Determine the vertical ground reaction forces and knee mechanics with different gait inclinations in the sheep model.

Our current understanding of knee mechanics and anterior cruciate ligament (ACL) function is predominately based on data recorded during simulations of clinical examinations or the application of nonphysiologic loads and motions. These methodologies provide little information on knee and ACL mechanics during activities of daily living (ADLs). Additionally, researchers have not directly measured knee kinetics, knee contact pressures, and ACL forces, and it is unknown how these parameters change with different activities. This study quantified the effects of activity level on vertical ground reaction forces, knee kinematics, and joint and ligament forces during in vivo motions. Five female Suffolk sheep were walked twice weekly on a treadmill during level (0°), inclined (+6°), and declined (-6°) gait for 12 weeks. Electromagnetic (EM) trackers were surgically implanted onto the left distal femur and the left proximal tibia, and in vivo motions were recorded for all activities. Following sacrifice, the in vivo motions were applied to their respective knees using a serial robot with a multi-axis load cell. In vitro simulations were repeated to measure (a) total knee forces, (b) contact pressure maps, and (c) ACL-only forces. Declining the gait surface led to increased posterior translation during the swing phase and decreased flexion at hoof-strike, decreased medial contact pressure at push-off, decreased ACL force at hoof-strike and increased ACL force at push-off. This study established a system that can be used to examine knee mechanics and ACL forces during ADLs for different knee states to define design requirements for ACL reconstruction techniques.

The influence of internal and external tibial rotation offsets on knee joint and ligament biomechanics during simulated athletic tasks.

BACKGROUND: Following anterior cruciate ligament injury and subsequent reconstruction transverse plane tibiofemoral rotation becomes underconstrained and overconstrained, respectively. Conflicting reports exist on how rotations influence loading at the knee. This investigation aimed to determine the mechanical effects of internal and external tibial rotation offsets on knee kinematics and ligament strains during in vitro simulations of in vivo recorded kinematics. METHOD: A 6-degree-of-freedom robotic manipulator arm was used to articulate 11 cadaveric tibiofemoral joint specimens through simulations of four athletic tasks produced from in vivo recorded kinematics. These simulations were then repeated with 4° tibial rotation offsets applied to the baseline joint orientation. FINDINGS: Rotational offsets had a significant effect on peak posterior force for female motion simulations (P < 0.01), peak lateral force for most simulated tasks (P < 0.01), and peak anterior force, internal torque, and flexion torque for sidestep cutting tasks (P ≤ 0.01). Rotational offsets did not exhibit statistically significant effects on peak anterior cruciate ligament strain (P > 0.05) or medial collateral ligament strain (P > 0.05) for any task. INTERPRETATION: Transverse plane rotational offsets comparable to those observed in anterior cruciate ligament deficient and reconstructed patients alter knee kinetics without significantly altering anterior cruciate ligament strain. As knee degeneration is attributed to abnormal knee loading profiles, altered transverse plane kinematics may contribute to this. However, altered transverse plane rotations likely play a limited role in anterior cruciate ligament injury risk as physiologic offsets failed to significantly influence anterior cruciate ligament strain during athletic tasks.

Effects of Population Variability on Knee Loading During Simulated Human Gait.

Cadaveric simulation models allow researchers to study native tissues in situ. However, as tests are conducted using donor specimens with unmatched kinematics, techniques that impose population average motions are subject to deviation from true physiologic conditions. This study aimed to identify factors which explain the kinetic variability observed during robotic simulations of a single human gait motion using a sample of human cadaver knees. Twelve human cadaver limbs (58 ± 16 years) were subjected to tibiofemoral geometrical analysis and cyclical stiffness testing in each anatomical degree of freedom. A simulated gait motion was then applied to each specimen. Resulting kinetics, specimen geometries, and various representations of tissue stiffness were reduced to functional attributes using principal component analysis and fit to a generalized linear prediction model. The capacity of knee topography to generate force was the largest contributor to kinetic variation in compression. Overall joint size, femoral notch height, translational laxity, and ad/abduction stiffness significantly contributed to kinetic variation in medial/lateral and anterior/posterior forces and associated torques. Future studies will investigate customizing kinematic paths to better simulate native conditions and reduce sampling variation, improving biomechanical test methods and evaluation strategies for future orthopedic techniques.

