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Currently, the approach most widely used to examine bone loss is the measurement of bone mineral density (BMD) using dual X-ray absorptiometry (DXA). However, bone loss due to immobilization creates changes in bone microarchitecture, which in turn are related to changes in bone mechanical function and competence to resist fracture. Unfortunately, the relationship between microarchitecture and mechanical function within the framework of immobilization and antiresorptive therapy has not being fully investigated. The goal of the present study was to investigate the structure–function relationship in trabecular bone in the real-world situations of a rapidly evolving osteoporosis (disuse), both with and without antiresorptive treatment. We evaluated the structure–function relationship in trabecular bone after bone loss (disuse-induced osteoporosis) and bisphosphonate treatment (antiresorptive therapy using risedronate) in canine trabecular bone using μCT and ultrasound wave propagation. Microstructure values determined from μCT images were used into the anisotropic poroelastic model of wave propagation in order to compute the apparent elastic constants (EC) and elastic anisotropy pattern of bone. Immobilization resulted in a significant reduction in trabecular thickness (Tb.Th) and bone volume fraction (BV/TV), while risedronate treatment combined with immobilization exhibited a lesser reduction in Tb.Th and BV/TV, suggesting that risedronate treatment decelerates bone loss, but it was unable to fully stop it. Risedronate treatment also increased the tissue mineral density (TMD), which when combined with the decrease in Tb.Th and BV/TV may explain the lack of significant differences in vBMD in both immobilization and risedronate treated groups. Interestingly, changes in apparent EC were much stronger in the superior–inferior (SI) direction than in the medial–lateral (ML) and anterior–posterior (AP) anatomical directions, producing changes in elastic anisotropy patterns. When data were pooled together, vBMD was able to explain 58% of ultrasound measurements variability, a poroelastic wave propagation analytical model (i.e., BMD modulated by fabric directionality) was able to predict 81% of experimental wave velocity variability, and also explained 91% of apparent EC and changes in elastic anisotropy patterns. Overall, measurements of vBMD were unable to distinguish changes in apparent EC due to immobilization or risedronate treatment. However, anisotropic poroelastic ultrasound (PEUS) wave propagation was able to distinguish functional changes in apparent EC and elastic anisotropy patterns due to immobilization and antiresorptive therapy, providing an enhanced discrimination of anisotropic bone loss and the structure–function relationship in immobilized and risedronate-treated bone, beyond vBMD.

Currently, aortic valve replacement procedures require a sternotomy and use of cardiopulmonary bypass (CPB) to arrest the heart and provide a bloodless field in which to operate. A less invasive alternative to open heart surgery is transapical or transcatheter aortic valve replacement (TAVR), already emerging as a feasible treatment for patients with high surgical risk. The bioprosthetic valves are delivered via catheters using transarterial or transapical approaches and are implanted within diseased aortic valves. This paper reports the development of a new self-expanding stent for minimally invasive aortic valve replacement and its delivery device for the transapical approach under real-time magnetic resonance imaging (MRI) guidance. Made of nitinol, the new stent is designed to implant and embed a commercially available bioprosthetic aortic valve in aortic root. An MRI passive marker was affixed onto the stent and an MRI active marker to the delivery device. These capabilities were tested in ex vivo and in vivo experiments. Radial resistive force, chronic outward force, and the integrity of bioprosthesis on stent were measured through custom design dedicated test equipment. In vivo experimental evaluation was done using a porcine large animal model. Both ex vivo and in vivo experiment results indicate that the self-expanding stent provides adequate reinforcement of the bioprosthetic aortic valve and it is easier to implant the valve in the correct position. The orientation and positioning of the implanted valve is more precise and predictable with the help of the passive marker on stent and the active marker on delivery device. The new self-expanding nitinol stent was designed to exert a constant radial force and, therefore, a better fixation of the prosthesis in the aorta, which would result in better preservation of long-term heart function. The passive marker affixed on the stent and active marker embedded in the delivery devices helps to achieve precise orientation and positioning of the stent under MRI guidance. The design allows the stent to be retracted in the delivery device with a snaring catheter if necessary. Histopathology reports reveal that the stent is biocompatible and fully functional. All the stented bioprosthesis appeared to be properly seated in the aortic root.

