Safa T. Herfat

Applying Simulated In Vivo Motions to Measure Human Knee and ACL Kinetics

Patients frequently experience anterior cruciate ligament (ACL) injuries but current ACL reconstruction strategies do not restore the native biomechanics of the knee, which can contribute to the early onset of osteoarthritis in the long term. To design more effective treatments, investigators must first understand normal in vivo knee function for multiple activities of daily living (ADLs). While the 3D kinematics of the human knee have been measured for various ADLs, the 3D kinetics cannot be directly measured in vivo. Alternatively, the 3D kinetics of the knee and its structures can be measured in an animal model by simulating and applying subject-specific in vivo joint motions to a joint using robotics. However, a suitable biomechanical surrogate should first be established. This study was designed to apply a simulated human in vivo motion to human knees to measure the kinetics of the human knee and ACL. In pursuit of establishing a viable biomechanical surrogate, a simulated in vivo ovine motion was also applied to human knees to compare the loads produced by the human and ovine motions. The motions from the two species produced similar kinetics in the human knee and ACL. The only significant difference was the intact knee compression force produced by the two input motions.

Effect of Perturbing a Simulated Motion on Knee and Anterior Cruciate Ligament Kinetics

Current surgical treatments for common knee injuries do not restore the normal biomechanics. Among other factors, the abnormal biomechanics increases the susceptibility to the early onset of osteoarthritis. In pursuit of improving long term outcome, investigators must understand normal knee kinematics and corresponding joint and anterior cruciate ligament (ACL) kinetics during the activities of daily living. Our long term research goal is to measure in vivo joint motions for the ovine stifle model and later simulate these motions with a 6 degree of freedom (DOF) robot to measure the corresponding 3D kinetics of the knee and ACL-only joint. Unfortunately, the motion measurement and motion simulation technologies used for our project have associated errors. The objective of this study was to determine how motion measurement and motion recreation error affect knee and ACL-only joint kinetics by perturbing a simulated in vivo motion in each DOF and measuring the corresponding intact knee and ACL-only joint forces and moments. The normal starting position for the motion was perturbed in each degree of freedom by four levels (-0.50, -0.25, 0.25, and 0.50 mm or degrees). Only translational perturbations significantly affected the intact knee and ACL-only joint kinetics. The compression-distraction perturbation had the largest effect on intact knee forces and the anterior-posterior perturbation had the largest effect on the ACL forces. Small translational perturbations can significantly alter intact knee and ACL-only joint forces. Thus, translational motion measurement errors must be reduced to provide a more accurate representation of the intact knee and ACL kinetics. To account for the remaining motion measurement and recreation errors, an envelope of forces and moments should be reported. These force and moment ranges will provide valuable functional tissue engineering parameters (FTEPs) that can be used to design more effective ACL treatments.

Integrity of Damage Control Posterior Spinal Fusion Constructs for Patients With Polytrauma: A Biomechanical Investigation.

Study Design. Biomechanical. Objective. Evaluate spinal stability achieved with different levels of posterior percutaneous fixation (postPerc) for thoracolumbar fractures in cadavers subjected to ICU activities. Summary of Background Data. “Spine damage control” involves postPerc performed within 24 hours of injury and staged, elective, definitive stabilization. Amount of instrumentation needed to initially achieve adequate spinal stability, minimize morbidity, and accommodate ICU care needs between stages are not defined. Methods. In full-unembalmed cadavers motion-tracking sensors were placed at T11 and L1. A T12 corpectomy with PLC injury was stabilized with 1, 2, and 3 levels of PostPerc above/below the injury. Motions between T11 and L1 were measured during Log-Roll and Sit-Up on an ICU bed. After in situ testing, anatomic spinal motion ranges were determined under pure moment loads. Results. 5 cadavers were evaluated. For Log-Roll, 2 and 3 levels above/below restored stability to intact, whereas 1 level above/below did not for axial rotation. For translation, all instrumentation restored stability to intact. During Sit-Up, a linear increase in flexion was observed. At 45° Sit-Up, 2 and 3 levels above/below were similar to intact for flexion; 1 level above/below had significantly more flexion. All instrumentations restored translation to intact for Sit-Up; significantly more axial collapse occurred for instrumentation compared with intact. During ex situ testing, 2 and 3 levels above/below were similar; 1 level above/below had significantly greater laxity in flexion, extension, and axial rotation. Conclusion. Posterior instrumentation 2 or 3 levels above/below a severe thoracolumbar fracture model can restore spinal stability back to its intact condition. 2 levels of fixation above/below this “worst-case scenario” is minimum fixation sufficient to provide absolute spinal stability in the ICU setting as a “Damage Control” technique in patients with polytrauma. In less severe injury models, 1 level of fixation above/below may provide adequate spinal stability; although this should be confirmed in future investigations. Level of Evidence: N/A

