This study presents a multi-domain computational framework to investigate the long-term performance of permanent and bioabsorbable magnesium fixation devices in orthopaedic fracture applications. The framework integrates a coupled model for bone fracture healing and remodeling, with an enhanced surface-based corrosion model to predict the performance of bioabsorbable magnesium devices. It was found that plated fracture fixation enabled fracture healing outcomes compare to non-plated models by facilitating direct fracture healing. During the fracture healing phase, it was found that the stiff titanium plate provided a better healing response compared to the less stiff bioabsorbable magnesium plates. However, in the longer-term remodeling phase, the titanium plate showed evidence of stress-shielding and inhibited bone remodeling. On the other hand, the magnesium plates showed that there was continued remodeling, which meant that the bone tissue gradually returned to the pre-fracture stress state. While the corrosion rate and pit severity heavily influenced the mechanical support provided by the corroding magnesium fixator, the results showed that fixation was only required to provide mechanical stability to the fracture region for approximately the first 30 days for successful fracture union to occur. This coupled computational framework provides a platform to investigate the role of a wide range of magnesium fixation devices and their design and optimisation in orthopaedic applications.

This paper presents a methodology to establish a process-structure-property (PSP) relationship for the additive manufacturing (AM) of small AISI 316L parts, as might be used in coronary stent applications. The methodology includes a physically based process-structure model based on cellular automata (CA) for microstructure characterization and generation, coupled with crystal plasticity finite element (CPFE) structure-property modelling to predict the mechanical response of the AM part under tensile loading. The effect of AM process variables, such as laser power and scanning speed, are reflected in the PSP modelling through the thermal modelling of AM feeding into the CA model. The CA method is shown to be able to capture microstructure texture, which is key to anisotropic behavior of AM parts. The present study aims to (i) establish a practical link between CA and CPFE models and (ii) identify optimal process variables with respect to ductility.

This study presents a computational framework that investigates the effect of localised surface-based corrosion on the mechanical performance of a magnesium-based alloy. A finite element-based phenomenological corrosion model was used to generate a wide range of corrosion profiles, with subsequent uniaxial tensile test simulations to predict the mechanical response to failure. The python-based detection framework PitScan provides detailed quantification of the spatial phenomenological features of corrosion, including a full geometric tracking of corroding surface. Through this approach, this study is the first to quantitatively demonstrate that a surface -based non-uniform corrosion model can capture both the geometrical and mechanical features of a magnesium alloy undergoing corrosion by comparing to experimental data. Using this verified corrosion modelling approach, a wide range of corrosion scenarios was evaluated and enabled quantitative relationships to be established between the mechanical integrity and key phenomenological corrosion features. In particular, we demonstrated that the minimal cross-sectional area parameter was the strongest predictor of the remaining mechanical strength (R-2 = 0.98), with this relationship being independent of the severity or spatial features of localised surface corrosion. Interestingly, our analysis demonstrated that parameters described in ASTM G46-94 showed weaker correlations to the mechanical integrity of corroding specimens, compared to parameters determined by Pitscan. This study establishes new mechanistic insight into the performance of the magnesium-based materials undergoing corrosion.

This study developed an enhanced phenomenological model for the predictions of surface-based localised corrosion of magnesium alloys for use in medical applications. The modelling framework extended previous surface-based approaches by considering the role of β-phase components throughout the material volume to better predict spatial and temporal aspects of surface-based corrosion in magnesium alloys. This enhanced surface-based corrosion model offers many advantages as it (i) captures multi-directional pitting, (ii) captures various pit morphologies, (iii) eliminates mesh sizing effects, (iv) reduces computational cost through custom time controls (v) offers control of pit sizing and (vi) produces corrosion rates that are independent of pitting parameter values. The model was fully implemented in three dimensions within the finite element framework and shows excellent potential to enable robust predictions of the long-term performance of magnesium-based implants undergoing corrosion.

