Patient-oriented and performance-based outcomes after knee autologous chondrocyte implantation: a timeline for the first year of recovery

It is well established that autologous chondrocyte implantation (ACI) can require extended recovery postoperatively; however, little information exists to provide clinicians and patients with a timeline for anticipated function during the first year after ACI. Objective: To document the recovery of functional performance of activities of daily living after ACI. Patients: ACI patients (n = 48, 29 male 35.1 ± 8.0 y). Intervention: All patients completed functional tests (weight-bearing squat, walk-across, sit-to-stand, step-up/over, and forward lunge) using the NeuroCom long force plate (Clackamas, OR) and completed patient-reported outcome measures (International Knee Documentation Committee Subjective Knee Evaluation Form, Lysholm, Western Ontario and McMaster Osteoarthritis Index WOMAC, and 36-Item Short-Form Health Survey) preoperatively and 3, 6, and 12 mo postoperatively. Main Outcome Measures: A covariance pattern model was used to compare performance and self-reported outcome across time and provide a timeline for functional recovery after ACI. Results: Participants demonstrated significant improvement in walk-across stride length from baseline (42.0% ± 8.9% height) at 6 (46.8% ± 8.1%) and 12 mo (46.6% ± 7.6%). Weight bearing on the involved limb during squatting at 30°, 60°, and 90° was significantly less at 3 mo than presurgery. Step-up/over time was significantly slower at 3 mo (1.67 ± 0.69 s) than at baseline (1.49 ± 0.33 s), 6 mo (1.51 ± 0.36 s), and 12 mo (1.40 ± 0.26 s). Step-up/over lift-up index was increased from baseline (41.0% ± 11.3% body weight BW) at 3 (45.0% ± 11.7% BW), 6 (47.0% ± 11.3% BW), and 12 mo (47.3% ± 11.6% BW). Forward-lunge time was decreased at 3 mo (1.51 ± 0.44 s) compared with baseline (1.39 ± 0.43 s), 6 mo (1.32 ± 0.05 s), and 12 mo (1.27 ± 0.06). Similarly, forward-lunge impact force was decreased at 3 mo (22.2% ± 1.4% BW) compared with baseline (25.4% ± 1.5% BW). The WOMAC demonstrated significant improvements at 3 mo. All patient-reported outcomes were improved from baseline at 6 and 12 mo postsurgery. Conclusions: Patients' perceptions of improvements may outpace physical changes in function. Decreased function for at least the first 3 mo after ACI should be anticipated, and improvement in performance of tasks requiring weight-bearing knee flexion, such as squatting, going down stairs, or lunging, may not occur for a year or more after surgery

Doctor of Philosophy

dissertationAltered mechanics are believed to initiate osteoarthritis in hips with acetabular dysplasia. Periacetabular osteotomy (PAO) is the preferred surgical treatment; however, it is unknown if the procedure normalizes joint anatomy and mechanics. Changes in three-dimensional (3D) morphology and chondrolabral mechanics were quantified after PAO. Finite element (FE) models demonstrated that PAO improved the distribution of coverage, reduced stress, increased congruity, and prevented cartilage thinning. However, changes in mechanics were not consistent. In fact, one patient exhibited increased stress after surgery, which was believed to be a result of over-correction. Therefore, methods to integrate morphologic and biomechanical analysis with clinical care could standardize outcomes of PAO. FE simulations are time-intensive and require significant computing resources. Therefore, the second aim was to implement an efficient method to estimate mechanics. An enhanced discrete element analysis (DEA) model of the hip that accurately incorporated cartilage geometry and efficiently calculated stress was developed and analyzed. Although DEA model estimates predicted elevated magnitudes of contact stress, the distribution corresponded well with FE models. As a computationally efficient platform, DEA could assist in diagnosis and surgical planning. Imaging is a precursor to analyzing morphology and biomechanics. Ideally, an imaging protocol would visualize bone and soft-tissue at high resolution without ionizing radiation. Magnetic resonance imaging (MRI) with 3D dual-echo-steady-state (DESS) is a promising sequence to image the hip noninvasively, but its accuracy has not been quantified. Therefore, the final aim was to implement and validate the use of 3D DESS MRI in the hip. Using direct measurements of cartilage thickness as the standard, 3D DESS MRI imaged cartilage to ~0.5 mm of the physical measurements with 95% confidence, which is comparable to the most accurate hip imaging protocol presented to date. In summary, this dissertation provided unique insights into the morphologic and biomechanical features following PAO. In the future, DEA could be combined with 3D DESS MRI to efficiently analyze contact stress distributions. These methods could be incorporated into preoperative planning software, where the algorithm would predict the optimal relocation of the acetabulum to maximize femoral head coverage while minimizing contact stress, and thereby improve long-term outcomes of PAO

Biomechanics of foetal movement.