Knee Abduction Affects Greater Magnitude of Change in ACL and MCL Strains Than Matched Internal Tibial Rotation In Vitro.

BACKGROUND: Anterior cruciate ligament (ACL) injures incur over USD 2 billion in annual medical costs and prevention has become a topic of interest in biomechanics. However, literature conflicts persist over how knee rotations contribute to ACL strain and ligament injury. To maximize the efficacy of ACL injury prevention, the effects of underlying mechanics need to be better understood. QUESTIONS/PURPOSES: We applied robotically controlled, in vivo-derived kinematic stimuli to the knee to assess ligament biomechanics in a cadaver model. We asked: (1) Does the application of abduction rotation increase ACL and medial collateral ligament (MCL) strain relative to the normal condition? (2) Does the application of internal tibial rotation impact ACL strain relative to the neutral condition? (3) Does combined abduction and internal tibial rotation increase ligament strain more than either individual contribution? METHODS: A six-degree-of-freedom robotic manipulator was used to position 17 cadaveric specimens free from knee pathology outside of low-grade osteoarthritis (age, 47 ± 8 years; 13 males, four females) into orientations that mimic initial contact recorded from in vivo male and female drop vertical jump and sidestep cutting activities. Four-degree rotational perturbations were applied in both directions from the neutral alignment position (creating an 8° range) for each frontal, transverse, and combined planes while ACL and MCL strains were continuously recorded with DVRT strain gauges implanted directly on each ligament. Analysis of variance models with least significant difference post hoc analysis were used to assess differences in ligament strain and joint loading between sex, ligament condition, or motion task and rotation type. RESULTS: For the female drop vertical jump simulation in the intact knee, isolated abduction and combined abduction/internal rotational stimuli produced the greatest change in strain from the neutral position as compared with all other stimuli within the ACL (1.5% ± 1.0%, p ≤ 0.035; 1.8% ± 1.3%, p ≤ 0.005) and MCL (1.8% ± 1.0%, p < 0.001; 1.6% ± 1.3%, p < 0.001) compared with all other applied stimuli. There were no differences in mean peak ACL strain between any rotational stimuli (largest mean difference = 2.0%; 95% confidence interval [CI], -0.9% to 5.0%; p = 0.070). These trends were consistent for all four simulated tasks. Peak ACL strain in the intact knee was larger than peak MCL strain for all applied rotational stimuli in the drop vertical jump simulations (smallest mean difference = 2.1%; 95% CI, -0.4% to 4.5%; p = 0.047). CONCLUSIONS: Kinematically constrained cadaveric knee models using peak strain as an outcome variable require greater than 4° rotational perturbations to elicit changes in intraarticular ligaments. CLINICAL RELEVANCE: Because combined rotations and isolated abduction produced greater change in strain relative to the neutral position for the ACL and MCL than any other rotational stimuli in this cadaver study, hypotheses for in vivo investigations aimed toward injury prevention that focuses on the reduction of frontal plane knee motion should be considered. Furthermore, reduced strain in the MCL versus the ACL may help explain why only 30% of ACL ruptures exhibit concomitant MCL injuries.

Robotic simulation of identical athletic-task kinematics on cadaveric limbs exhibits a lack of differences in knee mechanics between contralateral pairs.