BACKGROUND:Thoracoabdominal aortic aneurysms (TAAAs) are a life-threatening condition which remain difficult to treat. Endovascular and open surgical repair (OSR) provide treatment options for patients, however, due to the lack of clinical trials comparing these, the optimum treatment option is unknown. OBJECTIVES:To assess the effectiveness and safety of endovascular repair versus conventional OSR for the treatment of TAAAs. SEARCH METHODS:The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 26 April 2021. We also searched references of relevant articles retrieved from the electronic search for additional citations. SELECTION CRITERIA:We considered all published and unpublished randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing endovascular repair to OSR for TAAAs for inclusion in the review. The main outcomes of interest were prevention of aneurysm rupture (participants without aneurysm rupture up to 5 years from intervention), aneurysm-related mortality (30 days and 12 months), all-cause mortality, spinal cord ischaemia (paraplegia, paraparesis), visceral arterial branch compromise causing mesenteric ischaemia or renal failure, and rate of reintervention. DATA COLLECTION AND ANALYSIS:Two review authors independently screened all titles and abstracts identified from the searches to identify those that met the inclusion criteria. We planned to undertake data collection, risk of bias assessment, and analysis in accordance with Cochrane recommendations. We planned to assess the certainty of the evidence using GRADE. MAIN RESULTS:No RCTs or CCTs met the inclusion criteria for this review. AUTHORS' CONCLUSIONS:Due to the lack of RCTs or CCTs, we were unable to determine the safety and effectiveness of endovascular compared to OSR in patients with TAAAs and are unable to provide any evidence on the optimal surgical intervention for this cohort of patients. High-quality RCTs or CCTs addressing this objective are necessary, however conducting such studies will be logistically and ethically challenging for this life-threatening disease.

Issues with current treatments for osteochondral defects such as mosaicplasty and autologous chondrocyte implantation (ACI) are lack of donor material, problems associated with donor sites, necessity of second surgical intervention and cell expansion, difficult site preparation and implant fitting to match the surrounding tissue. This study presents the development of a patient specific implant system for focal osteochondral defects that addresses these issues. Using computer aided design and manufacturing techniques, computed tomography scans are utilized to design the implant and templates that facilitate site preparation to allow for precise and easy implantation of the designed perfectly fitting tissue replacement. Functionality of the system and accurate restoration of a defect is demonstrated by digital before/after comparison and with a prototype. With the presented implantation system larger defects in curved joint surfaces can be restored to an optimal shape in an easier procedure than for instance mosaicplasty. The proposed system potentially allows for later replacement of worn implants.

Biomaterials constructed exclusively of sintered microspheres have great potential in tissue engineering scaffold applications, offering the ability to create shape-specific scaffolds with precise controlled release yet to be matched by traditional additive manufacturing methods. The problem is that these microsphere-based scaffolds are limited in their stiffness for applications such as bone regeneration. Our vision to solve this problem was borne from a hierarchical structure perspective, focusing on the individual unit of the structure: the microsphere itself. In a core-shell approach, we envisioned a stiff core to create a stiff microsphere unit, with a polymeric shell that would enable sintering to the other microsphere units. Therefore, the current study provided a comparison of macroscopic biomaterials built on either polymer microspheres or polymer-coated hard glass microspheres. Identical polycaprolactone (PCL) polymer solutions were used to fabricate microspheres and as a thin coating on soda lime glass microspheres (hard phase). The materials were characterized as loose particles and as scaffolds via scanning electron microscopy, thermogravimetry, differential scanning calorimetry, Raman spectroscopy, mechanical testing, and a live/dead analysis with human umbilical cord-derived Wharton's jelly cells. The elastic modulus of the scaffolds with the thinly coated hard phase was about five times higher with glass microspheres (up to about 25 MPa) than pure polymer microspheres, while retaining the structure, cell adhesion, and chemical properties of the PCL polymer. This proof-of-concept study demonstrated the ability to achieve at least a five-fold increase in macroscopic stiffness via altering the core microsphere units with a core-shell approach.

