 days + 4 days + 6 days), group VIII (2 days + 4 days + 6 days + 8 days), group IX (4 days), group X (4 days + 7 days), group XI (4 days + 7 days + 10 days), group XII (4 days + 7 days + 10 days + 14 days) and control group. In the control group, the removal torque was measured at 8 weeks with a digital torque gauge (Mark-10, USA). In the experimental groups, the removal torque was given once, twice, three times or four times by experiment design before the final removal torque and the value was measured each time. The implants were then screwed back to their original positions. All the experimental groups were given a final healing time of 8 weeks after placement, in which values were compared with the control groups and the 1st, 2nd, 3rd or 4th removal torque values in each experimental group. RESULTS: In comparison of the final removal torque tests among experimental groups, the removal torque value of experimental groups except group XII were not statistically different that of control group. And the values of group I and II were significantly higher than the values of group VI, VIII, X, XI, and XII. In addition, the values of group III, IV, and V were significantly higher than group XI and XII. In comparison of the removal torque in the each experimental group, the final removal torque were significantly higher in all groups except group VIII, X, XI, and XII. CONCLUSION: If sufficient healing time was allowed, a few mobilization of fixture at the very early stage after the implant placement in the rabbits didn't interrupt the final bone to implant osseointegration.
Dental Implants ; Implants, Experimental ; New Zealand ; Osseointegration ; Rabbits ; Tibia ; Titanium ; Torque

PURPOSE: The aim of this study was to investigate the effect of implant thread profile on the marginal bone stresses which develop during implant insertion. MATERIALS AND METHODS: Four experimental implants were created by placing four different thread systems on the body (4.1 mm x 10 mm) of the ITI standard implant. The thread types studied in this study included the buttress, v-shape, reverse buttress, and square shape threads. In order to examine the insertion stress generation, 3D dynamic finite element analysis was performed which simulated the insertion process of implants into a 1.2 mm thick cortical bone plate (containing 3.5 mm pilot hole) using a PC-based DEFORM 3D (ver 6.1, SFTC, Columbus, OH, USA) program. RESULTS: Insertion stresses higher than human cortical bone developed around the implants. The level of insertion stresses was much different depending on the thread. Stress level was lowest near the v-shape thread, and highest near the square shaped thread. Difference in the interfacial bone stress level was more noticeable near the valley than the tip of the threads. CONCLUSION: Among the four threads, the v-shape thread was turned out to minimize the insertion stress level and thereby create better conditions for implant osseointegration.
Bone Plates ; Finite Element Analysis ; Humans ; Implants, Experimental ; Osseointegration

This study was aimed to establish rat bladder tumor animal models to investigate the in viva antitumor effect of polyanhydride-pirarubicin (PAD-THP), a long-lasting anti-cancer implant, in the bladder tumor of animal models. The model of bladder cancer was set up with N-butly-N-(4 hydroxybutyl) nitrosamine (BBN) feeding into rats. The PAD-THP long-acting anti-cancer implants containing the drugs and the same dose of the THP naked drug were placed under the bladder mucosa of bladder tumor model in vivo. The pirarubicin plasma concentration was measured with high performance liquid chromatography (HPLC) detection in vivo. The effective drug concentration and lasting period were observed and compared in the animal bodies. The tumor sizes were measured before and after the treatment. The in viva antitumor effects were analyzed and compared. The results showed that more significant antitumor effect of PAD-THP implants on the local drug release characteristics were presented compared with that of the same dose of THP bare drug group and there were significant differences (P<0. 05) between the two methods. All the results indicated that the PAD-THP anti-cancer implants in the postoperative local treatment of bladder tumors would show prosperous in the future for clinical application.
Animals ; Antineoplastic Agents ; administration & dosage ; Butylhydroxybutylnitrosamine ; Delayed-Action Preparations ; administration & dosage ; Disease Models, Animal ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Female ; Implants, Experimental ; Polyanhydrides ; administration & dosage ; Rats ; Rats, Sprague-Dawley ; Urinary Bladder Neoplasms ; chemically induced ; drug therapy ; pathology

To evaluate the biological safety of collagen-based bone repairing material, we implanted the sample or reference substance into rats, and observed relative signs, including the specific inspection targets in animals, blood examination, analysis of immune organ, the pathological examination of organs and tissues, NK cell killing activity assay, lymphocyte group analysis, serum IL-1, IL-6, TNF-alpha detection, detection of immune globulin. Meanwhile, we set control group, sham group, and immunosuppression group. The final results showed that there was no abnormal mental state before and after the experiment. Compared with the control group, the tested group indicated no significant difference in blood test, immune organ analysis, the pathological examination of organs and tissues, NK cell killing activity assay, lymphocyte subset analysis serum IL-1, IL-6, TNF-alphadetection, and detection of immune globulin. Collagen-based bone repairing material produced a slight and transient stimulation on the rats, but created no significant inflammatory responses.
Absorbable Implants ; Animals ; Bone Matrix ; physiology ; transplantation ; Bone Regeneration ; Bone Substitutes ; Collagen ; chemistry ; Implants, Experimental ; Materials Testing ; Prostheses and Implants ; Rats