Margarine as a raw material has a multiple uses in the production of bio-organic materials such as refined oil and butter. It passes through many industrial stages before beginning the process of refining and packaging it to the consumer. One of these important stages is the melting process, which wastes an immense amount of thermal power. The large rate of thermal power consumption occurs due to the huge reservoirs in which the margarine is stored (500 m3–1500 m3 Savola International Company-Suez Gulf region-Egypt). With drawing margarine from the reservoirs is a cost and time intensive process due to the solid state of margarine at environmental temperatures. Dry saturated steam is passed through the heat exchanger pipes inside the reservoir to melt the required amount of margarine. In some cases, this process can take up to 8 h in the summer and 12 h in the winter, which can be amplified by the loss of heat energy from the reservoir throughout the day, especially during the night periods. Moreover, steam boilers that use heavy fuel or natural gas can cause serious environmental damage as a result of emissions, such as the carbon oxide and nitrous oxide compounds. In contrast, solar energy is one of the cleanest and environmentally friendly renewable energies and should be invested as an alternative heat source for the melting process of margarine. As mentioned before, the melting of margarine is considered a heating process that consumes a huge amount of thermal energy. Therefore, solar thermal power can play a vital role in the process of melting margarine. Generally, temperature requirements of solar industrial heat applications range from 60 °C to 260 °C. Cylindrical PTC systems look very promising for delivering industrial heating process applications in the range of 95 °C–350 °C delivery temperature [1]. For solar thermal applications, the operating design conditions of solar collectors should be well above the desired operating conditions of the application to ensure stability of the operation. Therefore, flat plate collectors and evacuated tube collectors are eliminated from this study due to the previous reason and its lower efficiencies compared against the PTC [2]. This is why medium to medium–high temperature solar collectors are used [3,4]. Most of the production processes of the food industry such as milk products, vegetable, meat, fruits, and beer are run at temperatures below or near 100–130 °C. In addition, many cleaning processes such as pasteurizing, sterilizing, drying, hydrolyzing, distillation, washing, polymerization, and cooking processes are conducted under thermal applications [5,6]. Thus, switching to a renewable energy source, such as solar energy, can result in cost savings as well as decrease the negative impacts the production process has on the environment. The production process of margarine requires a large amount of heat in which solar thermal power is a viable and more cost effective source of energy. The problem originally emerged when Savola's company officials (Savola International Company in Margarine industrial Suez Gulf region-Egypt) decided to optimize the time, energy, and cost of the production process. They summarized their problems into the following points: The process of margarine melts takes more than 12 h to obtain 100–200 m3 of melted margarine per day. Which costs the equivalent amount of 476,120 m3 per day of natural gas (100,000 $/month). Reduction of CO2, NO2, and CO emissions is a must according to environmental laws. After reviewing the configuration of their heating process, using solar thermal power as a clean energy alternative seemed to be the most viable solution. Egypt has a great potential for solar energy. It is calculated that an amount of 6–7 kW h/m2/day of global radiation is in the Suez Gulf region-Egypt [8]. Therefore, it is very promising to utilize this vast amount of untapped solar energy in this industrial heating process. The aim of this research is to present a feasibility study, assessing the impact of using solar thermal power as an alternative source of energy in the margarine melting process. In this study, solar PTC is used instead of a conventional steam boiler. Water–steam and/or Therminol-VP1 [7] HTO are utilized through the PTC representing two different configurations. The data results of the conventional configuration (config1) are compared with the PTC–water steam configuration (config2) and PTC–Therminol configuration (config3) according to the hourly cost parameter ($/h). The study plan is organized as follows: The process configurations for the proposed systems are performed and the design limits are investigated. The mathematical model that represents the proposed systems is constructed. Three cases are compared (solar direct vapor generation (two configurations) was conventional configuration). Practical and analytical solutions for the process problems are studied and executed. solar desalination system (SDS) software package (a part of renewable energy desalination system (REDS) that were developed by the authors) was used to model all the system units [8–11]. 2. Margarine Melting Heating Process 2.1. The Process Problems. The problem began when Savola's-Egypt officials decided to evaluate the productive performance of their company. In their current configuration, a steam boiler running on fuels is used in the heating process. The company was faced with several problems identified as below. Wasted time, especially in the winter it requires melting about 100–300 m3 within approximately 12 h. This requires a significant amount of time before the canning process can begin. In addition, the steam boiler has to be operated during night hours to collect the melted margarine early in the morning before the canning process. It is noted that the fuel consumption is also very high, especially in the case of heavy fuel operations. As the average daily consumption reached 1 m3 or more, which is considered to be a high rate of consumption. The exhaust emissions resulting from the combustion inside the steam boiler today are unacceptable in the light of international regulations which intend to reduce global carbon emissions. Because of the temperature difference during the night especially in winter a large amount of thermal power gets wasted. This increases the operation time and the rate of fuel consumption. Thus, Savola's Egyptian officials contacted the authors to investigate and propose solutions to the existing inefficiencies, while at the same time decreasing the negative impact on the environment.

Prior to developing any specific fall detection algorithm, it is critical to distinguish the unique motion features associated with fall accidents. The current study aimed to investigate the upper trunk angular kinematics during slip-induced backward falls and activities of daily living (ADLs). Ten healthy older adults (age = 75 ± 6 yr (mean ± SD)) were involved in a laboratory study. Sagittal trunk angular kinematics were measured using optical motion analysis system during normal walking, slip-induced backward falls, lying down, bending over, and various types of sitting down (SN). Trunk angular phase-plane plots were generated to reveal the motion features of falls. It was found that backward falls were characterized by a simultaneous occurrence of a slight trunk extension and an extremely high trunk extension velocity (peak average = 139.7 deg/s), as compared to ADLs (peak average = 84.1 deg/s). It was concluded that the trunk extension angular kinematics of falls were clearly distinguishable from those of ADLs from the perspective of angular phase-plane plot. Such motion features can be utilized in future studies to develop a new prior-to-impact fall detection algorithm.

Mechanical loading and elevated levels of proinflammatory cytokines have been implicated in the risk for premature OA following traumatic knee injuries such as rupture of the anterior cruciate ligament (ACL) or meniscal injury [1–3]. Changes in the in vivo functional joint motion [4–6] alone or in combination with changes in joint biochemistry [7–12] after injury is one potential kinematic pathway to the initiation of post traumatic OA [13,14]. Evidence for the support of a kinematic pathway has been based on evidence of regional topological variations in the properties of knee articular cartilage structure that are thought to arise in response to the variation in local mechanical environment [15]. It has been shown that chondrocyte populations in different regions of the tibial plateau (covered by meniscus versus not covered by meniscus) respond differently to equivalent tissue level mechanical loading [16]. Thus alteration in the in vivo functional joint motion may result in subtle shifts in the load distribution at the knee altering the local mechanical environment and exposing chondrocytes to loading patterns they are unaccustomed to thereby contributing to degenerative changes. While changes in the in vivo function of the joint may alone contribute to degenerative changes in articular cartilage of the knee, changes in joint biochemistry are also likely contributing factors. In the healthy knee, synovial fluid concentrations of proinflammatory cytokines are small [7,8,11] with moderate levels for the protective cytokine interleukin-1 receptor antagonist (IL-1ra) [8]. Following ACL injury the most consistent acute cytokine responses observed are increased levels of IL-6, IL-8, and TNF-α [7,8,10]. Although these levels decrease within weeks of the injury, they are still elevated relative to healthy subjects [7–9,11] and are similar to synovial fluid concentrations observed in patients with OA [10]. One cytokine of interest, TNF-α has the ability to induce chondrocyte-mediated cartilage degradation by elevating production of degradative enzymes [17] and inhibiting synthesis [18–20] and expression [20] of structural proteins, leading to increased matrix degradation [21–23]. In vitro studies [24,25] have demonstrated that the specific effects of certain cytokines may be modulated through mechanical loading. Moderate levels of dynamic compression appear to inhibit some of the catabolic effects of interleukin-1 on articular chondrocytes [24,25]. However, proteoglycan (PG) loss in cartilage explants subjected to injurious compression and cultured in the presence of TNF-α was greater than that produced by either injurious compression or TNF-α treatment alone [26]. The coactive effects of TNF-α and in vitro dynamic compression on chondrocyte gene expression are not well understood, particularly for cartilage from distinct regions of the tibial plateau. Thus, the purpose of this study was to evaluate the regional response of chondrocytes to the coaction of load and biological stimuli by testing the following hypotheses: (1) There are significant differences in the gene expression of chondrocytes to a combined application of dynamic compression with exogenous proinflammatory cytokine (Load + TNF-α) relative to the gene expression in response to isolated Load or TNF-α stimuli. (2) Gene expression in response to Load, TNF-α and Load + TNF-α stimuli will be different in the central and peripheral regions of tibial cartilage.

