Ginu U. Unnikrishnan

Correlations between local strains and tissue phenotypes in an experimental model of skeletal healing.

Defining how mechanical cues regulate tissue differentiation during skeletal healing can benefit treatment of orthopaedic injuries and may also provide insight into the influence of the mechanical environment on skeletal development. Different global (i.e., organ-level) mechanical loads applied to bone fractures or osteotomies are known to result in different healing outcomes. However, the local stimuli that promote formation of different skeletal tissues have yet to be established. Finite element analyses can estimate local stresses and strains but require many assumptions regarding tissue material properties and boundary conditions. This study used an experimental approach to investigate relationships between the strains experienced by tissues in a mechanically stimulated osteotomy gap and the patterns of tissue differentiation that occur during healing. Strains induced by the applied, global mechanical loads were quantified on the mid-sagittal plane of the callus using digital image correlation. Strain fields were then compared to the distribution of tissue phenotypes, as quantified by histomorphometry, using logistic regression. Significant and consistent associations were found between the strains experienced by a region of the callus and the tissue type present in that region. Specifically, the probability of encountering cartilage increased, and that of encountering woven bone decreased, with increasing octahedral shear strain and, to a lesser extent, maximum principal strain. Volumetric strain was the least consistent predictor of tissue type, although towards the end of the four-week stimulation timecourse, cartilage was associated with increasingly negative volumetric strains. These results indicate that shear strain may be an important regulator of tissue fate during skeletal healing.

An Integrated Musculoskeletal-Finite-Element Model to Evaluate Effects of Load Carriage on the Tibia During Walking

Prior studies have assessed the effects of load carriage on the tibia. Here, we expand on these studies and investigate the effects of load carriage on joint reaction forces (JRFs) and the resulting spatiotemporal stress/strain distributions in the tibia. Using full-body motion and ground reaction forces from a female subject, we computed joint and muscle forces during walking for four load carriage conditions. We applied these forces as physiological loading conditions in a finite-element (FE) analysis to compute strain and stress. We derived material properties from computed tomography (CT) images of a sex-, age-, and body mass index-matched subject using a mesh morphing and mapping algorithm, and used them within the FE model. Compared to walking with no load, the knee JRFs were the most sensitive to load carriage, increasing by as much as 26.2% when carrying a 30% of body weight (BW) load (ankle: 16.4% and hip: 19.0%). Moreover, our model revealed disproportionate increases in internal JRFs with increases in load carriage, suggesting a coordinated adjustment in the musculature functions in the lower extremity. FE results reflected the complex effects of spatially varying material properties distribution and muscular engagement on tibial biomechanics during walking. We observed high stresses on the anterior crest and the medial surface of the tibia at pushoff, whereas high cumulative stress during one walking cycle was more prominent in the medioposterior aspect of the tibia. Our findings reinforce the need to include: (1) physiologically accurate loading conditions when modeling healthy subjects undergoing short-term exercise training and (2) the duration of stress exposure when evaluating stress-fracture injury risk. As a fundamental step toward understanding the instantaneous effect of external loading, our study presents a means to assess the relationship between load carriage and bone biomechanics.

Untangling the Effect of Head Acceleration on Brain Responses to Blast Waves

Multiple injury-causing mechanisms, such as wave propagation, skull flexure, cavitation, and head acceleration, have been proposed to explain blast-induced traumatic brain injury (bTBI). An accurate, quantitative description of the individual contribution of each of these mechanisms may be necessary to develop preventive strategies against bTBI. However, to date, despite numerous experimental and computational studies of bTBI, this question remains elusive. In this study, using a two-dimensional (2D) rat head model, we quantified the contribution of head acceleration to the biomechanical response of brain tissues when exposed to blast waves in a shock tube. We compared brain pressure at the coup, middle, and contre-coup regions between a 2D rat head model capable of simulating all mechanisms (i.e., the all-effects model) and an acceleration-only model. From our simulations, we determined that head acceleration contributed 36-45% of the maximum brain pressure at the coup region, had a negligible effect on the pressure at the middle region, and was responsible for the low pressure at the contre-coup region. Our findings also demonstrate that the current practice of measuring rat brain pressures close to the center of the brain would record only two-thirds of the maximum pressure observed at the coup region. Therefore, to accurately capture the effects of acceleration in experiments, we recommend placing a pressure sensor near the coup region, especially when investigating the acceleration mechanism using different experimental setups.

Differences in Trabecular Microarchitecture and Simplified Boundary Conditions Limit the Accuracy of QCT-based Finite Element Models of Vertebral Failure

Vertebral fractures are common in the elderly, but efforts to reduce their incidence have been hampered by incomplete understanding of the failure processes that are involved. This studys goal was to elucidate failure processes in the lumbar vertebra and to assess the accuracy of quantitative computed tomography (QCT)-based finite element (FE) simulations of these processes. Following QCT scanning, spine segments (n = 27) consisting of L1 with adjacent intervertebral disks and neighboring endplates of T12 and L2 were compressed axially in a stepwise manner. A microcomputed tomography scan was performed at each loading step. The resulting time-lapse series of images was analyzed using digital volume correlation (DVC) to quantify deformations throughout the vertebral body. While some diversity among vertebrae was observed on how these deformations progressed, common features were large strains that developed progressively in the superior third and, concomitantly, in the midtransverse plane, in a manner that was associated with spatial variations in microstructural parameters such as connectivity density. Results of FE simulations corresponded qualitatively to the measured failure patterns when boundary conditions were derived from DVC displacements at the endplate. However, quantitative correspondence was often poor, particularly when boundary conditions were simplified to uniform compressive loading. These findings suggest that variations in trabecular microstructure are one cause of the differences in failure patterns among vertebrae and that both the lack of incorporation of these variations into QCT-based FE models and the oversimplification of boundary conditions limit the accuracy of these models in simulating vertebral failure.