PURPOSE: The purpose of this study was to investigate the influence of mobilization on bone-implant interface prior to osseointegration of fixtures. MATERIALS AND METHODS: The experimental implants (3.75 mm in diameter, 4.0 mm in length) were made of commercially pure (Grade IV) titanium, and were treated with RBM (MegaGen(R): Ca-P). The 80 implants (two in each tibia) were inserted into the monocortical tibias of 20 rabbits which each weighed more than 3.5 kg (Female, New Zealand White). According to the removal torque interval, the groups were divided into 10 groups, Group I (6 wks), Group II (4 days + 6 wks), Group III (4 days + 1 wk + 6 wks), Group IV (1 wk + 6 wks), Group V (1 wk + 1 wk + 6 wks), Group VI (2 wks + 6 wks), Group VII (2 wks+ 1 wk + 6 wk), Group VIII (3 wks + 6 wks), Group IX (3 wks + 1 wk + 6 wks) and Group X (10 wks). The control groups were Group I and X, the removal torque was measured at 6 wks and 10 wks with a digital torque gauge (Mark-10, USA). In the experimental groups, the removal torque was given once or twice before the final removal torque and the value was measured each time. After which, the implants were put back where they had been except the control groups. All the experimental groups were given a final healing time (6 wks) before the final removal torque test, in which values were compared with the control groups and the 1st and/or 2nd removal torque values in each experimental group. RESULTS: In the final removal torque tests, the removal torque value of Group X (10 wks) was higher than that of Group I (6 wks) in the control groups but not statistically different. There were no significant differences between the experimental groups and control groups (P>.05). In the first removal torque comparison, the experimental groups (4 days or 1 wk) values were significantly lower than the other experimental groups (2 wks or 3 wks). In the comparison of each experimental group according to healing time, the final removal torque value was significantly higher than the 1st torque test value. CONCLUSION: Once or twice mobilization of fixture prior to osseointegration did not deter the final bone to implant osseointegration, if sufficient healing time was given.
Implants, Experimental ; New Zealand ; Osseointegration ; Rabbits ; Tibia ; Titanium ; Torque

OBJECTIVETo assess the effect of puerarin, a natural flavonoid found in Chinese Pueraria Lobata (Wild.) Ohwi, on promotion of new bone formation.

METHODSOsteoblasts isolated from calvarial of newborn rats were cultured in vitro in the presence of puerarin at various concentrations. The viability of osteoblasts and alkaline phosphotase activity and mineral node formation were determined. In addition, osteoblasts seeded in the β-tricaclium phosphate scalfolds as bone substitute were implanted in rat dorsal muscles. Half -of the recipient rats received intramuscular injection of puerarin at 10 mg/(kg·d) for 7 days. Osteogenesis was analyzed by examining the histology after 4 weeks of implantation.

RESULTSThe viability of osteoblasts treated with puerarin at either 40 or 80 μmol/L was significantly higher than that of the control (P<0.05 and P<0.01, respectively). Alkaline phosphatase and mineral modules were significantly increased in osteoblasts cultured with puerarin at 40 or 80 mol/L when compared with that of the untreated cells. The puerarin-treated rats had a higher rate of bone formation in the osteoblast implants than the control rats (6.35% vs. 1.32%, respectively, P<0.05).

CONCLUSIONPuerarin was able to affect osteoblast proliferation and differentiation, and promote the new bone formation in osteoblast implants.

Alkaline Phosphatase ; metabolism ; Animals ; Calcification, Physiologic ; drug effects ; Cell Differentiation ; drug effects ; Cell Survival ; drug effects ; Implants, Experimental ; Isoflavones ; pharmacology ; Male ; Microscopy, Electron, Scanning ; Osteoblasts ; cytology ; drug effects ; enzymology ; Osteogenesis ; drug effects ; Rats ; Rats, Sprague-Dawley ; Tissue Scaffolds

According to the requirements of ISO10993-11.2006 and ISO10993-6:r2007 standards, we used SD rats for evaluating the subchronic systemic toxicity and local implantation response of two kinds of sodium hyaluronan gels with different application. The results of 90d subchronic toxicity study by intraperitoneal route showed that the animals of the tested group and control group grew normally. There were no differences in the increases of the body weight, haematological index and clinical biochemistry indexes. The examination of gross pathology and histopathology revealed no abnormal changes caused by the test substance during the process. But there was different degree test article residual in the body of the animals at the end of the experiment. It was observed in the local subcutaneous implantation that at the early stage, gel A had mild inflammatory response, cysts were seen clearly, and new blood capillaries were visible at local area. Later, the wall got thinner and dense with little tissue reaction. Gel B also had mild inflammatory response earlier, but it totally disappeared after 14 days of implantation. It can be concluded that the gel products with different characteristics decided its degradation and metabolic process in the body of the test animals and therefore the areas of application of the products clinically. Meanwhile, we compared the evaluation method of subchronic systemic toxicity and local implantation response in risk assessment, providing reference for the choice of biological safe testing.
Animals ; Female ; Gels ; toxicity ; Hyaluronic Acid ; toxicity ; Implants, Experimental ; Male ; Rats ; Rats, Sprague-Dawley ; Toxicity Tests, Subchronic