Tears on the bursal and articular sides of the rotator cuff tendons are known to behave differently and strain is thought to play a role in this difference. This study investigates the effect of tear location on the changes in three strain measurements (grip-to-grip, insertion, and mid-substance tissue) in a sheep infraspinatus tendon model during axial loading. We introduced a 14 mm wide defect near the insertion from either the articular or bursal side of the tendon to three depths (3 mm, 7 mm & full) progressively. For each condition, tendons were sinusoidally stretched (4% at 0.5 Hz) while insertion and mid-substance strains were tracked with surface markers. For a fixed load, grip-to-grip strain increased significantly compared to intact for both cuts. Insertion strain increased significantly for the bursal-side defect immediately but not for the articular-side until the 66% cut. Mid-substance tissue strain showed no significant change for partial thickness articular-side defects and a significant decrease for bursal-side defects after the 66% cut. All full thickness cuts exhibited negligible mid-substance tissue strain change. Our results suggest that the tendon strain patterns are more sensitive to defects on the bursal side, and that partial thickness tears tend to induce localized strain concentrations in regions adjacent to the damaged tissue.

Computational modeling is very useful in biomechanics to simulate normal and pathologic joint function. It is also useful to determine the efficacies of various surgical procedures performed to treat joint pathologies and simulate their outcomes. Models can be used to estimate in situ measures such as contact pressure distributions that are difficult to acquire through experiments noninvasively. Currently, computational modeling is the only technique available to noninvasively evaluate in vivo joint contact mechanics [1]. However, most models make use of input parameters derived from various general sources such as literature, standards, or experiments and are, therefore, limited for patient-specific applications [2]. Joint injuries, whether ligaments or articular surface, are a significant problem and there is still a need for tools to effectively evaluate joint injuries and associated sequelae [3]. The ability to monitor the initiation and progression of joint instability after injury may aid in determining prognosis, leading to better treatment algorithms. In order to refine or develop treatments that are targeted toward individuals, it is important to focus on subject-specific models. Several modeling techniques exist to evaluate in vivo joint mechanics. The common techniques include image-based FEM [4–13], rigid body spring modeling/discrete element analysis (RBSM) [14–16], or SCM [17–19]. The models are either displacement driven or force driven. Generally, model geometries are acquired from modalities such as computed tomography (CT) [4–8,14,15,19] or MRI [9–11,17,18]. Kinematics are determined through external (surface markers) or internal (biplanar radiography) measures, while tendon forces are estimated from corresponding musculature electromyography (EMG) and cross-sectional area, and ground reaction forces are measured using force platforms [11,20]. These loads and displacement boundary conditions are input into the model to infer joint kinetics/kinematics and resulting surface and/or volumetric stresses and strains. FEM is the most common and accurate method to determine stresses [11,20,21]. However, depending on the complexity of the problem, the process of developing the mesh can be laborious and obtaining a converged solution can be computationally intensive [22], which limits its clinical applicability. Depending on the type of problem (for instance, deformable versus rigid), more simplified analyses can be performed based on relevant assumptions to determine appropriate solutions. This is the basis of RBSM and SCM techniques. Using these methods, joint mechanics can be evaluated in a computationally efficient manner compared to FEM [23], which makes them relevant for clinical applications. The underlying question is whether these methods are competent to provide data that are sufficiently accurate for the intended application. The ability to accurately determine joint mechanics has wide clinical implications, especially in complex joints such as the wrist. It may be possible to sufficiently evaluate changes in joint mechanics as a result of injury or surgical intervention from surface contact mechanics data alone. This can be achieved through the SCM technique, without the need for a complex volumetric analysis [24]. However, the SCM technique has not been extensively used for orthopedic applications. Computational modeling has been extensively applied to the lower extremity to evaluate in vivo joint mechanics [4–11,18]. In the wrist, studies have evaluated in vivo joint mechanics during functional activities [12,14,16,17] and have also simulated the effects of some carpal fractures and limited fusions [13,15,19]. Scapholunate (SL) ligament injury is a commonly occurring wrist ligament injury that can lead to SL joint instability and progressive degenerative changes [25–28]. Prior modeling work on the in vivo effects of SL ligament injury or surgical repair appears to be limited [29,30]. Hence, we investigated differences in radiocarpal in vivo joint mechanics obtained from SCM for normal wrists, after SL ligament injury, and after surgical repair to results from the FEM “gold standard.” We did not intend to make comparisons between the normal, injured, and postoperative states. Our goal was to show that contact outcomes obtained from SCM would be comparable to those obtained from a similar FEM analysis regardless of wrist state and to demonstrate the feasibility and applicability of the SCM technique.

The ability to predict patient-specific joint contact and muscle forces accurately could improve the treatment of walking-related disorders. Muscle synergy analysis, which decomposes a large number of muscle electromyographic (EMG) signals into a small number of synergy control signals, could reduce the dimensionality and thus redundancy of the muscle and contact force prediction process. This study investigated whether use of subject-specific synergy controls can improve optimization prediction of knee contact forces during walking. To generate the predictions, we performed mixed dynamic muscle force optimizations (i.e., inverse skeletal dynamics with forward muscle activation and contraction dynamics) using data collected from a subject implanted with a force-measuring knee replacement. Twelve optimization problems (three cases with four subcases each) that minimized the sum of squares of muscle excitations were formulated to investigate how synergy controls affect knee contact force predictions. The three cases were: (1) Calibrate+Match where muscle model parameter values were calibrated and experimental knee contact forces were simultaneously matched, (2) Precalibrate+Predict where experimental knee contact forces were predicted using precalibrated muscle model parameters values from the first case, and (3) Calibrate+Predict where muscle model parameter values were calibrated and experimental knee contact forces were simultaneously predicted, all while matching inverse dynamic loads at the hip, knee, and ankle. The four subcases used either 44 independent controls or five synergy controls with and without EMG shape tracking. For the Calibrate+Match case, all four subcases closely reproduced the measured medial and lateral knee contact forces (R2 ≥ 0.94, root-mean-square (RMS) error < 66 N), indicating sufficient model fidelity for contact force prediction. For the Precalibrate+Predict and Calibrate+Predict cases, synergy controls yielded better contact force predictions (0.61 < R2 < 0.90, 83 N < RMS error < 161 N) than did independent controls (-0.15 < R2 < 0.79, 124 N < RMS error < 343 N) for corresponding subcases. For independent controls, contact force predictions improved when precalibrated model parameter values or EMG shape tracking was used. For synergy controls, contact force predictions were relatively insensitive to how model parameter values were calibrated, while EMG shape tracking made lateral (but not medial) contact force predictions worse. For the subject and optimization cost function analyzed in this study, use of subject-specific synergy controls improved the accuracy of knee contact force predictions, especially for lateral contact force when EMG shape tracking was omitted, and reduced prediction sensitivity to uncertainties in muscle model parameter values.