Limb asymmetry is a known factor for increased ACL injury risk. These asymmetries are normally observed during in vivo testing. Prior studies have developed in vitro testing methodologies driven by in vivo kinematics to investigate knee mechanics relative to ACL injury. The objective of this study was to determine if mechanical side-to-side asymmetries persist in contralateral pairs during in vitro simulation testing. In vivo kinematics were recorded for male and female drop vertical jump and sidestep cutting tasks. The recorded kinematics were used to robotically simulate the motions on 7 contralateral pairs of cadaveric lower extremities specimens. ACL and MCL force, torque, and strains were recorded and analyzed for differences between contralateral pairs. There was a general lack of mechanical differences between limb sides. Adduction peak torque for the male sidestep cut movement was significantly different between limb sides (p=0.04). However, this is consistent with ACL injury mechanics in that movement in the frontal plane (abduction/adduction) increases injury risk and it is possible loading differences in this plane may have resulted from tolerances within the setup process. The findings of this study indicate that contralateral knee joints were representative of each other during biomechanical in vitro tests. In future cadaveric robotic simulations, contralateral limbs can be used interchangeably. In addition, direct comparisons of the structural behaviors of isolated conditions for contralateral knee joints can be performed.

The LG/J murine strain exhibits near-normal tendon biomechanical properties following a full-length central patellar tendon defect.

PURPOSE OF THE STUDY: Identifying biological success criteria is needed to improve therapies, and one strategy for identifying them is to analyze the RNA transcriptome for successful and unsuccessful models of tendon healing. We have characterized the MRL/MpJ murine strain and found improved mechanical outcomes following a central patellar tendon (PT) injury. In this study, we evaluate the healing of the LG/J murine strain, which comprises 75% of the MRL/MpJ background, to determine if the LG/J also exhibits improved biomechanical properties following injury and to determine differentially expressed transcription factors across the C57BL/6, MRL/MpJ and the LG/J strains during the early stages of healing. MATERIALS AND METHODS: A full-length, central PT defect was created in 16-20 week old MRL/MpJ, LG/J, and C57BL/6 murine strains. Mechanical properties were assessed at 2, 5, and 8 weeks post surgery. Transcriptomic expression was assessed at 3, 7, and 14 days following injury using a novel clustering software program to evaluate differential expression of transcription factors. RESULTS: Average LG/J structural properties improved to 96.7% and 97.2% of native LG/J PT stiffness and ultimate load by 8 weeks post surgery, respectively. We found the LG/J responded by increasing expression of transcription factors implicated in the inflammatory response and collagen fibril organization. CONCLUSIONS: The LG/J strain returns to normal structural properties by 8 weeks, with steadily increasing properties at each time point. Future work will characterize the cell populations responding to injury and investigate the role of the differentially expressed transcription factors during healing.

Posterior Tibial Slope Angle Correlates With Peak Sagittal and Frontal Plane Knee Joint Loading During Robotic Simulations of Athletic Tasks.

BACKGROUND: Tibial slope angle is a nonmodifiable risk factor for anterior cruciate ligament (ACL) injury. However, the mechanical role of varying tibial slopes during athletic tasks has yet to be clinically quantified. PURPOSE: To examine the influence of posterior tibial slope on knee joint loading during controlled, in vitro simulation of the knee joint articulations during athletic tasks. STUDY DESIGN: Descriptive laboratory study. METHODS: A 6 degree of freedom robotic manipulator positionally maneuvered cadaveric knee joints from 12 unique specimens with varying tibial slopes (range, -7.7° to 7.7°) through drop vertical jump and sidestep cutting tasks that were derived from 3-dimensional in vivo motion recordings. Internal knee joint torques and forces were recorded throughout simulation and were linearly correlated with tibial slope. RESULTS: The mean (±SD) posterior tibial slope angle was 2.2° ± 4.3° in the lateral compartment and 2.3° ± 3.3° in the medial compartment. For simulated drop vertical jumps, lateral compartment tibial slope angle expressed moderate, direct correlations with peak internally generated knee adduction (r = 0.60-0.65), flexion (r = 0.64-0.66), lateral (r = 0.57-0.69), and external rotation torques (r = 0.47-0.72) as well as inverse correlations with peak abduction (r = -0.42 to -0.61) and internal rotation torques (r = -0.39 to -0.79). Only frontal plane torques were correlated during sidestep cutting simulations. For simulated drop vertical jumps, medial compartment tibial slope angle expressed moderate, direct correlations with peak internally generated knee flexion torque (r = 0.64-0.69) and lateral knee force (r = 0.55-0.74) as well as inverse correlations with peak external torque (r = -0.34 to -0.67) and medial knee force (r = -0.58 to -0.59). These moderate correlations were also present during simulated sidestep cutting. CONCLUSION: The investigation supported the theory that increased posterior tibial slope would lead to greater magnitude knee joint moments, specifically, internally generated knee adduction and flexion torques. CLINICAL RELEVANCE: The knee torques that positively correlated with increased tibial slope angle in this investigation are associated with heightened risk of ACL injury. Therefore, the present data indicated that a higher posterior tibial slope is correlated to increased knee loads that are associated with heightened risk of ACL injury.

