Douglas C. Fredericks

Effects of pulsed electromagnetic fields on bone healing in a rabbit tibial osteotomy model.

OBJECTIVE The purpose of this study was to determine the effect of pulsed electromagnetic field (PEMF) exposure on healing tibial osteotomies in New Zealand White rabbits. DESIGN One-millimeter Gigli saw osteotomies were stabilized by external fixation. One day after surgery, rabbits were randomly assigned to receive either no exposure (sham control) or thirty minutes or sixty minutes per day of low-frequency, low-amplitude PEMF. Radiographs were obtained weekly throughout the study. Rabbits were euthanized at fourteen, twenty-one, or twenty-eight days, and tibiae underwent either destructive torsional testing or histologic analysis. To determine the baseline torsional strength and stiffness of rabbit tibiae, eleven normal intact tibiae were tested to failure. RESULTS Sixty-minute PEMF-treated osteotomies had significantly higher torsional strength than did sham controls at fourteen and twenty-one days postoperatively. Thirty-minute PEMF-treated osteotomies were significantly stronger than sham controls only after twenty-one days. Normal intact torsional strength was achieved by fourteen days in the sixty-minute PEMF group, by twenty-one days in the thirty-minute PEMF group, and by twenty-eight days in the sham controls. Maximum fracture callus area correlated with the time to reach normal torsional strength. CONCLUSION In this animal model, low-frequency, low-amplitude PEMF significantly accelerated callus formation and osteotomy healing in a dose-dependent manner.

Vertical shear injuries: is there a relationship between residual displacement and functional outcome?

BACKGROUND Residual vertical displacement is often cited as being related to poor outcome in patients with pelvic injuries. This study attempts to clarify the relationship between residual vertical displacement and functional outcome. METHODS From 1982 to 1989, over 500 patients with pelvic ring injuries were treated at two Level I trauma centers. Thirty-three patients with vertical shear (Tile C) fractures and residual displacement (2-52 mm) were evaluated. Outcomes were quantified by using SF-36 Short-Form Health Survey (SF-36) and the Iowa Pelvic Score (IPS). RESULTS There was no correlation between IPS or SF-36 scales and residual vertical displacement. The IPS correlated (p<0.05) with seven of eight SF-36 categories, excluding mental health. Patients reporting limp and leg length discrepancy also correlated with the IPS and select SF-36. CONCLUSION Pelvic injuries showed no correlation between functional outcome and residual vertical displacement suggesting other factors. The degree of residual vertical displacement does not affect functional outcome.

Instability Dependency of Osteoarthritis Development in a Rabbit Model of Graded Anterior Cruciate Ligament Transection

BACKGROUND Joint instability has long been empirically recognized as a leading risk factor for osteoarthritis. However, formal mechanistic linkage of instability to osteoarthritis development has not been established. This study aimed to support a clinically accepted, but heretofore scientifically unproven, concept that the severity and rapidity of osteoarthritis development in unstable joints is dependent on the degree of instability. In a survival rabbit knee model of graded joint instability, the relationship between the magnitude of instability and the intensity of cartilage degeneration was studied at the organ level in vivo. METHODS Sixty New Zealand White rabbits received either complete or partial (medial half) transection of the anterior cruciate ligament or sham surgery (control) on the left knee. At the time that the animals were killed at eight or sixteen weeks postoperatively (ten animals for each treatment and/or test-period combination), the experimental knees were subjected to sagittal plane stability measurement, followed by whole-joint cartilage histological evaluation with use of the Mankin score. RESULTS Sagittal plane instability created in the partial transection group was intermediate between those in the complete transection and sham surgery groups. The partial and complete transection groups exhibited cartilage degeneration on the medial femoral and/or medial tibial surfaces. The average histological score (and standard deviation) for the medial compartment in the partial transection group (2.9 ± 0.9) was again intermediate, significantly higher than for the sham surgery group (1.9 ± 0.8) and significantly lower than for the complete transection group (4.5 ± 2.3). The average histological scores for the medial compartment in the partial transection group correlated significantly with the magnitude of instability, with no threshold effect being evident. The significance level of alpha was set at 0.05 for all tests. CONCLUSIONS The severity of cartilage degeneration increased continuously with the degree of instability in this survival rabbit knee model of graded instability.

Effects of pulsed electromagnetic field stimulation on distraction osteogenesis in the rabbit tibial leg lengthening model.

The purpose of this study was to determine whether exposure to pulsed electromagnetic field (PEMF) would shorten the healing time of regenerate bone in a rabbit tibial distraction model. Beginning 1 day after surgery, mid-shaft tibial osteotomies, stabilized with external fixators, were distracted 0.25 mm twice daily for 21 days and received either no exposure (sham control) or 1 hour per day exposure to low-amplitude, low-frequency PEMF. Tibiae were tested for torsional strength after 9, 16, and 23 days post-distraction. PEMF-treated tibiae were significantly stronger than shams at all three time points. By 16 days post-distraction, the PEMF group had achieved biomechanical strength essentially equivalent to intact bone. Shams did not achieve normal biomechanical strength even after 23 days post-distraction. In this tibial distraction model, short daily PEMF exposures accelerated consolidation of regenerate bone. Clinical usefulness awaits testing.