ATAA are dilatations of the arterial wall that result primarily from a weakening in the middle smooth muscle layer, or media, of the artery [1–3]. Aneurysm dissection and rupture pose serious risk of mortality and are the primary concerns for patients with an ATAA [1–4]. Cystic medial degeneration (which can be caused by disease, injury, or hereditary condition [2,3]), weakens the aortic wall, allowing for the formation of aneurysms and subsequent dissections. Aneurysm growth and dissection is further driven by increased hemodynamic loading within the media [5]. Ascending aortic dissection, the most prominent failure mode, occurs when the hemodynamic stresses within the media exceed the capacity of its collagen and elastin constituents allowing blood to pass into the medial lamella and peel it apart (delaminate) [6]. Ultimately, this tear can propagate axially along the length of the aorta, either proximally or distally, and in the absence of clinical intervention, may lead to further complications such as ischemia, aortic regurgitation, cardiac tamponade, aortic rupture, and death [1]. Ascending aortic aneurysms have an incidence rate of 10.4 per 100,000 person-years [7], with significant risk of dissection or rupture [7]. Clinically, ATAA management balances the risk of aneurysm rupture with the risk of surgery-related complications and death [2,3]. Risk of rupture is correlated with aneurysm diameter [2,7]; aneurysms greater than 6 cm in diameter exhibit a significantly higher risk of rupture [2]. Thus, for patients without valvular disorders, current guidelines indicate surgical intervention for ATAA diameters greater than 5.5 cm and monitoring for those less than 5.5 cm [2]. In spite of clinical guidelines and what is known about the pathogenesis of aneurysms, dissection and rupture occur in a significant number of patients whose aneurysms are less than 5.5 cm in diameter [8], suggesting that a better understanding of the dissection process is needed. Experimental studies have investigated the mechanical failure of aortic media [6,9,10], but only a few theoretical models have attempted to emulate this response [11–13]. The most notable work to date, by Gasser and Holzapfel [12], employs constitutive FE modeling with two independent continuous and cohesive zones to model the fiber network and ground matrix, respectively. While the Gasser–Holzapfel model is capable of describing the mechanical behavior of the aorta, it fails to capture complex fiber-fiber and fiber-matrix interactions or address failure at the microscopic scale. A model employing microscale mechanics and structure to determine the macroscale response would have potential to incorporate greater anatomical detail and could be applied to a broader range of conditions. This work represents an initial attempt to apply such multiscale concepts to the mechanics of the ATA. The objectives of this study were (1) to characterize the prefailure and failure response of healthy porcine ascending aorta tissue under uniaxial and biaxial loading and (2) to describe that response with a multiscale, FE damage model. The model has been shown to be effective for prefailure and failure behavior of collagen gels [14] and has been applied to prefailure behavior of decellularized arterial wall [15].

Angiogenesis is the process by which new blood vessels sprout from existing blood vessels, enabling new vascular elements to be added to an existing vasculature. This review discusses our investigations into the role of cell-matrix mechanics in the mechanical regulation of angiogenesis. The experimental aspects of the research are based on in vitro experiments using an organ culture model of sprouting angiogenesis with the goal of developing new treatments and techniques to either promote or inhibit angiogenic outgrowth, depending on the application. Computational simulations were performed to simulate angiogenic growth coupled to matrix deformation, and live two-photon microscopy was used to obtain insight into the dynamic mechanical interaction between angiogenic neovessels and the extracellular matrix. In these studies, we characterized how angiogenic neovessels remodel the extracellular matrix (ECM) and how properties of the matrix such as density and boundary conditions influence vascular growth and alignment. Angiogenic neovessels extensively deform and remodel the matrix through a combination of applied traction, proteolytic activity, and generation of new cell-matrix adhesions. The angiogenic phenotype within endothelial cells is promoted by ECM deformation and remodeling. Sensitivity analysis using our finite element model of angiogenesis suggests that cell-generated traction during growth is the most important parameter controlling the deformation of the matrix and, therefore, angiogenic growth and remodeling. Live two-photon imaging has also revealed numerous neovessel behaviors during angiogenesis that are poorly understood such as episodic growth/regression, neovessel colocation, and anastomosis. Our research demonstrates that the topology of a resulting vascular network can be manipulated directly by modifying the mechanical interaction between angiogenic neovessels and the matrix.

The remodeling of the cervix from a rigid barrier into a compliant structure, which dilates to allow for delivery, is a critical process for a successful pregnancy. Changes in the mechanical properties of cervical tissue during remodeling are hypothesized to be related to the types of collagen crosslinks within the tissue. To further understand normal and abnormal cervical remodeling, we quantify the material properties and collagen crosslink density of cervical tissue throughout pregnancy from normal wild-type and Anthrax Toxin Receptor 2 knockout (Antxr2-/-) mice. Antxr2-/- females are known to have a parturition defect, in part, due to an excessive accumulation of extracellular matrix proteins in the cervix, particularly collagen. In this study, we determined the mechanical properties in gestation-timed cervical samples by osmotic loading and measured the density of mature collagen crosslink, pyridinoline (PYD), by liquid chromatography tandem mass spectrometry (LC-MSMS). The equilibrium material response of the tissue to loading was investigated using a hyperelastic material model where the stresses in the material are balanced by the osmotic swelling tendencies of the glycosaminoglycans and the tensile restoring forces of a randomly-oriented crosslinked collagen fiber network. This study shows that the swelling response of the cervical tissue increased with decreasing PYD density in normal remodeling. In the Antxr2-/- mice, there was no significant increase in swelling volume or significant decrease in crosslink density with advancing gestation. By comparing the ECM-mechanical response relationships in normal and disrupted parturition mouse models this study shows that a reduction of collagen crosslink density is related to cervical softening and contributes to the cervical remodeling process.