Sex-based differences in knee ligament biomechanics during robotically simulated athletic tasks.

ACL injury rates are greater in female athletes than their male counterparts. As female athletes are at increased risk, it is important to understand the underlying mechanics that contribute to this sex bias. The purpose of this investigation was to employ a robotic manipulator to simulate male and female kinematics from athletic tasks on cadaveric specimens and identify sex-based mechanical differences relative to the ACL loading. It was hypothesized that simulations of female motion would generate the higher loads and ligament strains associated with in vivo ACL injury risk than simulations of male motion. A 6-degree-of-freedom robotic manipulator articulated cadaveric lower extremity specimens from 12 donors through simulations of in vivo kinematics recorded from male and female athletic tasks. Simulation of female kinematics exhibited lower peak lateral joint force during the drop vertical jump and lower peak anterior and lateral joint force and external joint torque during the sidestep cut (P<0.05). Peak ACL strain during a drop vertical jump was 6.27% and 6.61% for the female and male kinematic simulations, respectively (P=0.86). Peak ACL strain during a sidestep cut was 4.33% and 7.57% for female and male kinematic simulations respectively (P=0.21). For the tasks simulated, the sex-based loading and strain differences identified were unlikely to have a significant bearing on the increased rate of ACL injures observed in female athletes. Additional perturbation may be necessary to invoke the mechanisms that lead to higher rates of ACL injury in female populations.

Impacts of Robotic Compliance and Bone Bending on Simulated in vivo Knee Kinematics.

Robotic testing offers researchers the opportunity to quantify native tissue loads for the structures of the knee joint during activities of daily living. These loads may then be translated into design requirements for future treatments and procedures to combat the early onset of knee degeneration following an injury. However, high knee loads during testing have the potential to deflect a robotic end effector and cause inaccuracies in the applied kinematics. Furthermore, bone bending could also induce kinematic change. This study aimed to quantify the effects of robotic compliance and bone bending on the accuracy of simulated in vivo kinematics in a KUKA KRC210 serial robotic system. Six (6) human cadaver knees were subjected to cyclic human gait motion while 6 DOF forces and torques were recorded at the joint. A Vicon T-Series camera system was used to independently record the applied kinematics. Periods of highest kinematic deviation occurred during instances of low joint loading, suggesting negligible levels of forced deflection for simulations of moderate levels of activity while results of this small study indicate that high physiologic loading poses low risk of deviation from target kinematics, further testing is necessary to confirm.

Effect of ACL graft material on anterior knee force during simulated in vivo ovine motion applied to the porcine knee: An in vitro examination of force during 2000 cycles.