Effects of direct current electrical stimulation on gene expression of osteopromotive factors in a posterolateral spinal fusion model.

Study Design. An in vivo model was used to determine levels of mRNA expression in response to direct current (DC) electrical stimulation in a rabbit posterolateral fusion model. Objectives. This study tested the possibility that DC stimulation at the surgery site would increase expression of genes related to bone formation relative to expression in autograft alone. Summary of Background Data. DC electrical stimulation as an adjunct treatment in spinal surgery has shown increased fusion rates when compared with autograft alone, yet the biology of such treatment is not fully understood. Methods. Thirty New Zealand White rabbits were entered into the study. A posterolateral, intertransverse process fusion was performed bilaterally at L4–L5, with autogenous bone graft. An implantable DC stimulator was placed across the decorticated transverse processes before placement of autograft. Animals were killed at 3, 7, 14, 21, and 28 days. mRNA levels of BMP-2, 4, 6, 7, VEGF, FGF-2, TGF-β, ALK-2, and ALK-3 were evaluated with real-time RT-PCR. Results. mRNA expression was significantly higher in the DC stimulated animals versus the control animals for several of the genes studied. In particular, levels of mRNA were elevated for BMP-2, BMP-6, and BMP-7. Conclusions. This study shows for the first time that DC stimulation results in a sustained increase of multiple osteogenic genes, suggesting that the biologic mechanism for the DC-induced increase in the rate and extent of bone formation observed clinically may be mediated by the up-regulation of these osteoinductive factors.

B2A Peptide on Ceramic Granules Enhance Posterolateral Spinal Fusion in Rabbits Compared With Autograft

Study Design. Six groups of 10 animals underwent single level, uninstrumented posterolateral lumbar fusions. Graft sites were implanted with autologous bone, autologous bone plus B2A coated granules with concentrations of 0-, 50-, 100-, or 300 &mgr;g/mL, or no graft material. Explanted motion segments were analyzed by Faxitron radiographs, computerized tomography (CT), manual palpation, and histology. Objective. The synthetic peptide B2A2-K-NS (B2A) was evaluated as a novel agent for augmenting spinal fusion in a posterolateral, noninstrumented rabbit lumbar spine fusion model. Summary of Background Data. There have been many efforts to increase the rate of posterolateral spinal fusion while, at the same time minimizing, use of autologous bone with its inherent harvest morbidity. Methods. B2A coated ceramic granules (0-, 50-, 100-, and 300 &mgr;g/mL) were mixed 1:1 with autogenous iliac crest bone and implanted. Autogenous bone alone was used as a positive control. Fusion was assessed at 6 weeks via radiographs and manual palpation. These results were confirmed with histology and CT. Results. Fusion results from palpation and radiographic evaluations were similar. CT and histology confirmed bridging bone across the transverse processes for fused spines. The highest fusion rates were observed in the 100 &mgr;g B2A/mL group—89% in comparison to 33% for uncoated granules (0 &mgr;g B2A/mL) and 63% for autograft alone. These differences were statistically significant. Conclusion. All investigated B2A concentrations demonstrated increased fusion rates. Fusion masses resulting from the implantation of 100 &mgr;g B2A/mL granules demonstrated new woven bone: fused to the transverse processes, within granule pores, bridging bone across the transverse processes, and bridging residual bone graft and granules. It was concluded that each investigated concentration of B2A coated granules in a 1:1 mixture with autograft increased fusion rates in comparison to controls in this rabbit model.

Biomechanical Analysis of Cervical Disc Replacement and Fusion Using Single Level, Two Level, and Hybrid Constructs

Study Design. A biomechanical study comparing arthroplasty with fusion using human cadaveric C2–T1 spines. Objective. To compare the kinematics of the cervical spine after arthroplasty and fusion using single level, 2 level and hybrid constructs. Summary of Background Data. Previous studies have shown that spinal levels adjacent to a fusion experience increased motion and higher stress which may lead to adjacent segment disc degeneration. Cervical arthroplasty achieves similar decompression but preserves the motion at the operated level, potentially decreasing the occurrence of adjacent segment disc degeneration. Methods. 11 specimens (C2–T1) were divided into 2 groups (BRYAN and PRESTIGE LP). The specimens were tested in the following order; intact, single level total disc replacement (TDR) at C5–C6, 2-level TDR at C5–C6–C7, fusion at C5–C6 and TDR at C6–C7 (Hybrid construct), and lastly a 2-level fusion. The intact specimens were tested up to a moment of 2.0 Nm. After each surgical intervention, the specimens were loaded until the primary motion (C2–T1) matched the motion of the respective intact state (hybrid control). Results. An arthroplasty preserved motion at the implanted level and maintained normal motion at the nonoperative levels. Arthrodesis resulted in a significant decrease in motion at the fused level and an increase in motion at the unfused levels. In the hybrid construct, the TDR adjacent to fusion preserved motion at the arthroplasty level, thereby reducing the demand on the other levels. Conclusion. Cervical disc arthroplasty with both the BRYAN and PRESTIGE LP discs not only preserved the motion at the operated level, but also maintained the normal motion at the adjacent levels. Under simulated physiologic loading, the motion patterns of the spine with the BRYAN or PRESTIGE LP disc were very similar and were closer than fusion to the intact motion pattern. An adjacent segment disc replacement is biomechanically favorable to a fusion in the presence of a pre-existing fusion. Level of Evidence: N/A