Fatigue Failure in Extra-Articular Proximal Tibia Fractures: Locking Intramedullary Nail Versus Double Locking Plates-A Biomechanical Study.

Objectives: The goal of this study is to compare the fatigue strength of a locking intramedullary nail (LN) construct with a double locking plate (DLP) construct in comminuted proximal extra-articular tibia fractures. Methods: Eight pairs of fresh frozen cadaveric tibias with low bone mineral density [age: 80 ± 7 (SD) years, T-score: −2.3 ± 1.2] were used. One tibia from each pair was fixed with LN, whereas the contralateral side was fixed with DLP for complex extra-articular multifragmentary metaphyseal fractures (simulating OTA 41-A3.3). Specimens were cyclically loaded under compression simulating single-leg stance by staircase method out to 260,000 cycles. Every 2500 cycles, localized gap displacements were measured with a 3D motion tracking system, and x-ray images of the proximal tibia were acquired. To allow for mechanical settling, initial metrics were calculated at 2500 cycles. The 2 groups were compared regarding initial construct stiffness, initial medial and lateral gap displacements, stiffness at 30,000 cycles, medial and lateral gap displacements at 30,000 cycles, failure load, number of cycles to failure, and failure mode. Failure metrics were reported for initial and catastrophic failures. Results: DLP constructs exhibited higher initial stiffness and stiffness at 30,000 cycles compared with LN constructs (P < 0.03). There were no significant differences between groups for loads at failure or cycles to failure. Conclusions: For the fixation of extra-articular proximal tibia fractures, a LN provides a similar fatigue performance to double locked plates. The locked nail could be safely used for fixation of proximal tibia fractures with the advantage of limited extramedullary soft tissue damage.

Biomechanical comparison of long, short, and extended-short nail construct for femoral intertrochanteric fractures

OBJECTIVES Short and long cephalomedullary (CM) nails are commonly used construct for fixation of intertrochanteric (IT) fractures. Each of these constructs has its advantages and its shortcomings. The extended-short (ES) CM nail offers a hybrid between long and short nail design that aims to combine their respective benefits. The goals of this study were to (1) biomechanically evaluate and compare construct stiffness for the long, short and ES constructs in the fixation of IT fractures, and to (2) investigate the nature of periprosthetic fractures of constructs implanted with these various designs. METHODS Eighteen synthetic femora were used to evaluate three types of fracture fixation constructs. Axial compression, bending, and torsional stiffness were reported for both stable and comminuted IT fracture models. All comminuted fracture constructs were loaded to failure in axial compression to measure failure loads and evaluate periprosthetic fracture patterns. RESULTS Stiffness were similar among constructs with few exceptions. Axial stiffness was significantly higher for the short nail compared to the long nail for the comminuted model (p= 0.020). ES nail constructs exhibited a significantly higher failure load than short nail constructs (p = 0.039). Periprosthetic fractures occurred around the distal interlocking screw in all constructs. CONCLUSIONS Nail length and position of interlocking screw did not alter the biomechanical properties of the fixation construct in the presented IT fracture model. Periprosthetic fractures generated in this study had similar patterns to those seen clinically. This study also suggests that if a periprosthetic fracture is to occur, there is an increased probability of it happening around the site of the interlocking screw, regardless of nail design.