Approximately 7.5 × 106 patients in the US currently suffer from end-stage heart failure. The FDA has recently approved the designations of the Thoratec HeartMate II ventricular assist device (VAD) for both bridge-to-transplant and destination therapy (DT) due to its mechanical durability and improved hemodynamics. However, incidence of pump thrombosis and thromboembolic events remains high, and the life-long complex pharmacological regimens are mandatory in its VAD recipients. We have previously successfully applied our device thrombogenicity emulation (DTE) methodology for optimizing device thromboresistance to the Micromed Debakey VAD, and demonstrated that optimizing device features implicated in exposing blood to elevated shear stresses and exposure times significantly reduces shear-induced platelet activation and significantly improves the device thromboresistance. In the present study, we compared the thrombogenicity of the FDA-approved HeartMate II VAD with the DTE-optimized Debakey VAD (now labeled HeartAssist 5). With quantitative probability density functions of the stress accumulation along large number of platelet trajectories within each device which were extracted from numerical flow simulations in each device, and through measurements of platelet activation rates in recirculation flow loops, we specifically show that: (a) Platelets flowing through the HeartAssist 5 are exposed to significantly lower stress accumulation that lead to platelet activation than the HeartMate II, especially at the impeller-shroud gap regions (b) Thrombus formation patterns observed in the HeartMate II are absent in the HeartAssist 5 (c) Platelet activation rates (PAR) measured in vitro with the VADs mounted in recirculation flow-loops show a 2.5-fold significantly higher PAR value for the HeartMate II. This head to head thrombogenic performance comparative study of the two VADs, one optimized with the DTE methodology and one FDA-approved, demonstrates the efficacy of the DTE methodology for drastically reducing the device thrombogenic potential, validating the need for a robust in silico/in vitro optimization methodology for improving cardiovascular devices thromboresistance.

Type I Chiari malformation (CMI) is a complex disorder of the craniospinal system that has historically been radiologically defined by cerebellar tonsillar herniation (CTH) greater than 3–5 mm below the foramen magnum (FM) into the spinal subarachnoid space (SSS) (Fig. ​(Fig.11 ) [1–3]. Patients with CMI can have a variety of neurological symptoms and pain ranging from mild to severe [1]. It is thought that these symptoms result from abnormal pressure acting on the spinal cord, brain stem, and/or cerebellum due to crowding of the tissue in the posterior cranial fossa and craniovertebral junction (CVJ) [4–6]. However, large retrospective clinical studies have shown that CMI symptom severity does not always correlate with CTH depth [7]. Patients with large CTH may present with mild neurological symptoms and vice versa [6]. Fig. 1 (a) Midsagittal MRI image of the cervical spine of a CMI patient showing the McRae line, CTH measurement (approximately 7.4 mm for this case), and planes where pressure drop was calculated; (b) transverse MRI image from the plane used to demarcate ... As such, clinicians have sought additional objective measurements to assist in the diagnostic process. In clinical practice, the diagnostic process can vary widely; clinicians have differing views on the importance of CTH alongside many factors such as symptom history, neurologic deficit, degree of craniocervical “crowding” bony landmark positions, and cisterna magna volume. CTH greater than 3–5 mm as a marker for CMI has been established as a ‘rule of thumb’ over time. This is problematic, as incidental observation of CTH has become more common with increases in the use of magnetic resonance imaging (MRI) for head and neck injury examinations. Recent research has shown that as much as 3% of the pediatric population, 2% of the adult female population, and 1% of the adult male population have greater than 5 mm CTH [8,9] and CTH varies throughout life (Fig. ​(Fig.22). Fig. 2 CTH as a function of age (in decade range, e.g., first decade 0–10 y) and sex for healthy subjects showing a parabolic trend with females having greater CTH values throughout life. Positive CTH values are in the caudal direction to the ...

Single-walled carbon nanohorns (SWNHs) have significant potential for use in photothermal therapies due to their capability to absorb near infrared light and deposit heat. Additionally, their extensive relative surface area and volume makes them ideal drug delivery vehicles. Novel multimodal treatments are envisioned in which laser excitation can be utilized in combination with chemotherapeutic-SWNH conjugates to thermally enhance the therapeutic efficacy of the transported drug. Although mild hyperthermia (41–43 °C) has been shown to increase cellular uptake of drugs such as cisplatin (CDDP) leading to thermal enhancement, studies on the effects of hyperthermia on cisplatin loaded nanoparticles are currently limited. After using a carbodiimide chemical reaction to attach CDDP to the exterior surface of SWNHs and nitric acid to incorporate CDDP in the interior volume, we determined the effects of mild hyperthermia on the efficacy of the CDDP-SWNH conjugates. Rat bladder transitional carcinoma cells were exposed to free CDDP or one of two CDDP-SWNH conjugates in vitro at 37 °C and 42 °C with the half maximal inhibitory concentration (IC50) for each treatment. The in vitro results demonstrate that unlike free CDDP, CDDP-SWNH conjugates do not exhibit thermal enhancement at 42 °C. An increase in viability of 16% and 7% was measured when cells were exposed at 42 deg compared to 37 deg for the surface attached and volume loaded CDDP-SWNH conjugates, respectively. Flow cytometry and confocal microscopy showed a decreased uptake of CDDP-SWNH conjugates at 42 °C compared to 37 °C, revealing the importance of nanoparticle uptake on the CDDP-SWNH conjugate's efficacy, particularly when hyperthermia is used as an adjuvant, and demonstrates the effect of particle size on uptake during mild hyperthermia. The uptake and drug release studies elucidated the difference in viability seen in the drug efficacy studies at different temperatures. We speculate that the disparity in thermal enhancement efficacy observed for free drug compared to the drug SWNH conjugates is due to their intrinsic size differences and, therefore, their mode of cellular uptake: diffusion or endocytosis. These experiments indicate the importance of tuning properties of nanoparticle-drug conjugates to maximize cellular uptake to ensure thermal enhancement in nanoparticle mediated photothermal-chemotherapy treatments.

