Free Achilles tendon strain during selected rehabilitation, locomotor, jumping, and landing tasks.

A better understanding of the strains experienced by the Achilles tendon during commonly prescribed exercises and locomotor tasks is needed to improve efficacy of Achilles tendon training and rehabilitation programs. The aim of this study was to estimate in vivo free Achilles tendon strain during selected rehabilitation, locomotor, jumping, and landing tasks. Sixteen trained runners with no symptoms of Achilles tendinopathy participated in this study. Personalized free Achilles tendon moment arm and force-strain curve were obtained from imaging data and used in conjunction with motion capture and surface electromyography to estimate free Achilles tendon strain using electromyogram-informed neuromusculoskeletal modeling. There was a strong correspondence between Achilles tendon force estimates from the present study and experimental data reported in the literature (R2 > 0.85). The average tendon strain was highest for maximal hop landing (8.8 ± 1.6%), lowest for walking at 1.4 m/s (3.1 ± 0.8%), and increased with locomotor speed during running (run 3.0 m/s: 6.5 ± 1.6%; run 5.0 m/s: 7.9 ± 1.7%) and during heel rise exercise with added mass (BW: 5.8 ± 1.3%; 1.2 BW: 6.9 ± 1.7%). The peak tendon strain was highest during running (5 m/s: 13.7 ± 2.5%) and lowest during walking (1.4 m/s: 7 ± 1.8%). Overall findings provide a preliminary evidence base for exercise selection to maximize anabolic tendon remodeling during training and rehabilitation of the Achilles tendon.NEW & NOTEWORTHY Our work combines medical imaging and electromyogram-informed neuromusculoskeletal modeling data to estimate free Achilles tendon strain during selected rehabilitation, locomotor, jumping, and landing tasks in trained middle-distance runners. These data may potentially be used to inform Achilles tendon training and rehabilitation to maximize anabolic tendon remodeling.

A Novel In Vitro and In Silico System for Analyzing Complex Mechanobiological Behavior of Chondrocytes in Three-Dimensional Hydrogel Constructs.

Physiological loading is essential for the maintenance of articular cartilage through the regulation of tissue remodeling. To correctly understand the behavior of chondrocytes in their native environment, cell stimulating devices and bioreactors have been developed to examine the effect of mechanical stimuli on chondrocytes. This study describes the design and validation of a novel system for analyzing chondrocyte deformation patterns. This involves an in vitro mechanical device for a controlled application of multi-axial-loading regimes to chondrocyte-seeded agarose constructs and in silico models for analyzing chondrocyte deformation patterns. The computer-controlled device precisely applies compressive, tensile, and shear strains to hydrogel constructs using a customizable macro-based program. The synchronization of the displacements is shown to be accurate with a 1.2% error and is highly reproducible. The device design allows housing for up to eight novel designed free-swelling three-dimensional hydrogel constructs. Constructs include mesh ends and are optimized to withstand the application of up to 7% mechanical tensile and 15% shear strains. Constructs were characterized through mapping the strain within as mechanical load was applied and was validated using light microscopy methods, chondrocyte viability using live/dead imaging, and cell deformation strains. Images were then analyzed to determine the complex deformation strain patterns of chondrocytes under a range of dynamic mechanical stimulations. This is one of the first systems that have characterized construct strains to cellular strains. The features in this device make the system ideally suited for a systematic approach for the investigation of the response of chondrocytes to a complex physiologically relevant deformation profile.

Targeted Achilles Tendon Training and Rehabilitation Using Personalized and Real-Time Multiscale Models of the Neuromusculoskeletal System.

