2,067 research outputs found
Effects of concussive impact injury assessed in a new murine neurotrauma model
Postmortem brains from young athletes with a history of repetitive concussive head injury and military service personnel with history of blast neurotrauma revealed evidence of parenchymal contusion, myelinated axonopathy, microvasculopathy, neuroinflammation, neurodegeneration, and phosphorylated tauopathy consistent with chronic traumatic encephalopathy (CTE) (L. E. Goldstein et al., 2012). The mechanisms by which head trauma induces acute concussion and chronic sequelae are unknown. To elucidate the mechanistic connection between traumatic brain injury (TBI), acute concussion and chronic sequelae, including CTE, require the use of animal models. This doctoral dissertation investigated the hypothesis that closed-head impact injury in mice triggers acute neurological signs associated with sport-related concussion as well as brain pathologies and functional sequelae associated with CTE.
To test this hypothesis, we developed a mouse model of impact neurotrauma that utilizes a momentum transfer device to induce non-skull deforming head acceleration, triggering transient neurological signs consistent with acute concussion and traumatic brain injury (TBI) in unanesthetized C57BL/6 mice. The Boston University Concussion Scale (BUCS) was developed to assess neurological signs that are consistent with acute concussion in humans. Mice exhibited contralateral circling and limb weakness, locomotor abnormalities, and impaired gait and balance that recapitulate acute concussion in humans. Concussed mice recovered neurological function within three hours, but demonstrated persistent myelinated axonopathy, microvasculopathy, neuroinflammation, and phosphorylated tauopathy consistent with early CTE. Concussive impact injury also induced blood-brain barrier disruption, neuroinflammation (including infiltration peripheral monocytes and activation microglia), impaired hippocampal axonal conduction, and defective long-term potentiation (LTP) of synaptic transmission in medial prefrontal cortex. Kinematic analysis during impact injury revealed head acceleration of sufficient intensity to induce acute concussion, traumatic brain injury (TBI), early CTE-linked pathology, and related chronic sequelae.
Surprisingly, the presence or degree of concussion measured by BUCS did not correlate with brain injury. Moreover, concussion was observed following impact injury but not blast exposure under conditions that induce comparable head kinematics. Empirical pressure measurements and dynamic modeling revealed greater pressure on the head and compression wave loading in the brain during impact compared to blast neurotrauma. These findings suggest acute concussion is triggered by focal loading of energy that transit the brain before onset of macroscopic head motion. By contrast, the forces associated with rapid head motion is sufficient to induce CTE-linked pathology. Our results indicate that while acute concussion and chronic sequelae may be triggered by the same insult, the pathophysiological responses underpinning these effects are engaged through distinct mechanisms and time domains. Our results indicate that concussion is neither necessary nor sufficient to induce acute brain injury or chronic sequelae, including CTE.2018-02-17T00:00:00
Desenvolvimento de um modelo computacional do crânio humano
The leading cause of mortality for both children and adults, between the ages
of 5 and 29 years old, is road traffic accidents. To better understand the
mechanisms that cause them or to develop prevention and detection
mechanisms, several finite element models of the human head have been
developed, with the YEAHM developed by members of the university of Aveiro.
For this reason, the purpose of this dissertation is to improve the YEAHM, in
particular the skull, with differentiation between different types of bone tissues,
based on the original external geometry, but segmenting it with sutures, diploë
and cortical bone, and validating it as a tool to predict cranial fractures. Several
validations are performed, comparing the results of the simulation with the
experimental results available in the literature at three levels: i) local validation
of the material; ii) Isolated skull blunt trauma; iii) Coupled cranio-intracranial
structures subjected to three impacts at different speeds, simulating falls.
Accelerations, impact forces and fracture patterns are used to validate the skull
model.A principal causa de mortalidade de crianças e adultos, entre 5 e 29 anos, são
os acidentes de trânsito. Para melhor compreender os mecanismos que os
causam ou desenvolver mecanismos de prevenção e deteção, foram
desenvolvidos vários modelos de elementos finitos da cabeça humana, como o
YEAHM desenvolvido por membros da Universidade de Aveiro. Por esse
motivo, o objetivo desta dissertação é a melhoria do YEAHM, em particular o
crânio, com diferenciação entre diferentes tipos de tecidos ósseos, com base
na geometria externa original, mas segmentando-a com suturas, diploë e osso
cortical, e validá-lo como ferramenta para prever fraturas cranianas. Diversas
validações são realizadas, comparando os resultados da simulação com os
resultados experimentais disponÃveis na literatura em três nÃveis: i) validação
local do material; ii) Lesão contusa isolada do crânio; iii) Estruturas crânio-intracranianas acopladas submetidas a três impactos em diferentes
velocidades, simulando quedas. Acelerações, forças de impacto e padrões de
fratura são usados para validar o modelo do crânio.Mestrado em Engenharia Mecânic
The development of a soft tissue mimicking hydrogel: Mechanical characterisation and 3D printing
Accurate tissue phantoms are difficult to design due to the complex hyperelastic, viscoelastic and biphasic properties of real soft tissues. The aim of this work is to demonstrate the tissue mimicking ability of a composite hydrogel (CH), constituting of poly(vinyl alcohol) (PVA) and phytagel (PHY), as a soft tissue phantom over a range mechanical properties, for a variety of biomedical and tissue engineering applications. Its compressive stress-strain behaviour, relaxation response, tensile impact stresses and surgical needle-tissue interactions were mapped and characterised with respect to its constituent hydrogel formulation. The mechanical characterisation of biological tissues was also investigated and the results were used as the ground truth for mimicking.