© 2015, AO Research Institute. All rights reserved.Foetal movements commence at seven weeks of gestation, with the foetal movement repertoire including twitches, whole body movements, stretches, isolated limb movements, breathing movements, head and neck movements, jaw movements (including yawning, sucking and swallowing) and hiccups by ten weeks of gestational age. There are two key biomechanical aspects to gross foetal movements; the first being that the foetus moves in a dynamically changing constrained physical environment in which the freedom to move becomes increasingly restricted with increasing foetal size and decreasing amniotic fluid. Therefore, the mechanical environment experienced by the foetus affects its ability to move freely. Secondly, the mechanical forces induced by foetal movements are crucial for normal skeletal development, as evidenced by a number of conditions and syndromes for which reduced or abnormal foetal movements are implicated, such as developmental dysplasia of the hip, arthrogryposis and foetal akinesia deformation sequence. This review examines both the biomechanical effects of the physical environment on foetal movements through discussion of intrauterine factors, such as space, foetal positioning and volume of amniotic fluid, and the biomechanical role of gross foetal movements in human skeletal development through investigation of the effects of abnormal movement on the bones and joints. This review also highlights computational simulations of foetal movements that attempt to determine the mechanical forces acting on the foetus as it moves. Finally, avenues for future research into foetal movement biomechanics are highlighted, which have potential impact for a diverse range of fields including foetal medicine, musculoskeletal disorders and tissue engineering

Doctor of Philosophy

dissertationGeometric abnormalities of the human hip joint, as found in femoroacetabular impingement (FAI) and acetabular dysplasia, alter hip biomechanics and may be the primary causes of osteoarthritis in young adults. However, empirical evidence of direct correlations between abnormal geometry, altered biomechanics, and osteoarthritis is scarce. Also, clinical measures used to diagnose FAI and dysplasia still have substantial limitations, including questions about their reliability, assumptions about hip joint geometry and their ability to definitively distinguish pathologic from normal hips. The goals of this dissertation are twofold. First, a set of tools are presented and applied to quantify three-dimensional (3D) anatomical differences between hips with FAI and control subjects. The 3D tools were developed, validated and applied to patients with a subtype of FAI, called cam FAI, to improve basic understanding of the spectrum of FAI deformities, and to provide meaningful new metrics of morphology that are relatable to current diagnostic methods and translate easily for clinical use. The second goal of this dissertation is to improve our understanding of intra-articular hip contact mechanics as well as hip joint kinematics and muscle forces. To do so, a finite element study of intraarticular cartilage contact mechanics was completed with a cohort of live human subjects, using a validated modeling protocol. Finally, musculoskeletal modeling was used with gait data from healthy subjects and acetabular dysplasia patients to provide preliminary estimates of hip joint kinematics, kinetics, and muscle forces and compare differences between the groups. The translational methods of this dissertation utilized techniques from orthopaedics, computer science, physical therapy, mechanics, and medical imaging. Results from this dissertation offer new insight into the complex pathomechanics and pathomorphology of FAI and acetabular dysplasia. Application and extension of the work of this dissertation has the potential to help establish links between FAI and dysplasia with osteoarthritis and to improve patient care

Doctor of Philosophy

dissertationWhile the healthy hip provides decades of pain free articulation, the cartilage and labrum may degenerate during the process of osteoarthritis (OA). Most hip OA is caused by subtle pathomorphologies, including acetabular dysplasia and acetabular retroversion. The link between pathomorphology and OA is thought to be mechanical, but the mechanics have not been quantified. The aim of this dissertation was to provide insight into the pathogenesis of hip OA via finite element (FE) modeling. The objectives were two-fold: to validate a subject-specific modeling protocol for a series of specimens and assess the effects of assumptions on model predictions, and to use the modeling protocol to evaluate soft tissue mechanics in pathomorphologic hips in comparison to normal hips. For the first objective, FE predictions of contact stress and contact area were directly validated for five cadaveric specimens, and the specimen- and region-specific hyperelastic material behavior of cartilage was determined. FE predictions of contact stress and contact area were in good agreement with experimental results, and were relatively insensitive to the assumed cartilage constitutive model. There were distinct regional differences in the hyperelastic material behavior of human hip cartilage, with stiffer lateral than medial cartilage and stiffer acetabular than femoral cartilage. In order to investigate the mechanical link between pathomorphology and hip OA, FE models of ten hips with normal morphology, ten hips with acetabular dysplasia and ten hips with acetabular retroversion were generated. FE models of dysplastic acetabula demonstrated the importance of the acetabular labrum in load support in the dysplastic hip. FE models of retroverted acetabula demonstrated distinct superomedial contact patterns in comparison to distributed contact patterns in the normal hip. Finally, the effects of cartilage constitutive model on predictions of transchondral maximum shear stress and first principal strain were evaluated. In contrast to contact stress and contact area, maximum shear stress and first principal strain were sensitive to the cartilage constitutive model. Overall, this dissertation provides novel insights into the contact mechanics of pathomorphologic hips that may be important in the pathogenesis of OA, as well as the technical foundation for studies evaluating additional mechanical variables in the human hip

