Controlled release of paclitaxel using a drug-eluting stent through modulation of the size of drug particles in vivo.

Drug-eluting stents (DESs) are generally used in percutaneous coronary intervention. Paclitaxel (PTX) is widely used in DESs to suppress neointima, which causes restenosis. However, the PTX release profile is slow owing to its hydrophobic properties, resulting in negative effects on re-endothelialization in vessels. In this study, we assessed the effects of the controlled release of PTX particles of specific sizes on in-stent restenosis (ISR). PTX particle sizes were controlled by adjusting the evaporating temperature of the solvent from 25 to 80°C during ultrasonic coating, and DESs were prepared. The properties of prepared films and DESs were analyzed, and cell viability was assessed in vitro and in vivo. Poly(lactic-co-glycolic acid) (PLGA)/PTX500-loaded stents showed the most rapid release for 58 days, and smaller drug particles exhibited lower PTX release rates. In vivo, PLGA/PTX50-, PLGA/PTX250-, and PLGA/PTX500-loaded stents showed good efficacy for alleviating ISR as compared with bare metal stents and PLGA/PTX5-loaded stents. However, PLGA/PTX250- and PLGA/PTX500-loaded stents exhibited strut exposure and reduced recovery of the vascular compared with PLGA/PTX50-loaded stents. PTX drug particles of approximately 50 nm were most effective in vivo, and the control of particle size is a promising strategy for improving the performance of PTX-eluting stents. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2275-2283, 2018.

Effects of Different Implant Osteotomy Preparation Sizes on Implant Stability and Bone Response in the Minipig Mandible.

PURPOSE: The purpose of this study was to investigate the influence of implant and drill diameters on the stability of implant and bone response. MATERIALS AND METHODS: An implant (GS II, Osstem Implant) with a 3.5-mm diameter and drills with three different diameters, differentiating the volume of bone compacted by the implant, were used in this study. Measurement of the insertion torque and observation of bone compression patterns were done during implant site preparation in minipigs. Also, analysis of resonance frequency, histomorphology, marginal bone resorption, and new bone formation were performed. RESULTS: Microstrains and microcracks occurred in cortical bone around the thread when a drill with a smaller diameter than that of the thread was used. Higher implant stability was shown and maintained when a small-diameter drill was used. When using a drill with a smaller diameter than the root diameter of the implant thread, the bone-to-implant contact/bone area (BIC/BA) was higher than the wider drill during the whole test period. However, the use of a wide drill was the most rapid in increasing the BIC/BA value by new bone formation. In the cancellous bone, the speed of new bone formation was not different in each test group. However, the formation of new bone was faster when a large-diameter drill was used in the cortical bone. There was no significant difference in marginal bone loss (MBL) according to drill diameters, but the speed of MBL was fast when using a drill that was smaller than the root diameter of the implant thread. CONCLUSION: Implant stability, BIC, and BA were high when using a final drill that was smaller than the root diameter of the implant thread compared with a wide final drill. However, the speed of new bone formation was relatively slow and the speed of MBL was relatively fast if the final drill was excessively smaller.

Evaluation of the osteogenic activity of the BMP-2 mimetic peptide, PEP7, in vitro and in vivo.

PURPOSE: To evaluate the osteogenic activity of a novel synthetic peptide, PEP7, derived from bone morphogenetic protein 2 (BMP-2) on MG-63, a human osteoblast-like cell line, and on new bone formation in vivo. MATERIALS AND METHODS: The novel synthetic peptide was synthesized by a standard Fmoc method and purified to 98% purity. Cell adhesion, proliferation, and differentiation of MG-63 were observed in the presence of different concentrations of PEP7. Eight micropigs were used to evaluate new bone formation in a supra-alveolar peri-implant defect model. The PEP7-coated implants were randomly allocated to mandible defect sites. The animals were sacrificed after 8 weeks for histologic analysis. RESULTS: PEP7 affected an early stage of adhesion and dose-dependently stimulated differentiation of MG-63 cells. The cell adhesion rate in the group coated with 1 µM PEP7 increased approximately 47% compared to the uncoated group and 32% compared to the group coated with recombinant human bone morphogenetic protein 2 (rhBMP-2) (P < .05). The alkaline phosphatase activities of groups treated with 50 µM of PEP7 were higher than for the other groups. PEP7 induced production of osteoblast-specific proteins in MG-63 cells. The largest effect was caused by 50 µM PEP7, followed by the groups treated with 20 µM synthetic peptide and 10 ng/mL rhBMP-2 (P < .05). CONCLUSIONS: A novel synthetic peptide derived from BMP-2 has osteoinductivity and new bone formation effects, including vertical augmentation of the alveolar ridge.

Effect of microthreads on removal torque and bone-to-implant contact: an experimental study in miniature pigs.

