An experimental study in accelerating bone growth by sustained release of rhBMP-2 nanoparticles during mandibular distraction osteogenesis in rabbits

PURPOSE:To prepare new pharmaceutical forms with sustained release properties of rhBMP-2 poly-butylcyanoacrylate nanoparticles and investigate their drug release characteristics in vitro,and to study the accelerative effect of bone regeneration by locally applied rhBMP-2 nanoparticles during mandibular distraction osteogenesis(DO) in rabbits.METHODS:The rhBMP-2 nanoparticles were prepared by emulsion polymerization method.18 New Zealand white rabbits were randomly divided into two groups and their mandibles were distracted to 6mm at the speed of 0.5mm/12h using a submandibular external distractor.From the first day of distraction,the experimental rabbits were injected with rhBMP-2 nanoparticles in distracted area for 10 consecutive days.Non-rhBMP-2 nanoparticles was injected in the control group.Three rabbits were sacrificed in each group at 1,3,6 weeks after the completion of distraction for serum osteocalcin and ALP activity detection.The mandibles were resected and the new bone was assessed by radiography,histology,measurement of the bone mineral density(BMD) .Biomechanical studies were carried out to determine the stiffness of the regenerated bone.SPSS 11.0 software package and Student's t test were used for statistical analysis.RESULTS:The nanoparticles had smooth morphology and narrow size distribution under scanning electron microscopic observation.The drug encapsulation efficiency was 78%.The rhBMP-2-releasing profiles in vitro showed that rhBMP-2 release could be maintained for more than 10 days.At 6 weeks after the completion of distraction,the formation rate of new bone and the density of the regenerated bone trabeculae of the rabbits treated by rhBMP-2 nanoparticles were superior to those of the control group.The result of mandible BMD test in the experimental group was(0.719±0.004) g/cm2,(0.564±0.020) g/cm2 was in the control group,P0.01;and the results of mandible three-point bending test in the experimental group was(92.143±10.795) N/mm,(55.266±0.774) N/mm was in the control group,P0.05.CONCLUSIONS:The rhBMP-2 nanoparticles have excellent pharmaceutical properties showing sustained release effect with good biological activity.They can accelerate bone formation and maturation during mandibular DO in rabbits.