Effect of Surgery to Implant Motion and Force Sensors on Vertical Ground Reaction Forces in the Ovine Model

Activities of daily living (ADLs) generate complex, multidirectional forces in the anterior cruciate ligament (ACL). While calibration problems preclude direct measurement in patients, ACL forces can conceivably be measured in animals after technical challenges are overcome. For example, motion and force sensors can be implanted in the animal but investigators must determine the extent to which these sensors and surgery affect normal gait. Our objectives in this study were to determine (1) if surgically implanting knee motion sensors and an ACL force sensor significantly alter normal ovine gait and (2) how increasing gait speed and grade on a treadmill affect ovine gait before and after surgery. Ten skeletally mature, female sheep were used to test four hypotheses: (1) surgical implantation of sensors would significantly decrease average and peak vertical ground reaction forces (VGRFs) in the operated limb, (2) surgical implantation would significantly decrease single limb stance duration for the operated limb, (3) increasing treadmill speed would increase VGRFs pre- and post operatively, and (4) increasing treadmill grade would increase the hind limb VGRFs pre- and post operatively. An instrumented treadmill with two force plates was used to record fore and hind limb VGRFs during four combinations of two speeds (1.0 m/s and 1.3 m/s) and two grades (0 deg and 6 deg). Sensor implantation decreased average and peak VGRFs less than 10% and 20%, respectively, across all combinations of speed and grade. Sensor implantation significantly decreased the single limb stance duration in the operated hind limb during inclined walking at 1.3 m/s but had no effect on single limb stance duration in the operated limb during other activities. Increasing treadmill speed increased hind limb peak (but not average) VGRFs before surgery and peak VGRF only in the unoperated hind limb during level walking after surgery. Increasing treadmill grade (at 1 m/s) significantly increased hind limb average and peak VGRFs before surgery but increasing treadmill grade post op did not significantly affect any response measure. Since VGRF values exceeded 80% of presurgery levels, we conclude that animal gait post op is near normal. Thus, we can assume normal gait when conducting experiments following sensor implantation. Ultimately, we seek to measure ACL forces for ADLs to provide design criteria and evaluation benchmarks for traditional and tissue engineered ACL repairs and reconstructions.

Biomechanical Assessment of the Dorsal Spanning Bridge Plate in Distal Radius Fracture Fixation: Implications for Immediate Weight-Bearing:

Background: The goal of this study was to compare the biomechanical stability of a 2.4-mm dorsal spanning bridge plate with a volar locking plate (VLP) in a distal radius fracture model, during simulated crutch weight-bearing. Methods: Five paired cadaveric forearms were tested. A 1-cm dorsal wedge osteotomy was created to simulate an unstable distal radius fracture with dorsal comminution. Fractures were fixed with a VLP or a dorsal bridge plate (DBP). Specimens were mounted to a crutch handle, and optical motion-tracking sensors were attached to the proximal and distal segments. Specimens were loaded in compression at 1 mm/s on a servohydraulic test frame until failure, defined as 2 mm of gap site displacement. Results: The VLP construct was significantly more stable to axial load in a crutch weight-bearing model compared with the DBP plate (VLP: 493 N vs DBP: 332 N). Stiffness was higher in the VLP constructs, but this was not statistically significant (VLP: 51.4 N/mm vs DBP: 32.4 N/mm). With the crutch weight-bearing model, DBP failed consistently with wrist flexion and plate bending, whereas VLP failed with axial compression at the fracture site and dorsal collapse. Conclusions: Dorsal spanning bridge plating is effective as an internal spanning fixator in treating highly comminuted intra-articular distal radius fracture and prevents axial collapse at the radiocarpal joint. However, bridge plating may not offer advantages in early weight-bearing or transfer in polytrauma patients, with less axial stability in our crutch weight-bearing model compared with volar plating. A stiffer 3.5-mm DBP or use of a DBP construct without the central holes may be considered for distal radius fractures if the goal is early crutch weight-bearing through the injured extremity.

