Microbubble Injection Enhances Inhibition Of LIPUS On Debris-induced Periprosthetic Osteolysis In Rabbit Model

Purpose:Periprosthetic osteolysis with the formation of a synovial-like interface membrane is the leading cause of aseptic prosthesis loosening. Previous studies demonstrated that low-intensity pulsed ultrasound (LIPUS) inhibited the progress of debris-induced periprosthetic osteolysis in vivo. We determined whether the addition of microbubbles would promote the enhancement of LIPUS on bone-implant integration in an early stage osteolysis model.Methods:24male New Zealand white rabbits (48femora) were randomly devided into four groups:Control Group/GCon, Ti Group/GTi, Ti-Us Group/GTi-Us, Ti-Us-Mb Group/GTi-us-Mb.Titanium cylinders were press-fitted into the femoral medullary canals of New Zealand rabbits to set up the periprosthetic osteolysis model. The GTi canals received injection of titanium particles before implantation while the GCon received saline. Before ultrasonic therapy, the GTi-us and the GTi-us-Mb received intra-articular0.3mL saline and microbubble injections, respectively. After6weeks, spicemen were obtained and underwent periprosthetic bone mineral density test, biomechanical evaluation and histomorphometric analysis. Results:Biomechanical testing revealed that GTi-Us-Mb had significantly greater fixation strength than GTi-Us (417.33vs295.17N, p<0.001). No significant difference in bone mineral density was evident in the proximal periprosthetic area. Distal periprosthetic bone mineral density in GTi-us-Mb was almost equivalent to that of GTi-Us (0.32±0.03vs0.31±0.02g/cm2, p=0.913) after the administration of microbubbles. Histomorphometric analyses revealed that increased bone-implant contact (38.13±3.69vs29.95±8.02%, p=0.144), trabecular thickness (0.15±0.03vs0.13±0.02mm, p<0.001), bone area per total area in the near (54.21±7.23vs49.24±7.52%, p=0.636) and far (40.76±8.06vs29.15±6.44%, p=0.020) zone around the implant of GTi-us were further elevated by the addition of microbubbles in GTi-Us-Mb.Conclusions:Taken together, our data demonstrated that microbubble injection enhanced the inhibitory effect of LIPUS on debris-induced osteolysis and further strengthened the mechanical fixation of implants in an early stage osteolysis model in vivo.