Combined Use Of rhBMP-2 And Low Intensity Pulsed Ultrasound To Enhance Bone Healing In Large Defects
Angle, Siddhesh R.
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Fractures account for about 25% of all the musculoskeletal injuries. While most fractures heal, larger segmental bone defects experience delayed healing, and in some cases, result in a non-union if not treated. The goal of this study was to develop a methodology to accelerate the healing of a critical-size segmental bone defect with the aid of exogenously supplied osteotrophic growth factor, rhBMP-2 and a time-controllable application of mechanical stimulus in the form of LIPUS. Infuse® (rhBMP-2) and ExogenTM(LIPUS), autonomously, have received approval from the U.S. FDA for clinical use. As a result, the information from this study can be directly translated into a clinical situation. The study was designed and evaluated keeping in mind the ‘translational’ ability of the potential outcomes. From the results of the study we concluded that rhBMP-2 was effective in bridging and increasing the bone volume in the critical-size defect and exhibits a bi-phasic mode with 12µg being the calculated optimum dose. Although the calculated values cannot be directly translated clinically, it is clear that there is an optimum dose of rhBMP-2, above which and below which less stimulation of bone occurs. When tested out, 12µg of rhBMP-2 did show the maximum volume of bone regenerated in the defect, maximum bridging and highest mechanical strength in resemblance to the native cortical bone. Simultaneous stimulation with LIPUS enhanced these effects via callus maturation at the optimum dose (12μg) and increased bone formation at suboptimum doses (1.2μg and 6μg). LIPUS having had no proven side effect, can be used with lower doses of rhBMP-2 to achieve equally strong regenerated bone. Finally, the use of LIPUS throughout the healing process might not be a dire necessity. It turns out the best phase to use LIPUS to enhance rhBMP-2 induced bone formation is the osteogenic phase (week 3) where if not better, is as good as using LIPUS throughout the healing process. Thus use of LIPUS in combination with a clinically safe dose of rhBMP-2, can enhance the healing process, thereby reducing the recovery time and cost needed to repair a critical-size defect or a non-union by a significant proportion.
SubjectBone Morphogenetic Protein
Low Intensity Pulsed Ultrasound
Date available in INDIGO2012-12-09T20:09:02Z