The intervertebral disc (IVD) is a heterogeneous, fibrocartilaginous tissue that provides load support, energy dissipation, and flexibility in the spine. The IVD, which is composed of the nucleus pulposus (NP), anulus fibrosus (AF), and cartilage endplate (Fig. ​(Fig.1),1), is situated between adjacent vertebral bodies and acts as the main joint of the spinal column, occupying approximately 1/3 of its total height [1,2]. The cells within each of the regions of the IVD are subjected to a variety of signals from both physical and biochemical stimuli from their surrounding extracellular matrix (ECM) microenvironment [3–8]. These cues are believed to play critical roles in regulating development, maintenance, and repair of the IVD, but in ways that are poorly understood. Fig. 1 The intervertebral disc is situated between vertebral bodies in the spinal column, and acts to support loads, provide flexibility, and dissipate energy in the spine. The disc is comprised of distinct anatomic zones: the anulus fibrosus (AF), nucleus pulposus ... During disc degeneration or aging, significant changes are observed in IVD cell phenotype and density in parallel with changes in ECM composition and structure. A dramatic decrease in cell density and multicell clusters in both the NP and AF regions is observed [9–11] with increased prevalence of cells with cytoplasmic projections [12–14]. While the exact factors resulting in decreased NP cell clustering with age in vivo are not fully understood, it is likely that cell death associated with decreased nutrient oxygen and glucose transport to the IVD can contribute to these decreased cell numbers and cell clusters [2]. With decreases in cell density, the large, vacuolated cells in the NP, which are normally arranged in cell clusters, transition to a sparse population of smaller, isolated chondrocyte-like cells [15]. The loss of proteoglycan matrix causes changes in proteoglycan structure [16–18], which results in decreased negative fixed-charge density, decreased water content, and a loss of swelling pressure [19,20], impairing the tissue's ability to resist and redistribute compressive loads. Corresponding with these compositional changes are structural alterations including loss of disc height and increased anulus lamellar disorganization. Changes in ECM composition and structure may also result in substantially altered mechanics and kinematics for the entire IVD motion segment, with decreased internal pressurization and disc height resulting in higher compressive loads transferred to the AF, compromising its structure and function (e.g., overload leading to clefts, buckling, or rupture). Nerve compression, spinal canal impingement, and altered spinal loading configurations can also occur, which can contribute to symptomatic back pain [21]. These dramatic shifts in ECM mechanical environment can be expected to impact NP cell health, metabolism and survival, although the direct links between environmental factors and NP cell behaviors are still under study. The purpose of this article is to review our experience with studies of NP cell interactions with their surrounding ECM, as this knowledge can be useful in the development of treatments for disc-related ailments. The first section of this article covers what we have learned of how NP cells interact with select proteins of the native ECM. We then describe how changes in the surrounding ECM can alter NP cell phenotype and morphology, and summarize recent work performed to reveal how NP cells sense, interpret, and respond to different mechanical and biochemical cues in their ECM.

Achilles tendon ruptures are traumatic injuries, and techniques for assessing repair outcomes rely on patient-based measures of pain and function, which do not directly assess tendon healing. Consequently, there is a need for a quantitative, in vivo measure of tendon properties. Therefore, the purpose of this study was to validate ultrasound imaging for evaluating collagen organization in tendons. In this study, we compared our novel, high-frequency ultrasound (HFUS) imaging and analysis method to a standard measure of collagen organization, crossed polarizer (CP) imaging. Eighteen mouse Achilles tendons were harvested and placed into a testing fixture where HFUS and CP imaging could be performed simultaneously in a controlled loading environment. Two experiments were conducted: (1) effect of loading on collagen alignment and (2) effect of an excisional injury on collagen alignment. As expected, it was found that both the HFUS and CP methods could reliably detect an increase in alignment with increasing load, as well as a decrease in alignment with injury. This HFUS method demonstrates that structural measures of collagen organization in tendon can be determined through ultrasound imaging. This experiment also provides a mechanistic evaluation of tissue structure that could potentially be used to develop a targeted approach to aid in rehabilitation or monitor return to activity after tendon injury.

One's ability to exert controlled forces on the environment, such as when manipulating fragile objects, is very important in everyday life. This suggests that force regulation is a necessary component of motor control. In robotics, an effective way to implement force control is by imposing a low contact impedance with critical damping, and using admittance control to regulate force output [1,2]. Human limbs can be modeled as second order mechanical systems, under the assumption that tendons are much stiffer than muscle fibers. The mechanical properties of muscle fibers alone render the implementation of the aforementioned direct force control strategy as not efficient. Several studies have demonstrated that the exertion of force onto the environment results in an increase in muscle stiffness [3–5] and a reduction of muscle damping to under critical values [6,7]. Modeling tendons and contractile elements independently requires higher than second order muscle-tendon models [8]. The presence of a tendon elastic element favors an oscillatory response to external disturbances that normally needs to be eliminated [9]. We demonstrated that a higher order model always exhibits an oscillatory free response and cannot be critically dampened for mechanical parameters included within the normal physiological range. This requires the force controller implemented by the central nervous system (CNS) to employ active feedback and feed-forward regulation. We propose that oscillations, whether part of an external disturbance or of the system's response, can be actively compensated for by the CNS with a position control approach, as long as a predictive model of the perturbation, and an internal model of the system's biomechanics are available. This model of control is in agreement with findings previously published by our group that showed how the implementation of an internal feed-forward model trajectory can be part of a force-regulation strategy [10].