This study determined how anterior cruciate ligament (ACL) reconstruction affected the magnitude and temporal patterns of anterior knee force and internal knee moment during 2000 cycles of simulated gait. Porcine knees were tested using a six degree-of-freedom robot, examining three porcine allograft materials compared with the native ACL. Reconstructions were performed using: (1) bone-patellar tendon-bone allograft (BPTB), (2) reconstructive porcine tissue matrix (RTM), or (3) an RTM-polymer hybrid construct (Hybrid). Forces and moments were measured over the entire gait cycle and contrasted at heel strike, mid stance, toe off, and peak flexion. The Hybrid construct performed the best, as magnitude and temporal changes in both anterior knee force and internal knee moment were not different from the native ACL knee. Conversely, the RTM knees showed greater loss in anterior knee force during 2000 cycles than the native ACL knee at heel strike and toe off, with an average force loss of 46%. BPTB knees performed the least favorably, with significant loss in anterior knee force at all key points and an average force loss of 61%. This is clinically relevant, as increases in post-operative knee laxity are believed to play a role in graft failure and early onset osteoarthritis.

Relative strain in the anterior cruciate ligament and medial collateral ligament during simulated jump landing and sidestep cutting tasks: implications for injury risk.

BACKGROUND: The medial collateral (MCL) and anterior cruciate ligaments (ACL) are, respectively, the primary and secondary ligamentous restraints against knee abduction, which is a component of the valgus collapse often associated with ACL rupture during athletic tasks. Despite this correlation in function, MCL ruptures occur concomitantly in only 20% to 40% of ACL injuries. HYPOTHESIS/PURPOSE: The purpose of this investigation was to determine how athletic tasks load the knee joint in a manner that could lead to ACL failure without concomitant MCL failure. It was hypothesized that (1) the ACL would provide greater overall contribution to intact knee forces than the MCL during simulated motion tasks and (2) the ACL would show greater relative peak strain compared with the MCL during simulated motion tasks. STUDY DESIGN: Controlled laboratory study. METHODS: A 6-degrees-of-freedom robotic manipulator articulated 18 cadaveric knees through simulations of kinematics recorded from in vivo drop vertical jump and sidestep cutting tasks. Specimens were articulated in the intact-knee and isolated-ligament conditions. After simulation, each ACL and MCL was failed in uniaxial tension along its fiber orientations. RESULTS: During a drop vertical jump simulation, the ACL experienced greater peak strain than the MCL (6.1% vs 0.4%; P < .01). The isolated ACL expressed greater peak anterior force (4.8% vs 0.3% body weight; P < .01), medial force (1.6% vs 0.4% body weight; P < .01), flexion torque (8.4 vs 0.4 N·m; P < .01), abduction torque (2.6 vs 0.3 N·m; P < .01), and adduction torque (0.5 vs 0.0 N·m; P = .03) than the isolated MCL. During failure testing, ACL specimens preferentially loaded in the anteromedial bundle failed at 637 N, while MCL failure occurred at 776 N. CONCLUSION: During controlled physiologic athletic tasks, the ACL provides greater contributions to knee restraint than the MCL, which is generally unstrained and minimally loaded. CLINICAL RELEVANCE: Current findings support that multiplanar loading during athletic tasks preferentially loads the ACL over the MCL, leaving the ACL more susceptible to injury. An enhanced understanding of joint loading during in vivo tasks may provide insight that enhances the efficacy of injury prevention protocols.

Improved biomechanical and biological outcomes in the MRL/MpJ murine strain following a full-length patellar tendon injury.

Musculoskeletal injuries greatly affect the U.S. population and current clinical approaches fail to restore long-term native tissue structure and function. Tissue engineering is a strategy advocated to improve tendon healing; however, the field still needs to establish biological benchmarks for assessing the effectiveness of tissue-engineered structures. Investigating superior healing models, such as the MRL/MpJ, offers the opportunity to first characterize successful healing and then apply experimental findings to tissue-engineered therapies. This study seeks to evaluate the MRL/MpJ's healing response following a central patellar tendon injury compared to wildtype. Gene expression and histology were assessed at 3, 7, and 14 days following injury and mechanical properties were measured at 2, 5, and 8 weeks. Native patellar tendon biological and mechanical properties were not different between strains. Following injury, the MRL/MpJ displayed increased mechanical properties between 5 and 8 weeks; however, early tenogenic expression patterns were not different between the strains. Furthermore, expression of the cyclin-dependent kinase inhibitor, p21, was not different between strains, suggesting an alternative mechanism may be driving the healing response. Future studies will investigate collagen structure and alignment of the repair tissue and characterize the complete healing transcriptome to identify mechanisms driving the MRL/MpJ response.