Musculoskeletal tissues, including tendons, are sensitive to their mechanical environment, with both excessive and insufficient loading resulting in reduced tissue strength. Tendons appear to be particularly sensitive to mechanical strain magnitude, and there appears to be an optimal range of tendon strain that results in the greatest positive tendon adaptation. At present, there are no tools that allow localized tendon strain to be measured or estimated in training or a clinical environment. In this paper, we first review the current literature regarding Achilles tendon adaptation, providing an overview of the individual technologies that so far have been used in isolation to understand in vivo Achilles tendon mechanics, including 3D tendon imaging, motion capture, personalized neuromusculoskeletal rigid body models, and finite element models. We then describe how these technologies can be integrated in a novel framework to provide real-time feedback of localized Achilles tendon strain during dynamic motor tasks. In a proof of concept application, Achilles tendon localized strains were calculated in real-time for a single subject during walking, single leg hopping, and eccentric heel drop. Data was processed at 250 Hz and streamed on a smartphone for visualization. Achilles tendon peak localized strains ranged from ∼3 to ∼11% for walking, ∼5 to ∼15% during single leg hop, and ∼2 to ∼9% during single eccentric leg heel drop, overall showing large strain variation within the tendon. Our integrated framework connects, across size scales, knowledge from isolated tendons and whole-body biomechanics, and offers a new approach to Achilles tendon rehabilitation and training. A key feature is personalization of model components, such as tendon geometry, material properties, muscle geometry, muscle-tendon paths, moment arms, muscle activation, and movement patterns, all of which have the potential to affect tendon strain estimates. Model personalization is important because tendon strain can differ substantially between individuals performing the same exercise due to inter-individual differences in these model components.

Influence of altered geometry and material properties on tissue stress distribution under load in tendinopathic Achilles tendons - A subject-specific finite element analysis.

Achilles tendon material properties and geometry are altered in Achilles tendinopathy. The purpose of this study was to determine the relative contributions of altered material properties and geometry to free Achilles tendon stress distribution during a sub-maximal contraction in tendinopathic relative to healthy tendons. Tendinopathic (n = 8) and healthy tendons (n = 8) were imaged at rest and during a sub-maximal voluntary isometric contraction using three-dimensional freehand ultrasound. Images were manually segmented and used to create subject-specific finite element models. The resting cross-sectional area of the free tendon was on average 31% greater for the tendinopathic compared to healthy tendons. Material properties for each tendon were determined using a numerical parameter optimisation approach that minimised the difference in experimentally measured longitudinal strain and the strain predicted by the finite element model under submaximal loading conditions for each tendon. The mean Young's modulus for tendinopathic tendons was 53% lower than the corresponding control value. Finite element analyses revealed that tendinopathic tendons experience 24% less stress under the same submaximal external loading conditions compared to healthy tendons. The lower tendon stress in tendinopathy was due to a greater influence of tendon cross-sectional area, which alone reduced tendon stress by 30%, compared to a lower Young's modulus, which alone increased tendon stress by 8%. These findings suggest that the greater tendon cross-sectional area observed in tendinopathy compensates for the substantially lower Young's modulus, thereby protecting pathological tendon against excessive stress.

Combining in silico and in vitro experiments to characterize the role of fascicle twist in the Achilles tendon.

The Achilles tendon (AT), the largest tendon in the human body has a unique structural feature, that is the fascicles in the AT display spiral twist. However, their functional and structural roles are still unclear. We used subject-specific computational models and tissue mechanical experiment to quantitatively characterize the role of fascicle twist in the Achilles tendon. Ten subject-specific finite element (FE) models of the Achilles tendon were developed from ultrasound images. Fascicle twist was implemented in these models using the material coordinate system available in our FE framework. Five different angles (0~60°) were implemented and material property optimization was performed for each of them (total 50 sets) using results from uniaxial stretch experiment. We showed that fascicle twist allows for even distribution of stress across the whole tendon, thus improving tissue strength. The predicted rupture load increased up to 40%. A number of connective tissues display similar fascicle twists in their structure. The resulting non-uniform strain distribution has been hypothesized as a primary factor in tissue degeneration and injuries. Therefore, our technique will be used to design biomechanically informed training and rehabilitation protocols for management of connective tissue injuries and degeneration.

Achilles tendon stress is more sensitive to subject-specific geometry than subject-specific material properties: A finite element analysis.