FGF and TGFβ signaling link form and function during jaw development and evolution

How does form arise during development and change during evolution? How does form relate to function, and what enables embryonic structures to presage their later use in adults? To address these questions, we leverage the distinct functional morphology of the jaw in duck, chick, and quail. In connection with their specialized mode of feeding, duck develop a secondary cartilage at the tendon insertion of their jaw adductor muscle on the mandible. An equivalent cartilage is absent in chick and quail. We hypothesize that species-specific jaw architecture and mechanical forces promote secondary cartilage in duck through the differential regulation of FGF and TGFβ signaling. First, we perform transplants between chick and duck embryos and demonstrate that the ability of neural crest mesenchyme (NCM) to direct the species-specific insertion of muscle and the formation of secondary cartilage depends upon the amount and spatial distribution of NCM-derived connective tissues. Second, we quantify motility and build finite element models of the jaw complex in duck and quail, which reveals a link between species-specific jaw architecture and the predicted mechanical force environment. Third, we investigate the extent to which mechanical load mediates FGF and TGFβ signaling in the duck jaw adductor insertion, and discover that both pathways are mechanoresponsive and required for secondary cartilage formation. Additionally, we find that FGF and TGFβ signaling can also induce secondary cartilage in the absence of mechanical force or in the adductor insertion of quail embryos. Thus, our results provide novel insights on molecular, cellular, and biomechanical mechanisms that couple musculoskeletal form and function during development and evolution.

New Opportunities for Fracture Healing Detection: Impedance Spectroscopy Measurements Correlate to Tissue Composition in Fractures.

Accurate evaluation of fracture healing is important for clinical decisions on when to begin weight‐bearing and when early intervention is necessary in cases of fracture nonunion. While the stages of healing involving hematoma, cartilage, trabecular bone, and cortical bone have been well characterized histologically, physicians typically track fracture healing by using subjective physical examinations and radiographic techniques that are only able to detect mineralized stages of bone healing. This exposes the need for a quantitative, reliable technique to monitor fracture healing, and particularly to track healing progression during the early stages of repair. The goal of this study was to validate the use of impedance spectroscopy to monitor fracture healing and perform comprehensive evaluation comparing measurements with histological evidence. Here, we show that impedance spectroscopy not only can distinguish between cadaver tissues involved throughout fracture repair, but also correlates to fracture callus composition over the middle stages of healing in wild‐type C57BL/6 mice. Specifically, impedance magnitude has a positive relationship with % trabecular bone and a negative relationship with % cartilage, and the opposite relationships are found when comparing phase angle to these same volume fractions of tissues. With this information, we can quantitatively evaluate how far a fracture has progressed through the healing stages. Our results demonstrate the feasibility of impedance spectroscopy for detection of fracture callus composition and reveals its potential as a method for early detection of bone healing and fracture nonunion.

Impedance spectroscopy to monitor fracture healing

An estimated 7.9 million fracture injuries occur each year in the United States, of which a substantial fraction result in delayed or non-union. Current methods of monitoring fracture healing include taking x-rays and making clinical observations. However, x-ray confirmation of bone healing typically lags behind biologic healing, and physician assessment of healing is fraught with subjectivity. No standardized methods exist to assess the extent of healing that has taken place in a fracture. Without such knowledge, interventions to aid healing and prevent fracture non-union are often delayed, leading to increased morbidity and suffering to patients. We are developing an objective measurement tool that utilizes electrical impedance spectroscopy to distinguish between the various types of tissue present during the different stages of fracture healing. Preliminary measurements of cadaveric tissues reveal adequate spread in impedance measurements and differences in frequency response among different tissue types. Electrodes implanted in a simulated fracture created in an ex vivo cadaver model yield promising results for our systems ability to differentiate between the stages of fracture healing.