An 8 -mol. % Y2O3-doped zirconia/10-mol. % GdO2-doped ceria (YSZ/GDC) bilayer electrolyte and a Gd0.5Sr0.5CoO3 (GSCO) cathode were deposited by a single-processing, pulsed laser deposition (PLD) method to fabricate anode support cells. No additional heat treatment was needed. Laser frequencies of 10, 20, and 100 Hz were used to deposit bilayer electrolytes between the NiO–YSZ (NiO:YSZ = 60:40 wt. %) anode substrate and the GSCO cathode thin film. The GDC thin film produced at 10 Hz was smooth, well-crystallized, and highly dense. The crystallinity of the GSCO cathode on the GDC was also improved. We concluded the GDC crystallinity affected the crystallinity of the cathode thin film. The resistivity of the YSZ single layer (5.7 μm thickness) was 1.4 times higher than that of the YSZ/GDC bilayer (YSZ 3.0 μm thickness, GDC 2.7 μm thickness) at 600 °C and that of the YSZ-GDC interface became low. The optimum YSZ thickness was found to be approximately 3.0 μm, at which thickness there was effective blocking of the passage of hydrogen molecules and electrons. A cell with a YSZ (3.0 μm thickness, fabricated at 20 Hz)/GDC (5.0 μm thickness, fabricated at 10 Hz) bilayer and GSCO cathode thin film exhibited a maximum power density of 400 mW·cm–2 at a comparatively low temperature of 600 °C.

This study presents a methodology to determine thumb and index finger kinematics while utilizing a minimal set of markers. The motion capture of skin-surface markers presents inherent challenges for the accurate and comprehensive measurement of digit kinematics. As such, it is desirable to utilize robust methods for assessing digit kinematics with fewer markers. The approach presented in this study involved coordinate system alignment, locating joint centers of rotation, and a solution model to estimate three-dimensional (3-D) digit kinematics. The solution model for each digit was based on assumptions of rigid-body interactions, specific degrees of freedom (DOFs) at each located joint, and the aligned coordinate system definitions. Techniques of inverse kinematics and optimization were applied to calculate the 3-D position and orientation of digit segments during pinching between the thumb and index finger. The 3-D joint center locations were reliably fitted with mean coefficients of variation below 5%. A parameterized form of the solution model yielded feasible solutions that met specified tolerance and convergence criteria for over 85% of the test points. The solution results were intuitive to the pinching function. The thumb was measured to be rotated about the CMC joint to bring it into opposition to the index finger and larger rotational excursions (>10 deg) were observed in flexion/extension compared to abduction/adduction and axial rotation for all joints. While the solution model produced results similar to those computed from a full marker set, the model facilitated the usage of fewer markers, which inherently lessened the effects of passive motion error and reduced the post-experimental effort required for marker processing.

In this work, a semiactive electromagnetic vibration absorber has been developed based on a proposed electromagnetic stiffness adjustable spring model, which presents a new solution for adjusting stiffness in the field of vibration absorber devices. Simulation study on the electromagnetic spring has been performed to determine the structural parameter of the semiactive vibration absorber. An experimental rig is also built up to investigate its practical vibration control effectiveness. Firstly, the finite element model of the test bench is used to analyze its vibration characteristics. Then, the vibration reduction effect is predicted through the simulation analysis, from which the optimal control positions are found. Finally, the experimental studies are also conducted, and the results show that this semiactive electromagnetic vibration absorber has a frequency adjustment range from 21 Hz to 25 Hz, in which considerable vibration reduction from 5 dB to 10 dB can be achieved.

Abdominal aortic aneurysm (AAA) is an irreversible, localized growth, typically in the infrarenal region of the aorta. Nearly 8% of the population above 65 years old is diagnosed with this disease [1], which has been shown to be associated with smoking history, heredity, and male gender. As it is asymptomatic, vascular surgeons may opt for surgical intervention or follow a wait-and-watch strategy if their assessment of the risk of rupture is low. Different criteria, such as maximum diameter, growth rate, wall stiffness, thickness of intraluminal thrombus (ILT), wall tension, etc., have been proposed for predicting rupture risk [2], which should be weighed against the risk of surgery, given that most AAA patients are elderly. The maximum diameter criterion is widely used in clinical practice [3], with the threshold diameter for decision making (typically 5.5 cm) following an evidence-based approach. However, an autopsy study of 473 AAA cases found that 13% of aneurysms 5 cm in diameter or smaller ruptured, whereas 60% of aneurysms of diameter greater than 5 cm did not [4]. Diameter-based rules for rupture prediction fail for 10%–25% patients in small and large AAA [5]. Hence, there is a clear need to accurately assess rupture risk on a patient-specific basis by using more rigorous, scientific means. A biomechanics-based approach can be helpful toward achieving this goal by accurately modeling the individual AAA geometry. Wall thickness is an important geometry variable that can potentially increase the accuracy of AAA biomechanical analysis. Rupture is a local phenomenon that should be assessed by modeling spatially varying local geometry, thereby eliminating the role of globally defined criteria, such as diameter and sac volume for patient-specific rupture risk analysis. Vascular wall thickness is believed to be an influential geometric feature for biomechanical stress evaluation. From a mechanics perspective, the shape of an aneurysm and the thickness of the artery should govern dominantly the stress distribution compared to the overall size of the aneurysm [6]. Acknowledging that there are limitations inherent to image acquisition sequences and resolution, deriving accurate segmentation and geometric modeling algorithms are highlighted as open problems in computational vascular biomechanics [7]. Thickness, nonlinear material behavior, strength of the AAA wall, and the spatial distribution of these variables are said to be essential for achieving accurate finite element (FE) simulations and, therefore, also for a realistic prediction of AAA rupture risk [8,9]. Few studies report experimental measurements of aneurysmatic wall thickness [10–12,33] and with large differences in their findings, as described in Table ​Table1.1. The autopsy-based observation that AAA rupture location occurs mostly on the posterior wall [4] is in agreement with the finding by Raghavan et al. [11] that wall thickness is slightly less in the posterior region compared to the anterior region. It should be noted that the severity of a posterior wall rupture is relatively less than that of an anterior wall rupture. Hence, it is more likely that posterior wall rupture cases are documented in the medical literature, since a patient with anterior wall rupture may not reach a hospital alive, thereby compounding the aforementioned observations. In a healthy aorta, the anterior wall is thicker than the posterior [10] and with a mean wall thickness of 1.39 mm [13]. The challenge of estimating regional variations of wall thickness and the subsequent incorporation in FE analysis is a complex one. Hence, the assumption of a uniform wall thickness in numerical models reported in the literature is questionable, and there is need for addressing whether the regional variations are needed on a patient-specific basis. To that end, Martufi et al. [14] reported the validation of a set of matlab routines for estimating regional vessel wall thickness from CT images by comparing it with postmortem AAA tissue measurements [11], resulting in an average relative difference of 7.8%. A framework for semiautomatic vessel wall detection and quantification of thickness using contrast-enhanced CT images was described by Shum et al. [15], resulting in low repeatability and reproducibility errors when compared to the manual segmentations performed by trained vascular surgeons. Quantitative assessment of AAA geometry [16] has shown promising results, with wall thickness being one of the morphological indicators significant for rupture risk stratification. These developments are paving the way for noninvasive, automatic geometric assessment of AAAs yielding population stratification in clinical practice. Table 1 Brief summary of previously reported experimental measurements on wall thickness (eAAA—electively repaired AAA; rAAA—ruptured AAA)