This study used subject-specific measures of three-dimensional (3D) free Achilles tendon geometry in conjunction with a finite element method to investigate the effect of variation in subject-specific geometry and subject-specific material properties on tendon stress during submaximal isometric loading. Achilles tendons of eight participants (Aged 25-35years) were scanned with freehand 3D ultrasound at rest and during a 70% maximum voluntary isometric contraction. Ultrasound images were segmented, volume rendered and transformed into subject-specific 3D finite element meshes. The mean (±SD) lengths, volumes and cross-sectional areas of the tendons at rest were 62±13mm, 3617±984mm3 and 58±11mm2 respectively. The measured tendon strain at 70% MVIC was 5.9±1.3%. Subject-specific material properties were obtained using an optimisation approach that minimised the difference between measured and modelled longitudinal free tendon strain. Generic geometry was represented by the average mesh and generic material properties were taken from the literature. Local stresses were subsequently computed for combinations of subject-specific and generic geometry and material properties. For a given geometry, changing from generic to subject-specific material properties had little effect on the stress distribution in the tendon. In contrast, changing from generic to subject-specific geometry had a 26-fold greater effect on tendon stress distribution. Overall, these findings indicate that the stress distribution experienced by the living free Achilles tendon of a young and healthy population during voluntary loading are more sensitive to variation in tendon geometry than variation in tendon material properties.

Applying Physiologically Relevant Strains to Tenocytes in an In Vitro Cell Device Induces In Vivo Like Behaviors.

We have developed a novel cell stretching device (called Cell Gym) capable of applying physiologically relevant low magnitude strains to tenocytes on a collagen type I coated membrane. We validated our device thoroughly on two levels: (1) substrate strains, (2) cell level strains. Our cell level strain results showed that the applied stretches were transferred to cells accurately (∼90%). Our gene expression data showed that mechanically stimulated tenocytes (4%) expressed a lower level of COL I gene. COX2 gene was increased but did not reach statistical significance. Our device was then tested to see if it could reproduce results from an in vivo study that measured time-dependent changes in collagen synthesis. Our results showed that collagen synthesis peaked at 24 hrs after exercise and then decreased, which matched the results from the in vivo study. Our study demonstrated that it is important to incorporate physiologically relevant low strain magnitudes in in vitro cell mechanical studies and the need to validate the device thoroughly to operate the device at small strains. This device will be used in designing novel tendon tissue engineering scaffolds in the future.

The influence and biomechanical role of cartilage split line pattern on tibiofemoral cartilage stress distribution during the stance phase of gait.

This study presents an evaluation of the role that cartilage fibre 'split line' orientation plays in informing femoral cartilage stress patterns. A two-stage model is presented consisting of a whole knee joint coupled to a tissue-level cartilage model for computational efficiency. The whole joint model may be easily customised to any MRI or CT geometry using free-form deformation. Three 'split line' patterns (medial-lateral, anterior-posterior and random) were implemented in a finite element model with constitutive properties referring to this 'split line' orientation as a finite element fibre field. The medial-lateral orientation was similar to anatomy and was derived from imaging studies. Model predictions showed that 'split lines' are formed along the line of maximum principal strains and may have a biomechanical role of protecting the cartilage by limiting the cartilage deformation to the area of higher cartilage thickness.

Analyzing bone remodeling patterns after total hip arthroplasty using quantitative computed tomography and patient-specific 3D computational models.