A Novel Methodology for the Simulation of Athletic Tasks on Cadaveric Knee Joints with Respect to In Vivo Kinematics.

Six degree of freedom (6-DOF) robotic manipulators have simulated clinical tests and gait on cadaveric knees to examine knee biomechanics. However, these activities do not necessarily emulate the kinematics and kinetics that lead to anterior cruciate ligament (ACL) rupture. The purpose of this study was to determine the techniques needed to derive reproducible, in vitro simulations from in vivo skin-marker kinematics recorded during simulated athletic tasks. Input of raw, in vivo, skin-marker-derived motion capture kinematics consistently resulted in specimen failure. The protocol described in this study developed an in-depth methodology to adapt in vivo kinematic recordings into 6-DOF knee motion simulations for drop vertical jumps and sidestep cutting. Our simulation method repeatably produced kinetics consistent with vertical ground reaction patterns while preserving specimen integrity. Athletic task simulation represents an advancement that allows investigators to examine ACL-intact and graft biomechanics during motions that generate greater kinetics, and the athletic tasks are more representative of documented cases of ligament rupture. Establishment of baseline functional mechanics within the knee joint during athletic tasks will serve to advance the prevention, repair and rehabilitation of ACL injuries.

Ablating hedgehog signaling in tenocytes during development impairs biomechanics and matrix organization of the adult murine patellar tendon enthesis.

Restoring the native structure of the tendon enthesis, where collagen fibers of the midsubstance are integrated within a fibrocartilaginous structure, is problematic following injury. As current surgical methods fail to restore this region adequately, engineers, biologists, and clinicians are working to understand how this structure forms as a prerequisite to improving repair outcomes. We recently reported on the role of Indian hedgehog (Ihh), a novel enthesis marker, in regulating early postnatal enthesis formation. Here, we investigate how inactivating the Hh pathway in tendon cells affects adult (12-week) murine patellar tendon (PT) enthesis mechanics, fibrocartilage morphology, and collagen fiber organization. We show that ablating Hh signaling resulted in greater than 100% increased failure insertion strain (0.10 v. 0.05 mm/mm, p<0.01) as well as sub-failure biomechanical deficiencies. Although collagen fiber orientation appears overtly normal in the midsubstance, ablating Hh signaling reduces mineralized fibrocartilage by 32%, leading to less collagen embedded within mineralized tissue. Ablating Hh signaling also caused collagen fibers to coalesce at the insertion, which may explain in part the increased strains. These results indicate that Ihh signaling plays a critical role in the mineralization process of fibrocartilaginous entheses and may be a novel therapeutic to promote tendon-to-bone healing.

Fibrin gels exhibit improved biological, structural, and mechanical properties compared with collagen gels in cell-based tendon tissue-engineered constructs.