Material Properties of Rat Middle Cerebral Arteries at High Strain Rates

Traumatic brain injury (TBI), resulting from either impact- or non-impact blast-related mechanisms, is a devastating cause of death and disability. The cerebral blood vessels, which provide critical support for brain tissue in both health and disease, are commonly injured in TBI. However, little is known about how vessels respond to traumatic loading, particularly at rates relevant to blast. To better understand vessel responses to trauma, the objective of this project was to characterize the high-rate response of passive cerebral arteries. Rat middle cerebral arteries were isolated and subjected to high-rate deformation in the axial direction. Vessels were perfused at physiological pressures and stretched to failure at strain rates ranging from approximately 100 to 1300 s-1. Although both in vivo stiffness and failure stress increased significantly with strain rate, failure stretch did not depend on rate.

Assessment of the Effectiveness of Combat Eyewear Protection Against Blast Overpressure

It is unclear whether combat eyewear used by U. S. Service members is protective against blast overpressures (BOPs) caused by explosive devices. Here, we investigated the mechanisms by which BOP bypasses eyewear and increases eye surface pressure. We performed experiments and developed three-dimensional (3D) finite element (FE) models of a head form (HF) equipped with an advanced combat helmet (ACH) and with no eyewear, spectacles, or goggles in a shock tube at three BOPs and five head orientations relative to the blast wave. Overall, we observed good agreement between experimental and computational results, with average discrepancies in impulse and peak-pressure values of less than 15% over 90 comparisons. In the absence of eyewear and depending on the head orientation, we identified three mechanisms that contributed to pressure loading on the eyes. Eyewear was most effective at 0 deg orientation, with pressure attenuation ranging from 50 (spectacles) to 80% (goggles) of the peak pressures observed in the no-eyewear configuration. Spectacles and goggles were considerably less effective when we rotated the HF in the counter-clockwise direction around the superior-inferior axis of the head. Surprisingly, at certain orientations, spectacles yielded higher maximum pressures (80%) and goggles yielded larger impulses (150%) than those observed without eyewear. The findings from this study will aid in the design of eyewear that provides better protection against BOP.

Computational multiscale methods for tissue biomechanics

In the field of biomechanics and life sciences, tissue modelling and simulation can be surely considered as a frontier and challenging task. Both mineralized (e.g., bone, tooth enamel and dentin, cartilage) and soft tissues (e.g., skin, muscles, tendons, ligaments, blood vessels) exhibit a precise structured and hierarchical arrangement, characterized by organized biostructures with different length scales (from nano up to the macroscale) [1,2]. This is the case of collagen fibrils and fibers in soft connective tissues, of actin and myosin myofibrils in muscle’s sarcomere, of collagen lamellae in bone’s osteon. Tissue mechanics and physiological functions are highly affected by such a hierarchical and multiscale organization, as well as by a number of coupled biochemical and mechanobiological processes. Moreover, tissue disorders and diseases can be generally related with histological and biochemical alterations at different scales (e.g., [3-5]). The key goal of in-silico approaches in the field of tissue biomechanics is to develop computational methods and models that are able to integrate structural properties of the tissue and its physiological functions. In this way, reliable, predictive and patient-specific biomechanical analyses could be oriented for diagnosis and therapy optimization. In this context, there is a great need for the development of accurate tissue constitutive models accounting for highly nonlinear and time-depending effects, governed by different physics and involving mechanisms at different length scales. To this aim, multiscale and multiphysics methods are giving to-date the most promising results (e.g., [6-12]). Accordingly, advanced single-scale and single-physics models of typical tissue substructures, inter-scale and interphysics consistent relationships supported by experimental evidences, homogenization approaches, refined numerical methods and applications, can contribute towards the definition of accurate predictive theories and advanced computational formulations for tissue biomechanics. The Minisymposium aims to bring together front-line researchers in the field of Computational Methods in Tissue Biomechanics, proposing multidisciplinary, original and

Influence of Specimen-Specific Trabecular Anisotropy on QCT-Based Finite Element Analyses of Lumbar Vertebra

Quantitative computed tomography (QCT)-based finite element (FE) models provide better predictions of vertebral strength compared to traditional methods currently used in clinical diagnosis [1]. In QCT-based FE models, the intra- and inter-specimen variations in trabecular anisotropy are often ignored, despite evidence that the biomechanical behavior of the vertebra depends on the architecture of the vertebral trabecular bone [2]. A realistic representation of the specimen-specific, trabecular anisotropy in the FE models of vertebrae would potentially improve predictions of vertebral failure. The overall goal of this study was to evaluate the importance of incorporating specimen-specific, trabecular anisotropy for QCT-based FE predictions of vertebral stiffness and deformation patterns. The major aims of this study were (a) to compare the QCT-based FE results obtained with a constant, anisotropic, material model (the “generic-anisotropic” model) for trabecular bone to those obtained with a specimen-specific, anisotropic, material model and (b) to study the influence of degree of anisotropy (DA) on the FE predictions of vertebral stiffness.Copyright