BACKGROUND: Computational models in the form of finite element analysis technique that incorporates bone remodeling theories along with DEXA scans has been extensively used in predicting bone remodeling patterns around the implant. However, majority of such studies used generic models. Therefore, the aim of this study is to develop patient-specific finite element models of total hip replacement patients using their quantitative computed tomography (QCT) scans and accurately analyse bone remodelling patterns after total hip arthroplasty (THA). METHODS: Patient-specific finite element models have been generated using the patients' QCT scans from a previous clinical follow-up study. The femur was divided into five regions in proximal-distal direction and then further divided into four quadrants for detailed analysis of bone remodeling patterns. Two types of analysis were performed-inter-patient and intra patient to compare them and then the resulting bone remodeling patterns were quantitatively analyzed. RESULTS: Our results show that cortical bone density decrease is higher in diaphyseal region over time and the cancellous bone density decreases significantly in metaphyseal region over time. In metaphyseal region, posterior-medial (P-M) quadrant showed high bone loss while diaphyseal regions show high bone loss in anterior-lateral (A-L) quadrant. CONCLUSIONS: Our study demonstrated that combining QCT with 3D patient-specific models has the ability of monitoring bone density change patterns after THA in much finer details. Future studies include using these findings for the development of a bone remodelling algorithm capable of predicting surgical outcomes for THA patients.

Validation of an efficient method of assigning material properties in finite element analysis of pelvic bone.

Bone in the pelvis is a composite material with a complex anatomical structure that is difficult to model computationally. Rather than assigning material properties to increasingly smaller elements to capture detail in three-dimensional finite element (FE) models, properties can be assigned to Gauss points within larger elements. As part of a validation process, we compared experimental and analytical results from a composite beam under four-point load to FE models with material properties assigned to refined elements and Gauss points within larger elements. Both FE models accurately predicted deformation and the analytical predictions of internal shear stress.

Subject-specific finite element analysis to characterize the influence of geometry and material properties in Achilles tendon rupture.

Achilles tendon injuries including rupture are one of the most frequent musculoskeletal injuries, but the mechanisms for these injuries are still not fully understood. Previous in vivo and experimental studies suggest that tendon rupture mainly occurs in the tendon mid-section and predominantly more in men than women due to reasons yet to be identified. Therefore we aimed to investigate possible mechanisms for tendon rupture using finite element (FE) analysis. Specifically, we have developed a framework for generating subject-specific FE models of human Achilles tendon. A total of ten 3D FE models of human Achilles tendon were generated. Subject-specific geometries were obtained using ultrasound images and a mesh morphing technique called Free Form Deformation. Tendon material properties were obtained by performing material optimization that compared and minimized difference in uniaxial tension experimental results with model predictions. Our results showed that both tendon geometry and material properties are highly subject-specific. This subject-specificity was also evident in our rupture predictions as the locations and loads of tendon ruptures were different in all specimens tested. A parametric study was performed to characterize the influence of geometries and material properties on tendon rupture. Our results showed that tendon rupture locations were dependent largely on geometry while rupture loads were more influenced by tendon material properties. Future work will investigate the role of microstructural properties of the tissue on tendon rupture and degeneration by using advanced material descriptions.

Altered load transfer in the pelvis in the presence of periprosthetic osteolysis.

Periprosthetic osteolysis in the retroacetabular region with cancellous bone loss is a recognized phenomenon in the long-term follow-up of total hip replacement. The effects on load transfer in the presence of defects are less well known. A validated, patient-specific, 3D finite element (FE) model of the pelvis was used to assess changes in load transfer associated with periprosthetic osteolysis adjacent to a cementless total hip arthroplasty (THA) component. The presence of a cancellous defect significantly increased (p < 0.05) von Mises stress in the cortical bone of the pelvis during walking and a fall onto the side. At loads consistent with single leg stance, this was still less than the predicted yield stress for cortical bone. During higher loads associated with a fall onto the side, highest stress concentrations occurred in the superior and inferior pubic rami and in the anterior column of the acetabulum with larger cancellous defects.

Finite element analysis of retroacetabular osteolytic defects following total hip replacement.

Periprosthetic osteolysis in the retroacetabular region with cancellous bone loss is a recognized phenomenon in the long-term follow-up of total hip replacement. The effects on load transfer in the presence of defects are less well known. A finite element model incorporating a retroacetabular defect behind a cementless component was validated against a 4th generation sawbone pelvis. Computational predictions of surface strain and von Mises stresses were closely correlated to experimental findings. The presence of a cancellous defect increased von Mises stress in the cortical bone of the medial wall of the pelvis. At a load of 600 N this was under the predicted failure stress for cortical bone. Increases in the cup size relative to the acetabulum caused increased stress in the cortical bone of the lateral wall of the pelvis, adjacent to the acetabulum. We are confident that our modeling approach can be applied to patient specific defects to predict pelvis stress with large loads and a range of activities.