Correlates and consequences of varus knee thrust in osteoarthritis

Varus knee thrust is an abnormal frontal-plane movement (i.e., an out-bowing) of the knee that occurs during the weight-acceptance phase of gait. Varus thrust is of clinical interest, as it is a potentially-modifiable biomechanical risk factor for knee osteoarthritis (OA) progression and has been associated with knee pain. The overall aim of this dissertation is to identify the structural and symptomatic consequences of varus thrust at the knee and along the lower limb, and the possible anatomical and sensorimotor causes of varus thrust in older adults with or at risk for OA. Varus thrust was assessed in Multicenter Osteoarthritis (MOST) Study participants using high-speed videos of self-paced walking. Varus thrust was observed in 31.3% of 3730 knees. We investigated the longitudinal relation of varus thrust to MRI lesions and found that thrust was associated with increased odds of incident and worsening bone marrow lesions and worsening cartilage loss. We then investigated the longitudinal association of varus thrust with WOMAC knee pain and found that thrust was associated with increased odds of incident and worsening total WOMAC knee pain and worsening pain during weight-bearing and non-weight bearing activities. In an ancillary quantitative gait analysis of a single subject with unilateral varus thrust, we found altered joint moments at the hip, knee, and ankle in the thrust limb compared to the non-thrust limb. We bolstered this pilot data with an investigation of low back and lower extremity pain in the presence of thrust in MOST participants: limbs with thrust had increased odds of incident frequent pain proximal (hip or low back) and distal (ankle and foot) to the knee compared to limbs without thrust. Finally, we investigated the cross-sectional relation of anatomical and sensorimotor impairments at the knee and lower extremity to the prevalence of varus thrust. Thrust was most prevalent in limbs with static varus malalignment and supinated feet during gait, while increasing static knee laxity had a protective effect against thrust. These results fill substantial gaps in the narrative regarding the role of varus thrust in OA development

Future directions for the management of pain in osteoarthritis.

Osteoarthritis (OA) is the predominant form of arthritis worldwide, resulting in a high degree of functional impairment and reduced quality of life owing to chronic pain. To date, there are no treatments that are known to modify disease progression of OA in the long term. Current treatments are largely based on the modulation of pain, including NSAIDs, opiates and, more recently, centrally acting pharmacotherapies to avert pain. This review will focus on the rationale for new avenues in pain modulation, including inhibition with anti-NGF antibodies and centrally acting analgesics. The authors also consider the potential for structure modification in cartilage/bone using growth factors and stem cell therapies. The possible mismatch between structural change and pain perception will also be discussed, introducing recent techniques that may assist in improved patient phenotyping of pain subsets in OA. Such developments could help further stratify subgroups and treatments for people with OA in future

Biomechanics

Biomechanics is a vast discipline within the field of Biomedical Engineering. It explores the underlying mechanics of how biological and physiological systems move. It encompasses important clinical applications to address questions related to medicine using engineering mechanics principles. Biomechanics includes interdisciplinary concepts from engineers, physicians, therapists, biologists, physicists, and mathematicians. Through their collaborative efforts, biomechanics research is ever changing and expanding, explaining new mechanisms and principles for dynamic human systems. Biomechanics is used to describe how the human body moves, walks, and breathes, in addition to how it responds to injury and rehabilitation. Advanced biomechanical modeling methods, such as inverse dynamics, finite element analysis, and musculoskeletal modeling are used to simulate and investigate human situations in regard to movement and injury. Biomechanical technologies are progressing to answer contemporary medical questions. The future of biomechanics is dependent on interdisciplinary research efforts and the education of tomorrow’s scientists