PURPOSE: The objective of this study was to evaluate the effect of microthreads on removal torque and bone-to-implant contact (BIC). METHODS: Twelve miniature pigs for each experiment, a total of 24 animals, were used. In the removal torque analysis, each animal received 2 types of implants in each tibia, which were treated with sandblasting and acid etching but with or without microthreads at the marginal portion. The animals were sacrificed after 4, 8, or 12 weeks of healing. Each subgroup consisted of 4 animals, and the tibias were extracted and removal torque was measured. In the BIC analysis, each animal received 3 types of implants. Two types of implants were used for the removal torque test and another type of implant served as the control. The BIC experiment was conducted in the mandible of the animals. The P1-M1 teeth were extracted, and after a 4-month healing period, 3 each of the 2 types of implants were placed, with one type on each side of the mandible, for a total of 6 implants per animal. The animals were sacrificed after a 2-, 4-, or 8-week healing period. Each subgroup consisted of 4 animals. The mandibles were extracted, specimens were processed, and BIC was analyzed. RESULTS: No significant difference in removal torque value or BIC was found between implants with and without microthreads. The removal torque value increased between 4 and 8 weeks of healing for both types of implants, but there was no significant difference between 8 and 12 weeks. The percentage of BIC increased between 2 and 4 weeks for all types of implants, but there was no significant difference between 4 and 8 weeks. CONCLUSIONS: The existence of microthreads was not a significant factor in mechanical and histological stability.

Experimental study of bone response to hydroxyapatite coating implants: bone-implant contact and removal torque test.

OBJECTIVE: The objective of this study was to evaluate the early osseointegration of hydroxyapatite (HA)-coated implant. STUDY DESIGN: Twelve adult male miniature pigs were used in this study. The removal torque of implants placed in the tibia of miniature pigs was measured. For implants placed in the mandible, histomorphometric evaluation was performed for the evaluation of the bone-implant contact (BIC) ratio. RESULTS: After 4, 8, and 12 weeks, removal torque values were increased. Among the 3 groups, the HA-coated group showed the highest values (P < .05). At 4 and 8 weeks, the BIC ratio of HA was significantly higher than that of resorbable blast medium or sand blasted with alumina and acid etched (P < .05). CONCLUSIONS: It was concluded that HA-coated implants are relatively favorable in early loading stages.

Effect of implant drill characteristics on heat generation in osteotomy sites: a pilot study.

OBJECTIVES: The objective of this study was to evaluate the effect of drill-bone contact area on bone temperature during osteotomy preparation. MATERIAL AND METHODS: Conventional triflute Ø3.6 mm drills were modified with the intent to reduce frictional heat induction. The peripheral dimensions of the drill were reduced 0.15, 0.35 and 0.5 mm to evaluate the effect of surface area on induction of frictional heat between the drill and bone/cutting debris (parameter A). Also, the lateral cutting surface of the drill was set to 0.1, 2 and 7.5 mm to estimate heat induced by direct function of the drill (parameter B). A non-modified triflute drill (parameter A: 0 mm; parameter B: 15 mm) served as control. Thus, nine drills with different A/B combinations vs. one control were tested in artificial bone. Real-time temperature changes (during drilling and withdrawing) were assessed using an infrared thermal imager. Each drilling procedure was performed up to 20 times. Thermal image data were transferred to a PC for simultaneous analysis. RESULTS: Mean temperature changes for all modified drill combinations were smaller than for the control (P<0.001). The effects of parameters A and B were statistically significant (P<0.001). There was a significant interaction effect between the two parameters (P<0.001) showing that the effect of parameter A on the mean temperature changes is different depending on the values of parameter B. As the dimensions of parameter B decreased, the temperature change during drilling also decreased. However, a tendency for the temperature to increase or decrease by parameter A was not observed. CONCLUSIONS: Within the limitations of this pilot study, the observations herein suggest that reduction in contact area between the drill and bone reduces heat induction. Further studies to optimize drill/bone contact dimensions are needed.

Surface properties of endosseous dental implants after NdYAG and CO2 laser treatment at various energies.

OBJECTIVES: Dental lasers have been used for uncovering submerged implants as well as decontaminating implant surfaces when treating peri-implantitis. The objective of this study was to compare the possible alterations of the smooth surface and resorbable blast material (RBM) surface implants after using NdYAG and CO(2) lasers at various energies. MATERIALS AND METHODS: Ten smooth surface implants and 10 RBM surface implants were used. Two smooth surface implants and 2 RBM surface implants served as a control group that was not lased. The remaining implants were treated using NdYAG and CO(2) lasers. The surface of each implant was treated for 10 seconds on the second and third threads. The smooth surface implants (group 1) were treated using a pulsed contact NdYAG laser at power settings of 1, 2, 3.5, and 5 W, which are commonly used for soft tissue surgery; the corresponding energy and frequency were 50 mJ and 20 Hz, 100 mJ and 20 Hz, 350 mJ and 10 Hz, and 250 mJ and 20 Hz, respectively. The group 2 RBM implants were treated using a pulsed contact NdYAG laser. The group 3 smooth surface implants were treated using a pulsed wave non-contact CO(2) laser at 1, 2, 3.5, and 5 W, and the group 4 RBM implants were treated using a pulsed wave non-contact CO(2) laser. Data were analyzed using scanning electron microscopy. RESULTS: The control surface was very regular and smooth. After NdYAG laser treatment, the implant surface showed alterations of all the surfaces. The amount of damage was proportional to the power. A remarkable finding was the similarity of the lased areas on the smooth and RBM surfaces. CO(2) laser at power settings of 1.0 or 2.0 W did not alter the implant surface, regardless of implant type. At settings of 3.5 and 5 W, there was destruction of the micromachined groove and gas formation. CONCLUSION: This study supports that CO(2) laser treatment appears more useful than NdYAG laser treatment and CO(2) laser does not damage titanium implant surface, which should be of value when uncovering submerged implants and treating peri-implantitis.