The prevalence of tendon and ligament injuries and inadequacies of current treatments is driving the need for alternative strategies such as tissue engineering. Fibrin and collagen biopolymers have been popular materials for creating tissue-engineered constructs (TECs), as they exhibit advantages of biocompatibility and flexibility in construct design. Unfortunately, a few studies have directly compared these materials for tendon and ligament applications. Therefore, this study aims at determining how collagen versus fibrin hydrogels affect the biological, structural, and mechanical properties of TECs during formation in vitro. Our findings show that tendon and ligament progenitor cells seeded in fibrin constructs exhibit improved tenogenic gene expression patterns compared with their collagen-based counterparts for approximately 14 days in culture. Fibrin-based constructs also exhibit improved cell-derived collagen alignment, increased linear modulus (2.2-fold greater) compared with collagen-based constructs. Cyclic tensile loading, which promotes the maturation of tendon constructs in a previous work, exhibits a material-dependent effect in this study. Fibrin constructs show trending reductions in mechanical, biological, and structural properties, whereas collagen constructs only show improved tenogenic expression in the presence of mechanical stimulation. These findings highlight that components of the mechanical stimulus (e.g., strain amplitude or time of initiation) need to be tailored to the material and cell type. Given the improvements in tenogenic expression, extracellular matrix organization, and material properties during static culture, in vitro findings presented here suggest that fibrin-based constructs may be a more suitable alternative to collagen-based constructs for tissue-engineered tendon/ligament repair.

Anterior cruciate ligament biomechanics during robotic and mechanical simulations of physiologic and clinical motion tasks: a systematic review and meta-analysis.

Investigators use in vitro joint simulations to invasively study the biomechanical behaviors of the anterior cruciate ligament. The aims of these simulations are to replicate physiologic conditions, but multiple mechanisms can be used to drive in vitro motions, which may influence biomechanical outcomes. The objective of this review was to examine, summarize, and compare biomechanical evidence related to anterior cruciate ligament function from in vitro simulations of knee motion. A systematic review was conducted (2004 to 2013) in Scopus, PubMed/Medline, and SPORTDiscus to identify peer-reviewed studies that reported kinematic and kinetic outcomes from in vitro simulations of physiologic or clinical tasks at the knee. Inclusion criteria for relevant studies were articles published in English that reported on whole-ligament anterior cruciate ligament mechanics during the in vitro simulation of physiologic or clinical motions on cadaveric knees that were unaltered outside of the anterior-cruciate-ligament-intact, -deficient, and -reconstructed conditions. A meta-analysis was performed to synthesize biomechanical differences between the anterior-cruciate-ligament-intact and reconstructed conditions. 77 studies met our inclusion/exclusion criteria and were reviewed. Combined joint rotations have the greatest impact on anterior cruciate ligament loads, but the magnitude by which individual kinematic degrees of freedom contribute to ligament loading during in vitro simulations is technique-dependent. Biomechanical data collected in prospective, longitudinal studies corresponds better with robotic-manipulator simulations than mechanical-impact simulations. Robotic simulation indicated that the ability to restore intact anterior cruciate ligament mechanics with anterior cruciate ligament reconstructions was dependent on loading condition and degree of freedom examined.

Mechanical properties and fibrin characteristics of endovascular coil-clot complexes: relevance to endovascular cerebral aneurysm repair paradigms.

BACKGROUND: Although coil embolization is known to prevent rebleeding from acutely ruptured cerebral aneurysms, the underlying biological and mechanical mechanisms have not been characterized. We sought to determine if microcoil-dependent interactions with thrombus induce structural and mechanical changes in the adjacent fibrin network. Such changes could play an important role in the prevention of aneurysm rebleeding. METHODS: The stiffness of in vitro human blood clots and coil-clot complexes implanted into aneurysm phantoms were measured immediately after formation and after retraction for 3 days using unconfined uniaxial compression assays. Scanning electron microscopy of the coil-clot complexes showed the effect of coiling on clot structure. RESULTS: The coil packing densities achieved were in the range of clinical practice. Bare platinum coils increased clot stiffness relative to clot alone (Young's modulus 6.9 kPa and 0.83 kPa, respectively) but did not affect fibrin structure. Hydrogel-coated coils prevented formation of a clot and had no significant effect on clot stiffness (Young's modulus 2 kPa) relative to clot alone. Clot age decreased fiber density by 0.2 fibers/µm(2) but not the stiffness of the bare platinum coil-clot complex. CONCLUSIONS: The stiffness of coil-clot complexes is related to the summative stiffness of the fibrin network and associated microcoils. Hydrogel-coated coils exhibit significantly less stiffness due to the mechanical properties of the hydrogel and the inhibition of fibrin network formation by the hydrogel. These findings have important implications for the design and engineering of aneurysm occlusion devices.

