William A. Pierce

Effect of Recombinant Human Bone Morphogenetic Protein‐2 on Fracture Healing in a Goat Tibial Fracture Model

Bone morphogenetic proteins (BMPs) are considered to have important regulatory roles in skeletal embryogenesis and bone healing. Recombinant human BMPs (rhBMPs) have been shown to heal critical size defects and promote spinal fusion. We studied the effects of rhBMP‐2 in an absorbable collagen sponge (ACS) on bone healing in a large animal tibial fracture model. Bilateral closed tibial fractures were created in 16 skeletally mature goats and reduced and stabilized using external fixation. In each animal, one tibia received the study device (0.86 mg of rhBMP‐2/ACS or buffer/ACS), and the contralateral fracture served as control. The device was implanted as a folded onlay or wrapped circumferentially around the fracture. Six weeks following fracture, the animals were sacrificed and the tibiae harvested for torsional testing and histomorphologic evaluation. Radiographs indicated increased callus at 3 weeks in the rhBMP‐2/ACS treated tibiae. At 6 weeks, the rhBMP‐2/ACS wrapped fractures had superior radiographic healing scores compared with buffer groups and controls. The rhBMP‐2/ACS produced a significant increase in torsional toughness (p = 0.02), and trends of increased torsional strength and stiffness (p = 0.09) compared with fracture controls. The device placed in a wrapped fashion around the fracture produced significantly tougher callus (p = 0.02) compared with the onlay application. Total callus new bone volume was significantly increased (p = 0.02) in the rhBMP‐2/ACS fractures compared with buffer groups and controls regardless of the method of device application. The rhBMP‐2/ACS did not alter the timing of onset of periosteal/endosteal callus formation compared with controls. Neither the mineral apposition rates nor bone formation rates were affected by rhBMP‐2/ACS treatment. The increased callus volume associated with rhBMP‐2 treatment produced only moderate increases in strength and stiffness.

Recombinant human bone morphogenetic protein-2 enhances anterior spinal fusion in a thoracoscopically instrumented animal model.

BACKGROUND Thoracoscopically assisted anterior spinal arthrodesis and instrumentation is being used more widely to treat idiopathic scoliosis. However, harvesting autologous bone increases operative time and morbidity. The purpose of this study was to compare autologous iliac crest and rib graft with recombinant human bone morphogenetic protein-2 (rhBMP-2) in thoracoscopically assisted anterior spinal arthrodesis and instrumentation in an animal model. METHODS Twenty-two pigs underwent thoracoscopically assisted anterior spinal arthrodesis. Each animal had five contiguous thoracic discectomies followed by anterior instrumentation. The animals were randomly assigned to five treatment groups. Group I consisted of control animals that received no graft material; group II, animals treated with autologous rib graft; group III, animals treated with autologous iliac crest graft; group IV, animals treated with an rhBMP-2-composite sponge (collagen-hydroxyapatite-tricalcium phosphate carrier); and group V, animals treated with a composite sponge carrier alone. The animals were killed four months after the procedure, and the spines were harvested. The fusion mass was assessed with use of axial and sagittal computed tomography scans. The spines were tested biomechanically with incremental loads applied in the frontal and axial planes to achieve bending moments of up to 6.0 N-m. Angular motion at each segment was recorded with use of a three-dimensional motion analysis system. Histomorphometric analysis of each undecalcified disc segment was also performed. RESULTS The fusion grades, according to computed tomography analysis with use of a 4-point grading system in which scores of 3 and 4 indicated a solid fusion, were 0.6 point for group I, 2.1 points for group II, 2.3 points for group III, 3.8 points for group IV, and 0.4 point for group V. Group IV (the rhBMP-2-treated animals) had a higher grade than all of the other groups. Group II (rib graft) and group III (iliac crest) had similar grades, and both were greater than group I (the untreated controls) and group V (composite sponge alone) (p < 0.05). In axial rotation, lateral bending, and flexion-extension, the spines in group IV were stiffer than those in the four other groups (p < 0.05); the spines in groups II and III were similar, and the spines in both of those groups were stiffer than those in groups I and V (the control groups). Histologic analysis demonstrated that the total new-bone area, expressed as a percentage of the total disc space area, was 23.2% in group I, 37.1% in group II, 37.2% in group III, 48.5% in group IV, and 5.9% in group V. Group IV had significantly greater bone formation than all of the other groups (p < 0.001). The animals treated with rib graft (group II) and iliac crest (group III) had a similar amount of bone formation, and it was greater than that in both control groups (p < 0.001). CONCLUSIONS The rhBMP-2 significantly increased the prevalence and quality of the spinal fusion after thoracoscopically assisted anterior arthrodesis and instrumentation in an animal model compared with that in the other treatment groups and in the controls.