BACKGROUND:Type B aortic dissection can lead to serious and life-threatening complications such as aortic rupture, stroke, renal failure, and paraplegia, all of which require intervention. Traditionally, these complications have been treated with open surgery. Recently however, endovascular repair has been proposed as an alternative. OBJECTIVES:To assess the effectiveness and safety of thoracic aortic endovascular repair versus open surgical repair for treatment of complicated chronic Type B aortic dissection (CBAD). SEARCH METHODS:The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, and AMED databases, as well as the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers, to 2 August 2021. We searched references of relevant articles retrieved through the electronic search for additional citations. SELECTION CRITERIA:We considered all randomised controlled trials (RCTs) and controlled clinical trials (CCTs) assessing the effects of thoracic aortic endovascular repair (TEVAR) versus open surgical repair (OSR) for treatment of complicated chronic Type B aortic dissection (CBAD). Outcomes of interest were mortality (all-cause, dissection-related), neurological sequelae (stroke, spinal cord ischaemia/paresis-paralysis, vertebral insufficiency), morphological outcomes (false lumen thrombosis, progression of dissection, aortic diameters), acute renal failure, ischaemic symptoms (visceral ischaemia, limb ischaemia), re-intervention, and health-related quality of life. DATA COLLECTION AND ANALYSIS:Two review authors independently screened all titles and abstracts identified by the searches to identify those that met the inclusion criteria. From title and abstract screening, we did not identify any trials (RCTs or CCTs) that required full-text assessment. We planned to undertake data collection and analysis in accordance with recommendations described in the Cochrane Handbook for Systematic Reviews of Interventions. We planned to assess the certainty of evidence using GRADE. MAIN RESULTS:We did not identify any trials (RCTs or CCTs) that met the inclusion criteria for this review. AUTHORS' CONCLUSIONS:Due to lack of RCTs or CCTs investigating the effectiveness and safety of TEVAR compared to OSR for patients with complicated CBAD, we are unable to provide any evidence to inform decision-making on the optimal intervention for these patients. High-quality RCTs or CCTs addressing this objective are necessary. However, conducting such studies will be challenging for this life-threatening disease.

Advancement of subject-specific in-silico medicine requires new imaging protocols tailored to specific anatomical features, paired with new constitutive model development based on structure/function relationships. In this study we develop a new dual-VENC 4D Flow MRI protocol that provides unprecedented spatial and temporal resolution of in-vivo aortic deformation. All previous dual-VENC 4D Flow MRI studies in the literature focus on an isolated segment of the aorta, which fail to capture the full spectrum of aortic heterogeneity that exists along the vessel length. The imaging protocol developed provides high sensitivity to all blood flow velocities throughout the entire cardiac cycle, overcoming the challenge of accurately measuring the highly unsteady non-uniform flow field in the aorta. Cross sectional area change, volumetric flow rate, and compliance are observed to decrease with distance from the heart, while pulse wave velocity is observed to increase. A non-linear aortic lumen pressure-area relationship is observed throughout the aorta, such that a high vessel compliance occurs during diastole, and a low vessel compliance occurs during systole. This suggests that a single value of compliance may not accurately represent vessel behaviour during a cardiac cycle in-vivo. This high-resolution MRI data provides key information on the spatial variation in non-linear aortic compliance which can significantly advance the state-of-the-art of in-silico diagnostic techniques for the human aorta.

An enhanced understanding of the structure and mechanical behavior of atherosclerotic plaque can potentially provide key guidance for clinical intervention and vascular device design. This study presents an investigation of morphological and mechanical properties of iliofemoral (n = 8) and carotid (n = 22) atherosclerotic plaque constituents. μCT analysis is used characterize the content and morphology of calcifications in excised plaques. Calcified particles contribute a significant proportion of the average plaque volume (7.6% carotid; 19.1% iliofemoral), and on average over 50% of this volume (53.7 ± 18.6% carotid; 61.7 ± 15% iliofemoral) is accounted for by the largest individual particle found in the plaque. Fibrous tissue and calcifications were isolated for mechanical testing. Unconfined compression testing of isolated calcifications uncovered viscoelastic behavior. Tensile stress relaxation uncovered viscoelastic behavior in fibrous atherosclerotic samples. Iliofemoral fibrous samples were found to be statistically significantly stiffer (*p < 0.05) than carotid fibrous samples. Results show isolated calcifications are approximately two orders of magnitude stiffer than non-calcified fibrous tissue. The results from this study advance the current understanding of plaque mechanics and suggest that computational simulation of angioplasty procedures should incorporate a discrete representation of atherosclerotic plaque constituents.