Quantitative CT with finite element analysis: towards a predictive tool for bone remodelling around an uncemented tapered stem.

PURPOSE: We used quantitative CT in conjunction with finite element analysis to provide a new tool for assessment of bone quality after total hip arthroplasty in vivo. The hypothesis of this prospective five-year study is that the combination of the two modalities allows 3D patient-specific imaging of cortical and cancellous bone changes and stress shielding. METHOD: We tested quantitative CT in conjunction with finite elements on a cohort of 29 patients (31 hips) who have been scanned postoperatively and at one year, two years and five years follow-up. The method uses cubic Hermite finite element interpolation for efficient mesh generation directly from qCT datasets. The element Gauss points that are used for the geometric interpolation functions are also used for interpolation of osteodensitometry data. RESULTS: The study showed changes of bone density suggestive of proximal femur diaphysis load transfer with osteointegration and moderate metaphyseal stress shielding. Our model revealed that cortical bone initially became porous in the greater trochanter, but this phenomenon progressed to the cortex of the lesser trochanter and the posterior aspect of the metaphysis. The diaphyseal area did not experience major change in bone density for either cortical or cancellous bone. CONCLUSION: The combination of quantitative CT with finite element analysis allows visualization of changes to bone density and architecture. It also provides correlation of bone density/architectural changes with stress patterns enabling the study of the effects of stress shielding on bone remodelling in vivo. This technology can be useful in predicting bone remodeling and the quality of implant fixation using prostheses with different design and/or biomaterials.

Integrating degenerative mechanisms in bone and cartilage: a multiscale approach.

At the whole organ level, degenerative mechanisms in bone and cartilage are primarily attributed to modifications in loading pattern. Either a change in magnitude or location can initiate a degenerative path. At the micro scale we often see changes in structure such as porosity increase in bone and fibrillation in cartilage. These changes contribute to a reduced structural integrity that weakens the bulk strength of tissue. Finally, at the cell level we have modeling and remodeling pathways that may be disrupted through disease, drugs and altered stimulus from the micro and macro scales. In order to understand this entire process and the roles each level plays a multiscale modeling framework is necessary. This framework can take whole body loadings and pass information through finer spatial scales in order to understand how everyday dynamic movements influence micro and cellular response. In a similar manner, cellular and microstructural processes regulate whole bulk properties and modify whole organ strength. In this study we highlight the multiscale links developed as part of the open-source ontologies for the Physiome Project using the lower limb as an example. We consider the influence of remodeling in (i) anabolic treatments in cortical bone; and (ii) subchondral bone and cartilage degeneration.

A multiscale framework based on the physiome markup languages for exploring the initiation of osteoarthritis at the bone-cartilage interface.

The initiation of osteoarthritis (OA) has been linked to the onset and progression of pathologic mechanisms at the cartilage-bone interface. Most importantly, this degenerative disease involves cross-talk between the cartilage and subchondral bone environments, so an informative model should contain the complete complex. In order to evaluate this process, we have developed a multiscale model using the open-source ontologies developed for the Physiome Project with cartilage and bone descriptions at the cellular, micro, and macro levels. In this way, we can effectively model the influence of whole body loadings at the macro level and the influence of bone organization and architecture at the micro level, and have cell level processes that determine bone and cartilage remodeling. Cell information is then passed up the spatial scales to modify micro architecture and provide a macro spatial characterization of cartilage inflammation. We evaluate the framework by linking a common knee injury (anterior cruciate ligament deficiency) to proinflammatory mediators as a possible pathway to initiate OA. This framework provides a "virtual bone-cartilage" tool for evaluating hypotheses, treatment effects, and disease onset to inform and strengthen clinical studies.