Impact of Tunnels and Tenodesis Screws on Clavicle Fracture: A Biomechanical Study of Varying Coracoclavicular Ligament Reconstruction Techniques

PURPOSE The purpose of this study was to compare the load to fracture of distal clavicles with no tunnels, one tunnel, or 2 tunnels and to evaluate the effect of inserting tenodesis screws in the tunnels on load to fracture of the distal clavicle. METHODS Fifty right sawbone clavicles were obtained and divided into 5 groups (n = 10): group 1, normal clavicle; group 2, one tunnel, no tenodesis screw; group 3, 2 tunnels, no tenodesis screws; group 4, one tunnel with tenodesis screw; and group 5, 2 tunnels with 2 tenodesis screws. Tunnels were created using a 5-mm-diameter reamer, and 5.5 × 10 mm polyethyl ethyl ketone tenodesis screws were used. A 4-point bending load was applied to the distal clavicles. Load to failure was noted for each specimen. RESULTS Load to failure in clavicles without tunnels was significantly higher (1,157.18 ± 147.10 N) than in all other groups (P < .0005). No statistical differences were noted between groups 2, 3, 4, and 5. Load to failure was not statistically different in clavicles with one versus 2 tunnels. In addition, the use of tenodesis screws in the tunnels did not affect the load required to fracture. CONCLUSIONS The use of tunnels in the clavicle for coracoclavicular (CC) ligament reconstruction significantly reduces the load required to fracture the distal clavicle. The addition of tenodesis screws does not appear to significantly increase the strength of the clavicle in this construct. CLINICAL RELEVANCE CC ligament reconstruction techniques commonly use tunnels in the distal clavicle, which may render the clavicle more susceptible to fracture. This study helps quantify the effect of these tunnels on the strength of the distal clavicle.

The effect of hemorrhagic shock in a caprine tibial fracture model

Objectives The purpose of this study was to assess effects of hemorrhagic shock on fracture healing in a large animal closed fracture model. Design Prospective randomized trial. Setting University Medical Center. Study Subjects Eight skeletally mature neutered male goats. Intervention Standardized bilateral closed midshaft tibia fractures were created in all the goats. The goats were randomized to a hemorrhage, shock and resuscitation group (shock group), or a control group. Hemorrhagic shock was induced in the four goats in the shock group. The shock state was maintained for thirty minutes. The remaining four goats were used as a control group. All fractures were stabilized with a standardized external fixator. Outcome Measures Swan-Ganz catheters were used to record cardiac output (CO). Arterial blood was sampled to determine base deficit values for the goats after hemorrhage. Radiographs were obtained weekly. After four weeks the tibias were harvested and nondestructively tested in torsion. Immediately after mechanical testing, the tibias were processed for histologic analysis. Standard histomorphologic indices, including total bone volume (TV/BV%), osteoblast surfaces (Ob/BS%), and osteoid surface (OS/BS%), were measured. Results One goat in the shock group became agitated upon emergence from anesthesia and dislodged two of his external fixator pins. This animal was killed and was not included in the analysis of results. One goat that would have been entered into the control group was then switched to the shock group, leaving four goats in the shock group and three in the control group. One goat in the shock group developed a nonunion of his left tibia fracture. This nonunion occurred because of loosening of pin fixation in the distal tibia. The nonunited bone was not included in the analysis of results. The animals right tibia healed uneventfully. Hemorrhage uniformly resulted in shock. In the shock group goats, average CO on induction of anesthesia was 3.7 l/min. Average CO dropped to 0.7 after hemorrhage and rose to 6.6 after fluid resuscitation. The average base deficit for the shock group animals was −9.9. The control group animals had minor drops in average CO, from 4.5 on induction of anesthesia to 4.3 on emergence from anesthesia. Radiographic analysis showed no apparent differences in healing between groups when comparing callus area and density. With the exception of the nonunion, all tibiae were considered to be healing normally radiographically. Biomechanical testing showed no statistical difference between the shock and control groups in maximum torque (p = 0.95), stiffness (p = 0.64), and energy absorbed at failure (p = 0.91). Histomorphologic results indicated there were no differences between groups. Shock did not appear to influence bone formation rate or callus remodeling compared with controls (p = 0.6). No evidence of osteocyte necrosis was observed. Conclusions In this study no significant difference was found between the shock and control groups in any of the parameters measured. Transient hemorrhagic shock does not appear to adversely affect closed tibia fracture healing in a goat model.