The best mimicking hydrogel compositions were determined by combining the most relevant mechanical properties for each desired application. This thesis demonstrates the use of the tissue mimicking composite hydrogel formulations as tissue phantoms for various surgical procedures, including convection enhanced drug delivery, and traumatic brain injury studies. To expand the applications of the CH, a preliminary biological evaluation of the hydrogel was performed using human dermal fibroblasts. Cell seeded on the collagen-coated composite hydrogel showed good attachment and viability.
Finally, a novel fabrication method with the aim of creating samples that replicate the anisotropic properties of biological tissues was developed. A cryogenic 3D printing method utilising the liquid to solid phase change of the composite hydrogel ink was achieved by rapidly cooling the ink solution below its freezing point. The setup was able to successfully create complex 3D brain mimicking material. The method was validated by showing that the mechanical and microstructural properties of the 3D printed material was well matched to its cast-moulded equivalent. This greatly widens the applications of the CH as a mechanically accurate tool for in-vitro testing and also demonstrates promise for future mechanobiology and tissue engineering studies.Open Acces
Meshfree and Particle Methods in Biomechanics: Prospects and Challenges
The use of meshfree and particle methods in the field of bioengineering and biomechanics has significantly increased. This may be attributed to their unique abilities to overcome most of the inherent limitations of mesh-based methods in dealing with problems involving large deformation and complex geometry that are common in bioengineering and computational biomechanics in particular. This review article is intended to identify, highlight and summarize research works on topics that are of substantial interest in the field of computational biomechanics in which meshfree or particle methods have been employed for analysis, simulation or/and modeling of biological systems such as soft matters, cells, biological soft and hard tissues and organs. We also anticipate that this review will serve as a useful resource and guide to researchers who intend to extend their work into these research areas. This review article includes 333 references
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Bioengineering Analysis of Traumatic Brain Injury
Traumatic brain injury (TBI) is a serious health concern affecting over a million people in the UK. Brain shift and herniation, which are closely related to severe disability or death, are important signs of abnormally elevated intracranial pressure (ICP) or space-occupying intracranial mass after trauma.
This research aims to use medical image computing and biomechanical modelling techniques to characterise the specific deformation field of brain tissues under various TBI scenarios and strengthen the biomechanical understanding across the full spectrum of TBI.
Medical image computing provides the research with a solid clinical grounding. To better interpret the neuro-images, three computational tools have been developed, including a CT preprocessing pipeline, an automatic mid-sagittal plane detector and an automatic brain extractor. Using these tools, a novel concept of midplane shift (MPS) is developed to quantitatively evaluate the brain herniation condition across the mid-sagittal plane. In the meantime, a lesion heatmap is generated to quantify the asymmetric haematoma volumes across the mid-sagittal plane. The MPS heatmaps generated for 33 TBI patients with heterogeneous brain pathologies demonstrate highly similar shift patterns. Together with the lesion heatmap, a brain deformation mechanism has been presented: the brain will not deform randomly in response to trauma, instead, it will only deform in a regulated mechanism so that the deformation is directed and restricted to the soft ventricular region, thanks to the anatomic structures of the head such as the falx. The MPS heatmap, the lesion heatmap, together with the novel CT parameters derived from them, provide a rich abundance of information on intracranial brain herniation, for a more complete overview of TBI from medical images.
