Effects of intermittent hydrostatic pressure and BMP-2 on osteoarthritic human chondrocyte metabolism in vitro.

PURPOSE: This study examined effects of intermittent hydrostatic pressure (IHP) and a chondrogenic growth factor, bone morphogenetic protein-2 (BMP-2), on anabolic, catabolic, and other metabolic markers in human osteoarthritic (OA) chondrocytes in vitro. METHODS: Articular chondrocytes, isolated from femoral OA cartilage and maintained in high-density monolayer culture, were examined for effects of BMP-2 and IHP on gene expression of matrix-associated proteins (aggrecan, type II collagen, and SOX9) and catabolic matrix metalloproteinases (MMP-2 and MMP-3) and culture medium levels of the metabolic markers MMP-2, nitric oxide (NO), and glycosaminoglycan (GAG). The results were analyzed using a mixed linear regression model to investigate the effects of load and growth factor concentration. RESULTS: IHP and BMP-2 modulated OA chondrocyte metabolism in accordance with growth factor concentration independently, without evidence of synergism or antagonism. Each type of stimulus acted independently on anabolic matrix gene expression. Type II collagen and SOX9 gene expression were stimulated by both IHP and BMP-2 whereas aggrecan was increased only by BMP-2. IHP exhibited a trend to decrease MMP-2 gene expression as a catabolic marker whereas BMP-2 did not. NO production was increased by addition of BMP-2 and IHP exhibited a trend for increased levels. GAG production was increased by BMP-2. CONCLUSIONS: This study confirmed the hypothesis that human OA chondrocytes respond to a specific type of mechanical load, IHP, through enhanced articular cartilage macromolecule gene expression and that IHP, in combination with a chondrogenic growth factor BMP-2, additively enhanced matrix gene expression without interactive effects.

Intramedullary screw fixation of proximal fifth metatarsal fractures: a biomechanical study.

Intramedullary screw fixation is a popular technique for treatment of proximal fifth metatarsal fractures. The purpose of this study was to compare the fixation rigidity of a 5.5 mm partially threaded cannulated titanium screw, with presumed superior endosteal purchase, to a similar 4.5 mm screw. Acute fifth metatarsal fractures were simulated in cadavers, stabilized with intramedullary screws, and loaded to failure in three-point bending. The initial failure loads for the metatarsals fixed with 4.5 mm and 5.5 mm screws were not significantly different (332.4 N vs. 335.2 N, respectively), nor were the ultimate failure loads (849.8 N vs. 702.2 N, respectively). Based upon our results, maximizing screw diameter does not appear to be critical for fixation rigidity and may increase the risk of intraoperative or postoperative fracture.

Telemetry system for monitoring anterior cruciate ligament graft forces in vivo.

Quantifying changes in the tension of an anterior cruciate ligament (ACL) graft in vivo during rehabilitative exercises is useful for developing the optimum rehabilitation for patients who have had reconstructive surgery. The purpose of the work reported is to design, build and test a telemetry system that can measure the in vivo ACL graft tension post-operatively. A commercially available fixation device is modified to sense the graft tension, house electronic components, transmit an output signal and pass the power generating signal. A transcutaneous inductive link is used to power the implanted telemetry electronics. The current difference technique is used to measure changes in two resistance strain gauges that monitor shear strain developed on the femoral fixation device by the ACL graft. This current regulates a frequency-modulated output signal that is transmitted using a new technique. Harnessing the ionic and volume conduction properties of the body fluids, the new technique involves injecting current subcutaneously into the tissue and then sensing the potential developed on the skin by surface electrodes. The waveform shape, amount of charge injected, charge density and current density are regulated to avoid tissue damage, pain and unwanted muscular stimulation. A signal conditioning board detects and converts the output to an analogue voltage for collection by a computer data-acquisition system. A performance evaluation demonstrates that the telemetry system either meets or exceeds all of the criteria necessary for the application.

A new technique for transmission of signals from implantable transducers.

To reduce space requirements for implant electronics in in vivo telemetry applications, the purpose of this project was to develop and test a new data transmission method that utilizes the ionic properties of bodily fluids as the transmission medium. Motivated by an interest in using the new method to transmit information from a sensor which measures tension in anterior cruciate ligament (ACL) grafts, a sine wave was injected into a cadaver leg using platinum electrodes implanted into the lateral femoral epicondyle. The signal was detected by electromyogram (EMG) surface electrodes. The effect of transmission frequency, the current injected, interelectrode separation, distance of the electrodes from the joint line, and the surface of electrode placement on the signal attenuation was studied. The logarithmic relation between attenuation and frequency was constant from 2 kHz until 10 kHz. For frequencies above 10 kHz, the attenuation increased linearly at the rate of 1 dB/octave. Attenuation was inversely sensitive to both current and interelectrode separation with larger separations and currents giving less attenuation. Attenuation was significantly less for the lateral thigh surface than for the anterior surface and increased with increasing distance from the joint line for both surfaces. For the application of interest here, suitable values of transmission variables to avoid the possible negative consequences of injecting current into living tissue are a current of 3 mA injected at a frequency of 37 kHz. The values of reception variables for minimum attenuation are wide interelectrode separation (5 cm) with the electrodes placed 5 cm proximal of the joint line on the lateral surface of the thigh. With the exception of the surface which is application dependent, these values of the reception variables should also be appropriate for other applications.