This paper, the second of two parts, presents a novel subject-specific in-silico framework in which we uncover the relationship between the spatially varying constituents of the aorta and the non-linear compliance of the vessel during the cardiac cycle uncovered in Part I. In Part II a novel microstructurally motivated constitutive model is developed, and simulations reveal that internal vessel contractility, due to pre-stretched elastin and actively generated smooth muscle stress, must be incorporated, along with collagen strain stiffening, in order to accurately predict the non-linear pressure-area relationship observed in-vivo. Modelling of elastin and smooth muscle contractility allows for the identification of the reference vessel configuration at zero-lumen pressure, in addition to accurately predicting high- and low-compliance regimes under a physiological range of pressures. This modelling approach is also shown to capture the key features of elastin and SMC knockout experiments. The volume fractions of the constituent components of the aortic material model were computed so that the in-silico pressure-area curves accurately predict the corresponding MRI data at each location. Simulations reveal that collagen and smooth muscle volume fractions increase distally, while elastin volume fraction decreases distally, consistent with reported histological data. Furthermore, the strain at which collagen transitions from low to high stiffness is lower in the abdominal aorta, again supporting the histological finding that collagen waviness is lower in this distally. The analyses presented in this paper provides new insights into the heterogeneous structure-function relationship that underlies aortic biomechanics. This novel subject-specific MRI/FEA methodology provides a foundation for personalised in-silico clinical analysis and tailored aortic device development.

Advancement of subject-specific in silico medicine requires new imaging protocols tailored to specific anatomical features, paired with new constitutive model development based on structure/function relationships. In this study, we develop a new dual-velocity encoding coefficient (VENC) 4D flow MRI protocol that provides unprecedented spatial and temporal resolution of in vivo aortic deformation. All previous dual-VENC 4D flow MRI studies in the literature focus on an isolated segment of the aorta, which fail to capture the full spectrum of aortic heterogeneity that exists along the vessel length. The imaging protocol developed provides high sensitivity to all blood flow velocities throughout the entire cardiac cycle, overcoming the challenge of accurately measuring the highly unsteady nonuniform flow field in the aorta. Cross-sectional area change, volumetric flow rate, and compliance are observed to decrease with distance from the heart, while pulse wave velocity (PWV) is observed to increase. A nonlinear aortic lumen pressure-area relationship is observed throughout the aorta such that a high vessel compliance occurs during diastole, and a low vessel compliance occurs during systole. This suggests that a single value of compliance may not accurately represent vessel behavior during a cardiac cycle in vivo. This high-resolution MRI data provide key information on the spatial variation in nonlinear aortic compliance, which can significantly advance the state-of-the-art of in-silico diagnostic techniques for the human aorta.

Significant research has been conducted in the area of coronary stents/scaffolds made from resorbable metallic and polymeric biomaterials. These next-generation bioabsorbable stents have the potential to completely revolutionise the treatment of coronary artery disease. The primary advantage of resorbable devices over permanent stents is their temporary presence which, from a theoretical point of view, means only a healed coronary artery will be left behind following degradation of the stent potentially eliminating long-term clinical problems associated with permanent stents. The healing of the artery following coronary stent/scaffold implantation is crucial for the long-term safety of these devices. Computational modelling can be used to evaluate the performance of complex stent devices in silico and assist in the design and development and understanding of the next-generation resorbable stents. What is lacking in computational modelling literature is the representation of the active response of the arterial tissue in the weeks and months following stent implantation, ie, neointimal remodelling, in particular for the case of biodegradable stents. In this paper, a computational modelling framework is developed, which accounts for two major physiological stimuli responsible for neointimal remodelling and combined with a magnesium corrosion model that is capable of simulating localised pitting (realistic) stent corrosion. The framework is used to simulate different neointimal growth patterns and to explore the effects the neointimal remodelling has on the mechanical performance (scaffolding support) of the bioabsorbable magnesium stent.

For many years, computational modelling and simulation studies have been used by developers to advance device design and have been reported in regulatory medical device submissions. However, cardiovascular stent materials in such computational models are typically assumed to behave as a continuum. This approach assumes that bulk material properties apply to the micro-sized structure, i.e. material behavior is scale independent. However, as size is reduced, mechanical size effects arise as the grain size to specimen width ratio drops below a critical value. These size effects cause material behavior to deviate significantly from bulk material behavior. If such a deviation in material behavior is to be captured within computational models, it is necessary to represent the crystalline structure of a metal and to capture the anisotropic behavior of individual grains within these models. This paper describes the development of such a modelling methodology to investigate the phenomenon of strain localization within grains of a 316L stainless steel specimen under fatigue loading conditions. Copyright © VBRI Press.

