Low-intensity pulsed ultrasound exposure has been shown clinically to shorten the fracture repair process and to induce healing of nonunions in humans, but its mechanism of action remains unclear. In this study we investigated the effect and mechanism of low-intensity pulsed ultrasound on nonunion fracture healing in rat tibias. A consistently reproducible nonunion was produced in rat tibias by muscle interposition without osteotomy. This model was produced by creating a closed tibial fracture with only the distal end of the tibialis anterior muscle interposed into the fracture site. One limb was noninvasively exposed to low-intensity pulsed ultrasound (a 200-millisecond burst of sine waves of 1.5 MHz, repeating at 1.0 kHz) for 20 minutes daily. The incident intensity was approximately 30 mW/cm2. Rats were killed at intervals between 2 and 6 weeks. The events were assessed by radiographs, microfocus X-ray computed tomograms, and histologic examination. After 6 weeks of exposure, 7 of 14 nonunion fractures showed healing on radiologic assessment. The results of three-dimensional microfocus X-ray computed tomographic reconstruction and histologic examination also supported this finding. On the other hand, all control tibias remained in a state of nonunion during the same period. These results indicate that low-intensity pulsed ultrasound promotes healing in the rat nonunion fracture model.
In the United States, demineralized bone matrix (DBM) is considered a transplantable tissue and therefore is regulated primarily by the American Association of Tissue Banks. Even though DBM is not subjected to the same regulations relative to performance claims as medical devices are, one would expect different processing methods might yield DBM preparations of different osteoinductive potential. The purpose of this study was to use an established athymic rat model to compare the osteoinductive properties of two commercially available human DBMs prepared using different methods but having essentially identical product claims. Sixteen female athymic rats were used to test equivalent volumes of two lots each of Grafton Putty (Osteotech, Inc., Eatontown, NJ), Osteofil (Regeneration Technologies, Inc., Alachua, FL), and rat DBM. At 28 days after implantation, qualitative and semiquantitative microscopy showed no significant differences in bone formation between the two lots from each source, but rat DBM produced significantly more bone than Grafton, which produced significantly more bone than Osteofil. Our results suggest that methods of graft processing may represent a greater source of variability than do differences among individual donors. Whether these differences relate to methods of demineralization, carrier, dose of DBM per volume, or to some other factor remains to be determined.
Early implant instability has been proposed as a critical factor in the onset and progression of aseptic loosening and periprosthetic osteolysis in total joint arthroplasties. Previous in vitro studies have reported that macrophages stimulated with cyclic mechanical strain release inflammatory mediators. Little is known, however, about the response of these cells to mechanical strain with particles, which is often a component of the physical environment of the cell. We therefore studied the production of prostaglandin E(2) (PGE(2)), an important mediator in aseptic loosening and periprosthetic osteolysis in total joint arthroplasties, for human macrophages treated with mechanical stretch alone, titanium particles alone, and mechanical stretch and particles combined. A combination of mechanical stretch and titanium particles resulted in a statistically synergistic elevation of levels of PGE(2) compared with the levels found with either stretch or particles alone. Exposure of human macrophages to mechanical stretch with particles upregulated the expression of cyclooxygenase (COX)-2 mRNA but not COX-1 mRNA, this expression resulting in a 97-fold increase in PGE(2) production compared to the nonstimulated cells. The current study is the first to investigate the effects of mechanical stretch with particles on cultured macrophages and include an investigation of the time course of PGE(2) production and COX-2 mRNA expression. Our results suggest that, while mechanical strain may be one of the primary factors responsible for macrophage activation and periprosthetic osteolysis, mechanical strain with particles load may contribute significantly to the osteolytic potential of macrophages in vitro. The synergistic effect observed between mechanical stretch and particles could accelerate implant loosening and implies that reduction in either cyclic mechanical strain or wear debris load would lead to a reduction of osteolysis.
Mean viable bone area within 11 retrieved, human titanium mesh cages was approximately 31%. Seams of fibrocartilage within the cages may represent tissue differentiation in response to bending or compressive load.
To our knowledge, these cases are among the first published reports of human histology after vertebral cement augmentation and have implications concerning the nature of the surgical procedures as well as the material used for injection.
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