Effect of ACL graft material on joint forces during a simulated in vivo motion in the porcine knee: examining force during the initial cycles.

This study compared three-dimensional forces in knees containing anterior cruciate ligament (ACL) graft materials versus the native porcine ACL. A six-degree-of-freedom (DOF) robot simulated gait while recording the joint forces and moments. Knees were subjected to 10 cycles of simulated gait in intact, ACL-deficient, and ACL-reconstructed knee states to examine time zero biomechanical performance. Reconstruction was performed using bone-patellar tendon-bone allograft (BPTB), reconstructive porcine tissue matrix (RTM), and an RTM-polymer hybrid (Hybrid). Forces and moments were examined about anatomic DOFs throughout the gait cycle and at three key points during gait: heel strike (HS), mid stance (MS), toe off (TO). Compared to native ACL, each graft restored antero-posterior (A-P) forces throughout gait. However, all failed to mimic normal joint forces in other DOFs. For example, each reconstructed knee showed greater compressive forces at HS and TO compared to the native ACL knee. Overall, the Hybrid graft restored more of the native ACL forces following reconstruction than did BPTB, while RTM grafts were the least successful. If early onset osteoarthritis is in part caused by altered knee kinematics, then understanding how reconstruction materials restore critical force generation during gait is an essential step in improving a patient's long-term prognosis.

Functional tissue engineering of tendon: Establishing biological success criteria for improving tendon repair.

Improving tendon repair using Functional Tissue Engineering (FTE) principles has been the focus of our laboratory over the last decade. Although our primary goals were initially focused only on mechanical outcomes, we are now carefully assessing the biological properties of our tissue-engineered tendon repairs so as to link biological influences with mechanics. However, given the complexities of tendon development and healing, it remains challenging to determine which aspects of tendon biology are the most important to focus on in the context of tissue engineering. To address this problem, we have formalized a strategy to identify, prioritize, and evaluate potential biological success criteria for tendon repair. We have defined numerous biological properties of normal tendon relative to cellular phenotype, extracellular matrix and tissue ultra-structure that we would like to reproduce in our tissue-engineered repairs and prioritized these biological criteria by examining their relative importance during both normal development and natural tendon healing. Here, we propose three specific biological criteria which we believe are essential for normal tendon function: (1) scleraxis-expressing cells; (2) well-organized and axially-aligned collagen fibrils having bimodal diameter distribution; and (3) a specialized tendon-to-bone insertion site. Moving forward, these biological success criteria will be used in conjunction with our already established mechanical success criteria to evaluate the effectiveness of our tissue-engineered tendon repairs.

Primary and secondary restraints of human and ovine knees for simulated in vivo gait kinematics.

Knee soft tissue structures are frequently injured, leading to the development of osteoarthritis even with treatment. Understanding how these structures contribute to knee function during activities of daily living (ADLs) is crucial in creating more effective treatments. This study was designed to determine the role of different knee structures during a simulated ADL in both human knees and ovine stifle joints. A six degree-of-freedom robot was used to reproduce each species' in vivo gait while measuring three-dimensional joint forces and torques. Using a semi-randomized selective cutting method, we determined the primary and secondary structures contributing to the forces and torques along and about each anatomical axis. In both species, the bony interaction, ACL, and medial meniscus provided most of the force contributions during stance, whereas the ovine MCL, human bone, and ACLs of both species were the key contributors during swing. This study contributes to our overarching goal of establishing functional tissue engineering parameters for knee structures by further validating biomechanical similarities between the ovine model and the human to provide a platform for measuring biomechanics during an in vivo ADL. These parameters will be used to develop more effective treatments for knee injuries to reduce or eliminate the incidence of osteoarthritis.