Biomechanical modelling, being one of the most important tools in trauma biomechanics, has been used to quantitatively simulate the brain shift and herniation condition caused by various intracranial lesions and increasing ICP. Preliminary finite element models reconstructed from the Virtual Human Project have demonstrated some limitations. To resolve the observed deficiencies, an advanced high-fidelity patient-specific FE brain model is constructed and explicitly assessed to optimise its injury simulation performance with the help of the developed medical image computing tools. During simulation, the patient-specific traumatic injuries have been reconstructed by imposing both the primary lesion and the secondary injury. The primary lesion simulation is achieved mechanically by ``indenting" a rigid lesion surface simulating the shape of the haematoma to the brain model. While the secondary swelling is modelled with a thermal-expansion-based method to simulate the bulging brain. Using this approach, the observed brain herniation can be decomposed into a deformation due to pure mass effect of space-occupying primary lesion and a shift as a result of secondary swelling. The head injuries of six different TBI patients have been reconstructed and simulated using the prescribed method. The realistic case study suggested that the subdural haematoma patients, as compared to the epidural haematoma patients, were exposed to more significant secondary swelling, which agrees well with the historical clinical findings. In addition to the realistic TBI case studies, an idealised traumatic lesion simulation is performed to investigate the role of lesion morphology and the lesion locations of onsets, in brain herniations during TBI. It is suggested by the idealised TBI cases that the brain is more sensitive to lesion that is more concentrated spatially, if lesion volumes and lesion locations were exactly the same. Moreover, in terms of lesion locations, lesions that strikes on the temporal region and the anterior region are more likely to lead to greater brain deformation, if other lesion morphologies were equal and no secondary swelling considered.
Ultimately, the developed tools are expected to help clinicians better understand and predict the brain behaviour after the onset of TBI and during subsequent injury evolution.WD Armstrong Trus
Mild Traumatic Brain Injury: Combined in Silico and in Vitro Studies
Mild traumatic brain injury (TBI) is a significant public health concern worldwide and has attracted significant attention due to high-impact sport as well as improvised explosive devices used in military conflicts. The earliest sign of mild TBI is associated with cognitive, behavioral and physical/somatic changes, which are commonly invisible to existing medical techniques. Thus it is essential to target mechanisms of mild TBI and its associated damage measures for earlier diagnosis/treatment and enhanced protection strategies.
In this work, the mechanism of blast-induced mild TBI was inspected through integrated in silico and in vitro models. A three-dimensional (3D) human head model with anatomical details was reconstructed from high-resolution medical images, and positioned in three different directions with respect to the blast wave. The effects of head orientations as well as cerebral blood vessel network in brain mechanics were investigated. The dynamic responses of the brain were monitored by the maximum principal strain (MPS), shear strain (SS), and intracranial pressure (ICP). The developed numerical model was validated by the shock tube experiment using a surrogate head, i.e., water-filled polycarbonate shell. Results demonstrated that the ICP alternations in the brain was initially dominated by the direct blast wave propagation and the skull flexure took effect at a later time. It is worth noting that cerebral blood vessel network induced larger MPS and SS in the brain, which were influenced by vessel diameter and density. Moreover, the contour of the head and its orientation significantly altered the flow dynamics around the head, resulting in different spatial and temporal distributions of brain mechanics. Excessive mechanical stain sensed by brain cells, especially abundant cortical astrocytes, could be a potential index factor for the brain injury.
An in vitro injury model for primary cortical astrocytes was developed to identify the injury threshold. Rat cortical astrocytes cultured on silicone membrane were subjected to equibiaxial pulse stretch. The blast pressure profile on the membrane was monitored and the membrane deformations were captured through the high-speed imaging system. The simulated membrane strain, validated by experimental measures, was used to construct an exposure-response curve. It was observed that live cells declined sharply in the strain range from 18% to 35%, which was identified as the injury threshold of cortical astrocytes.
The obtained damage threshold of rat cortical astrocytes could be inferred about the level of brain injury in a rat. A 3D rat head model was constructed with an impactor mimicking the loading conditions of contact sports. Results revealed that impact depth and impactor shape were the two leading factors affecting brain dynamics. The influence of impactor diameter was region-specific and an increase in impactor diameter could substantially increase brain strains in the region which located directly beneath the impactor. The lateral impact could induce higher strains in the brain than the central impact. Results suggested that indentation depth instead of impact depth would be appropriate to characterize the influence of a softer impactor.
Advisor: Linxia G
Mechanics of Biomaterials
The mechanical behavior of biomedical materials and biological tissues are important for their proper function. This holds true, not only for biomaterials and tissues whose main function is structural such as skeletal tissues and their synthetic substitutes, but also for other tissues and biomaterials. Moreover, there is an intimate relationship between mechanics and biology at different spatial and temporal scales. It is therefore important to study the mechanical behavior of both synthetic and livingbiomaterials. This Special Issue aims to serve as a forum for communicating the latest findings and trends in the study of the mechanical behavior of biomedical materials
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