Femoral bone density changes after total hip arthroplasty with uncemented taper-design stem: a five year follow-up study.

We measured bone density (BD) changes to assess adaptive bone remodelling five years after uncemented total hip arthroplasty with taper-design femoral component using quantitative computed-tomography-assisted osteodensitometry (qCT). Nineteen consecutive patients (21 hips) with degenerative joint disease were enrolled in the study. A press-fit cup and a tapered uncemented stem ceramic-ceramic pairing were used in all patients. Serial clinical, radiological and qCT osteodensitometry assessments were performed after the index operation and at the one, two and five year follow-ups. At the latest follow-up, the clinical outcome was rated satisfactory in all hips. The radiological assessment showed signs of osteointegration with stable fixation of all cups and stems. Overall, there was evidence of a BD loss at year five (p = 0.004). We estimate that BD loss was between 2.2% and 12.1% in comparison with baseline postoperative values. Progressive loss of BD in the metaphyseal region was observed in all hips. We found unremarkable BD changes of diaphyseal cortical BD throughout the five year follow-up period. qCT osteodensitometry technology allows differentiation of cortical and cancellous BD changes over time. Periprosthetic BD changes at the five year follow-up are suggestive of stable stem osteointegration with proximal femoral diaphysis load transfer and metaphyseal stress shielding.

Development and validation of patient-specific finite element models of the hemipelvis generated from a sparse CT data set.

To produce a patient-specific finite element (FE) model of a bone such as the pelvis, a complete computer tomographic (CT) or magnetic resonance imaging (MRI) geometric data set is desirable. However, most patient data are limited to a specific region of interest such as the acetabulum. We have overcome this problem by providing a hybrid method that is capable of generating accurate FE models from sparse patient data sets. In this paper, we have validated our technique with mechanical experiments. Three cadaveric embalmed pelves were strain gauged and used in mechanical experiments. FE models were generated from the CT scans of the pelves. Material properties for cancellous bone were obtained from the CT scans and assigned to the FE mesh using a spatially varying field embedded inside the mesh while other materials used in the model were obtained from the literature. Although our FE meshes have large elements, the spatially varying field allowed them to have location dependent inhomogeneous material properties. For each pelvis, five different FE meshes with a varying number of patient CT slices (8-12) were generated to determine how many patient CT slices are needed for good accuracy. All five mesh types showed good agreement between the model and experimental strains. Meshes generated with incomplete data sets showed very similar stress distributions to those obtained from the FE mesh generated with complete data sets. Our modeling approach provides an important step in advancing the application of FE models from the research environment to the clinical setting.

The use of sparse CT datasets for auto-generating accurate FE models of the femur and pelvis.

The finite element (FE) method when coupled with computed tomography (CT) is a powerful tool in orthopaedic biomechanics. However, substantial data is required for patient-specific modelling. Here we present a new method for generating a FE model with a minimum amount of patient data. Our method uses high order cubic Hermite basis functions for mesh generation and least-square fits the mesh to the dataset. We have tested our method on seven patient data sets obtained from CT assisted osteodensitometry of the proximal femur. Using only 12 CT slices we generated smooth and accurate meshes of the proximal femur with a geometric root mean square (RMS) error of less than 1 mm and peak errors less than 8 mm. To model the complex geometry of the pelvis we developed a hybrid method which supplements sparse patient data with data from the visible human data set. We tested this method on three patient data sets, generating FE meshes of the pelvis using only 10 CT slices with an overall RMS error less than 3 mm. Although we have peak errors about 12 mm in these meshes, they occur relatively far from the region of interest (the acetabulum) and will have minimal effects on the performance of the model. Considering that linear meshes usually require about 70-100 pelvic CT slices (in axial mode) to generate FE models, our method has brought a significant data reduction to the automatic mesh generation step. The method, that is fully automated except for a semi-automatic bone/tissue boundary extraction part, will bring the benefits of FE methods to the clinical environment with much reduced radiation risks and data requirement.