New rod-plate anterior instrumentation for thoracolumbar/lumbar scoliosis: Biomechanical evaluation compared with dual-rod and single-rod with structural interbody support

Study Design. A new rod-plate anterior implant was designed to provide plate fixation at the cephalad and caudal-end segments of a 5-level anterior spine construct. Biomechanical testing was performed on calf spines instrumented with 5-segment anterior scoliosis constructs. Objectives. To analyze the initial and post-fatigue biomechanical performance of the new implant, and compare it to an anterior dual-rod construct and a single-rod construct with interbody cages. Summary of Background Data. Using single-rod anterior instrumentation for thoracolumbar and lumbar scoliosis, an unacceptable incidence of loss of correction, segmental kyphosis, and pseudarthrosis has been reported. Inadequate construct stiffness due to early postoperative bone-screw interface failure, especially at cephalad and caudal-end vertebrae, has been implicated as the cause of these complications. Methods. Thirty calf spines were instrumented over 5 segments with: (1) single-rod augmented with rod-plate implants, (2) dual-rod construct, and (3) single-rod with titanium mesh cages. Stiffness in flexion-extension and lateral bending modes was determined initially and post-cyclical loading by measuring segmental range of motion (ROM). Post-fatigue screw pullout tests were also performed. Results. In lateral bending, the caudal-end segmental ROM for rod-plate construct was 54% less than single-rod with cages construct (P < 0.05), with no difference between rod-plate and dual-rod constructs. In flexion-extension, the rod-plate construct showed 45% to 91% (initial test) and 84% to 90% (post-fatigue) less ROM than the single-rod with cages construct (P < 0.001). Again, there was no difference between rod-plate and dual-rod constructs at the cephalad and caudal-end segments. Post-fatigue screw pullout strengths of the rod-plate construct were significantly greater than those of the dual-rod and single-rod with cages constructs (P < 0.05). Conclusions. The rod-plate construct was significantly stiffer and provided greater stability of bone-screw interfacethan the single-rod with cages construct. It achieved similar stiffness and improved bone-screw interface stability compared to dual-rod construct.

Biomechanical Analysis of Retrograde Flexible Intramedullary Nail Constructs in a Simulated Pediatric Femur Fracture Model

Background: Various flexible intramedullary nail (FIMN) constructs for pediatric femur fractures are described; however, no biomechanical study has compared stability of medial-lateral entry versus all-lateral entry retrograde nailing. Our purpose is to compare the rotational and bending stiffness of 2 different FIMN constructs and 2 different materials in a simulated pediatric femur fracture model. Methods: Eighty adolescent-sized composite femurs were used to simulate transverse (40 femurs) and oblique (40 femurs) mid-diaphyseal fractures. Retrograde FIMN of the femurs was performed using either 3.5 mm titanium (Ti) or 3.5 mm stainless-steel (SS) flexible nails in 2 configurations: 2 “C”-shaped nails (CC) placed through medial and lateral entry sites or 1 “C”-shaped nail and 1 “S”-shaped nail (CS) placed through a single lateral entry site. Models were first tested in 10 cycles of axial rotation to ±1 N m of torque at a rate of 0.5 degrees/s under 36 kg of compression. Axial compression was performed and bending stiffness defined as the force required to achieve 10 degrees varus at the fracture site. Results: No differences were noted in rotational stiffness comparing Ti and SS nails regardless of nail configuration or fracture pattern. Comparable rotational stability was found for CC and CS configurations with SS implants for both fracture patterns. The CS construct (0.60 N m/degree) was stiffer in rotation than the CC construct (0.41 N m/degree) with Ti implants in the transverse fracture model (P<0.005). SS nails provided greater bending stiffness than Ti nails in both oblique and transverse fracture patterns, regardless of nail construct. The all-lateral entry (CS) construct demonstrated statistically significant greater bending stiffness regardless of implant material or fracture pattern (P<0.03). Conclusions: An all-lateral entry (CS) FIMN construct demonstrated greater bending stiffness in both fracture patterns and materials. Ti and SS implants have comparable rotational stiffness in all fracture patterns and materials; however, SS nails were superior at resisting bending forces in both fracture patterns. CS nail configuration and SS implants demonstrated superior bending stiffness and rotational stiffness when compared with the more commonly used CC construct and Ti implants. Level of Evidence: NA (biomechanical study).