Intracranial Somatosensory Responses with Direct Spinal Cord Stimulation in Anesthetized Sheep

The efficacy of spinal cord stimulators is dependent on the ability of the device to functionally activate targeted structures within the spinal cord, while avoiding activation of near-by non-targeted structures. In theory, these objectives can best be achieved by delivering electrical stimuli directly to the surface of the spinal cord. The current experiments were performed to study the influence of different stimulating electrode positions on patterns of spinal cord electrophysiological activation. A custom-designed spinal cord neurostimulator was used to investigate the effects of lead position and stimulus amplitude on cortical electrophysiological responses to spinal cord stimulation. Brain recordings were obtained from subdural grids placed in four adult sheep. We systematically varied the position of the stimulating lead relative to the spinal cord and the voltage delivered by the device at each position, and then examined how these variables influenced cortical responses. A clear relationship was observed between voltage and electrode position, and the magnitude of high gamma-band oscillations. Direct stimulation of the dorsal column contralateral to the grid required the lowest voltage to evoke brain responses to spinal cord stimulation. Given the lower voltage thresholds associated with direct stimulation of the dorsal column, and its possible impact on the therapeutic window, this intradural modality may have particular clinical advantages over standard epidural techniques now in routine use.

Ovine Tests of a Novel Spinal Cord Neuromodulator and Dentate Ligament Fixation Method

ABSTRACT Background: To improve methods for the treatment of intractable pain, we are developing a novel intradural spinal cord stimulator that could be either attached to the dentate ligaments of the human spinal cord or fitted around the dorsal arc of the cord itself. Purpose: Our goal was to carry out the first in vivo tests of these attachment methods in an ovine model using custom-built devices and instrumentation. For eventual translational studies, we also explored methods of mimicking a human dentate ligament attachment technique in this large animal model. Methods: As a starting point, we investigated details of the gross and histological anatomy of the ovine denticulate ligaments, and compared them with their human counterpart. The gap between the dura and the spinal cord in the sheep is small; hence, the denticulate ligaments are not long enough to accommodate human-scaled attachment clips. Therefore, lateral strips of the spinal-canal dura were fashioned to serve this same device attachment function. Results: This form of dural anchoring was implemented surgically for fixation of a silicone membrane implant that had 12 electrodes, and somatosensory evoked potentials were obtained successfully when stimuli were applied to it. The dorsal arc clamping technique was also implemented. Conclusions: We demonstrated that the dural attachment method is an effective surrogate model for testing the human dentate ligament device fixation technique, and that this mode of fixation was preferable to dorsal arc attachment. The relevant surgical innovations, anatomical findings, and the preliminary electrophysiological data from a pial surface stimulator attached in this way are presented.

The effect of transdermal nicotine on fracture healing in a rabbit model.

Objective: Cigarette smoking inhibits fracture healing and places the patient at a higher risk of delayed union and nonunion. Nicotine has been implicated as the primary ingredient responsible for these effects. However, an analysis of current published investigations reveals conflicting data, with some evidence that nicotine alone does not significantly affect healing. We undertook an animal study of the effects of transdermal nicotine on fracture healing. Methods: Twenty-two adult male New Zealand white rabbits were randomly assigned to the nicotine group or the control group. A midshaft tibial osteotomy was performed on the left tibiae of all 22 rabbits. The nicotine rabbits were exposed using a 10.5-mg transdermal patch applied daily to the ear. Radiographs were obtained, and the area of fracture callus was assessed. Rabbits were euthanized at 21 days. Fractures were stressed to failure, and load/deformation curves were recorded. Results: The average area of callus formation was greater in the control group (Control: 0.158 cm2, Nicotine: 0.124 cm2), but the difference was not statistically significant (P = 0.30). There was a significant difference between the 2 groups for mean normalized torque to failure (Nicotine: 36% of nonfractured side, Control: 69% of nonfractured side, P = 0.028). The control group mean normalized stiffness was significantly greater than that for the nicotine rabbits (Control: 87%, Nicotine: 43%, P = 0.036). There were 3 nonunions in the nicotine group (27%) compared with none in the control group (P = 0.062). Conclusions: In a rabbit model of fracture healing, transdermal nicotine exposure resulted in decreased mechanical strength of healing fractures at 21 days and a higher rate of nonunion at 21 days compared with that of controls.