Die Symptome von schweren Atemwegsstenosen können durch die Implantation von Stents gelindert werden. Unterschiedliche Atemwegsstents sind kommerziell erhältlich, zumeist werden beschichtete Metallstents oder Stents aus Silikon verwendet. Die bisherigen Stents tragen allerdings Risiken wie Migration oder die Bildung von erneuten Stenosen durch Granulationsgewebe. Über den Zusammenhang von mechanischen Eigenschaften der Stents und Gewebereaktion nach Implantation gibt es bislang kaum Daten.

For many years, computational modelling and simulation studies have been used by developers to advance device design and have been reported in regulatory medical device submissions. However, cardiovascular stent materials in such computational models are typically assumed to behave as a continuum. This approach assumes that bulk material properties apply to the micro-sized structure, i.e. material behavior is scale independent. However, as size is reduced, mechanical size effects arise as the grain size to specimen width ratio drops below a critical value. These size effects cause material behavior to deviate significantly from bulk material behavior. If such a deviation in material behavior is to be captured within computational models, it is necessary to represent the crystalline structure of a metal and to capture the anisotropic behavior of individual grains within these models. This paper describes the development of such a modelling methodology to investigate the phenomenon of strain localization within grains of a 316L stainless steel specimen under fatigue loading conditions.

Regional variance in human aortic bioarchitecture responsible for the elasticity of the vessel is poorly understood. The current study quantifies the elements responsible for aortic compliance, namely, elastin, collagen and smooth muscle cells, using histological and stereological techniques on human tissue with a focus on regional heterogeneity. Using donated cadaveric tissue, a series of samples were excised between the proximal ascending aorta and the distal abdominal aorta, for five cadavers, each of which underwent various staining procedures to enhance specific constituents of the wall. Using polarised light microscopy techniques, the orientation of collagen fibres was studied for each location and each tunical layer of the aorta. Significant transmural and longitudinal heterogeneity in collagen fibre orientations were uncovered throughout the vessel. It is shown that a von Mises mixture model is required accurately to fit the complex collagen fibre distributions that exist along the aorta. Additionally, collagen and smooth muscle cell density was observed to increase with increasing distance from the heart, whereas elastin density decreased. Evidence clearly demonstrates that the aorta is a highly heterogeneous vessel which cannot be simplistically represented by a single compliance value. The quantification and fitting of the regional aortic bioarchitectural data, although not without its limitations, including mean cohort age of 77.6 years, facilitates the development of next-generation finite element models that can potentially simulate the influence of regional aortic composition and microstructure on vessel biomechanics.

The aim was to investigate mechanical and functional failure of diffuse axonal injury (DAI) in nerve bundles following frontal head impacts, by finite element simulations. Anatomical changes following traumatic brain injury are simulated at the macroscale by using a 3D head model. Frontal head impacts at speeds of 2.5-7.5 m/s induce mild-to-moderate DAI in the white matter of the brain. Investigation of the changes in induced electromechanical responses at the cellular level is carried out in two scaled nerve bundle models, one with myelinated nerve fibres, the other with unmyelinated nerve fibres. DAI occurrence is simulated by using a real-time fully coupled electromechanical framework, which combines a modulated threshold for spiking activation and independent alteration of the electrical properties for each three-layer fibre in the nerve bundle models. The magnitudes of simulated strains in the white matter of the brain model are used to determine the displacement boundary conditions in elongation simulations using the 3D nerve bundle models. At high impact speed, mechanical failure occurs at lower strain values in large unmyelinated bundles than in myelinated bundles or small unmyelinated bundles; signal propagation continues in large myelinated bundles during and after loading, although there is a large shift in baseline voltage during loading; a linear relationship is observed between the generated plastic strain in the nerve bundle models and the impact speed and nominal strains of the head model. The myelin layer protects the fibre from mechanical damage, preserving its functionalities.