Detecting a disruption of blood flow to the femoral head after ischemic injury using 4 different techniques: A preliminary study

Background: Disruption of blood flow to the femoral head can have a detrimental effect on the clinical outcome after a closed or open reduction for the treatment of developmental dysplasia of the hip and after a treatment of slipped capital femoral epiphysis. Availability of a clinically reliable and easy-to-use technique to monitor the blood flow before, during, and after a therapeutic intervention may allow early detection and more effective management of this complication. An experimental investigation was performed to evaluate 4 different sensors/techniques for their ability to detect an acute disruption of blood flow to the immature femoral head. Methods: Under general anesthesia, the femoral heads of 10 immature pigs were exposed and total head ischemia was induced by ligating the femoral neck and transecting the ligamentum teres. Blood flow was assessed before and after the induction of ischemia using 1 of 4 techniques. The following sensors/techniques were evaluated: fiber optic pressure (FOP), piezoelectric pressure, partial pressure of oxygen, and laser Doppler flowmetry (LDF). The time taken to observe a 50% reduction of the preischemia level was determined and the sensor outputs were monitored until each reached a steady level. Results: All techniques demonstrated a reduction in their respective measurements after a disruption of blood flow to the femoral head. However, the response time differed, even between the 2 pressure sensors (FOP and piezoelectric pressure at 3 and 15 min, respectively). The fastest response time for a 50% reduction was observed with the LDF (2 min) and the FOP (3 min) sensors. The partial pressure of oxygen was the slowest to change, taking over 30 minutes. Technique-dependent advantages and disadvantages were seen. The FOP sensor was fragile and susceptible to the positioning of the sensor tip. The LDF sensor was susceptible to motion artifact. Conclusions: The LDF and the FOP sensors demonstrated a rapid decline in their respective measurements after the induction of ischemia. Clinical Relevance: These techniques may prove to be useful in the assessment of an acute disruption of the femoral head blood flow.

Novel dual-rod screw for thoracoscopic anterior instrumentation: biomechanical evaluation compared with single-rod and double-screw/double-rod anterior constructs.

Study Design. A novel dual-rod screw was designed to provide a second-rod augmentation at the critical apical/middle segments of the single-rod thoracoscopic anterior construct. Biomechanical testing was performed on pig thoracic spines instrumented with 7-segment anterior scoliosis constructs. Objectives. To analyze the biomechanical performance of the new implant, and compare it to a single-rod and double-rod anterior constructs. Summary of Background Data. Using single-rod thoracoscopic anterior instrumentation for thoracic scoliosis, the complications of rod breakage at apex, high rate of nonunion, and resultant loss of coronal and sagittal correction has been reported. Inadequate construct stiffness because of a smaller diameter single rod has been implicated as the cause of these complications. Methods. Twelve pig thoracic spines were instrumented over 7 segments with: (1) single-rod construct, (2) short second-rod augmentation at the apex of the single-rod construct, (3) long second-rod augmentation at middle segments of the single-rod construct, and (4) double-screw/double-rod anterior construct. The spines were tested in flexion-extension, left-right lateral bending, and torsion, using pure bending moments. Strain gauges attached to the primary single rod at the cephalad, middle, and caudal portions were used and the maximum tensile stress was recorded. Results. In the single-rod construct, the middle portion stress was 39% to 51% greater than the stress in the cephalad and caudal portions in flexion-extension (P < 0.05), and the cephalad portion stress was 39% to 65% greater than the stress in the middle and caudal portions in right lateral bending and torsion (P < 0.05). When a second rod was added at the apical/middle portion, the middle portion stress decreased from 50% to 72% in flexion-extension and right lateral bending (P < 0.05). In addition, the second rod decreased the primary single-rod stress at the cephalad portion by 48% (left torsion) and the caudal portion by 50% (flexion). Double-screw/double-rod construct significantly increases the construct stiffness in comparison with the single-rod construct. However, it did not add any construct stiffness at the critical apical segments when compared to the constructs in which the second rod augmented the single-rod constructs. Conclusion. A novel dual-rod screw was designed to combine the standard single-rod construct with the addition of a second rod at the critical apical/middle segments and increase construct stiffness and stability. This implant may therefore prevent pseudarthrosis and rod breakage by enhancing construct stiffness.