The current study was performed to evaluate the accuracy of computational assessment of the influence of the orientation of the patellar tendon on the patellofemoral pressure distribution. Computational models were created to represent eight knees previously tested at 40 deg, 60 deg, and 80 deg of flexion to evaluate the influence of hamstrings loading on the patellofemoral pressure distribution. Hamstrings loading increased the lateral and posterior orientation of the patellar tendon, with the change for each test determined from experimentally measured variations in tibiofemoral alignment. The patellar tendon and the cartilage on the femur and patella were represented with springs. After loading the quadriceps, the total potential energy was minimized to determine the force within the patellar tendon. The forces applied by the quadriceps and patellar tendon produced patellar translation and rotation. The deformation of each cartilage spring was determined from overlap of the cartilage surfaces on the femur and patella and related to force using linear elastic theory. The patella was iteratively adjusted until the extension moment, tilt moment, compression, and lateral force acting on the patella were in equilibrium. For the maximum pressure applied to lateral cartilage and the ratio of the lateral compression to the total compression, paired t-tests were performed at each flexion angle to determine if the output varied significantly (p

To prevent primary water stress corrosion cracking (PWSCC), water jet peening (WJP) has been used on the welds of Ni-based alloys in pressurized water reactors (PWRs). Before WJP, the welds are machined and buffed in order to conduct a penetrant test (PT) to verify the weld qualities to access, and microstructure evolution takes place in the target area due to the severe plastic deformation. The compressive residual stresses induced by WJP might be unstable under elevated temperatures because of the high dislocation density in the compressive stress layer. Therefore, the stability of the compressive residual stresses caused by WJP was investigated during long-term operation by considering the microstructure evolution due to the working processes. The following conclusions were made: The compressive residual stresses were slightly relaxed in the surface layers of the thermally aged specimens. There were no differences in the magnitude of the relaxation based on temperature or time. The compressive residual stresses induced by WJP were confirmed to remain stable under elevated temperatures. The stress relaxation at the surface followed the Johnson–Mehl equation, which states that stress relaxation can occur due to the recovery of severe plastic strain, since the estimated activation energy agrees very well with the self-diffusion energy for Ni. By utilizing the additivity rule, it was indicated that stress relaxation due to recovery is completed during the startup process. It was proposed that the long-term stability of WJP under elevated temperatures must be assessed based on compressive stresses with respect to the yield stress. Thermal elastic–plastic creep analysis was performed to predict the effect of creep strain. After 100 yr of simulated continuous operation at 80% capacity, there was little change in the WJP compressive stresses under an actual operating temperature of 623 K. Therefore, the long-term stability of WJP during actual operation was analytically predicted.

We present three-dimensional numerical simulations of hydrodynamic interaction between a red blood cell (RBC) and a platelet in a wall-bounded shear flow. The dynamics and large deformation of the RBC are fully resolved in the simulations using a front-tracking method. The objective is to quantify the influence of tank treading and tumbling dynamics of the RBC, and the presence of a bounding wall on the deflection of platelet trajectories. We observe two types of interaction: A crossing event in which the platelet comes in close proximity to the RBC, rolls over it, and continues to move in the same direction; and a turning event in which the platelet turns away before coming close to the RBC. The crossing events occur when the initial lateral separation between the cells is above a critical separation, and the turning events occur when it is below the critical separation. The critical lateral separation is found to be higher during the tumbling motion than that during the tank treading. When the RBC is flowing closer to the wall than the platelet, the critical separation increases by several fold, implying the turning events have higher probability to occur than the crossing events. On the contrary, if the platelet is flowing closer to the wall than the RBC, the critical separation decreases by several folds, implying the crossing events are likely to occur. Based on the numerical results, we propose a mechanism of continual platelet drift from the RBC-rich region of the vessel towards the wall by a succession of turning and crossing events. The trajectory deflection in the crossing events is found to depend nonmonotonically on the initial lateral separation, unlike the monotonic trend observed in tracer particle deflection and in deformable sphere-sphere collision. This nonmonotonic trend is shown to be a consequence of the deformation of the RBC caused by the platelet upon collision. An estimation of the platelet diffusion coefficient yields values that are similar to those reported in experiments and computer simulations with multicellular suspension.

While useful models have been proposed to predict the mechanical impact of damage in tendon and other soft tissues, the applicability of these models for describing in vivo injury and age-related degeneration has not been investigated. Therefore, the objective of this study was to develop and validate a simple damage model to predict mechanical alterations in mouse patellar tendons after aging, injury, or healing. To characterize baseline properties, uninjured controls at age 150 days were cyclically loaded across three strain levels and five frequencies. For comparison, damage was induced in mature (120 day-old) mice through either injury or aging. Injured mice were sacrificed at three or six weeks after surgery, while aged mice were sacrificed at either 300 or 570 days old. Changes in mechanical properties (relative to baseline) in the three week post-injury group were assessed and used to develop an empirical damage model based on a simple damage parameter related to the equilibrium stress at a prescribed strain (6%). From the derived model, the viscoelastic properties of the 300 day-old, 570 day-old, and six week post-injury groups were accurately predicted. Across testing conditions, nearly all correlations between predicted and measured parameters were statistically significant and coefficients of determination ranged from R2 = 0.25 to 0.97. Results suggest that the proposed damage model could exploit simple in vivo mechanical measurements to predict how an injured or aged tendon will respond to complex physiological loading regimens.

Muscle-driven simulations of human and animal motion are widely used to complement physical experiments for studying movement dynamics. Musculotendon models are an essential component of muscle-driven simulations, yet neither the computational speed nor the biological accuracy of the simulated forces has been adequately evaluated. Here we compare the speed and accuracy of three musculotendon models: two with an elastic tendon (an equilibrium model and a damped equilibrium model) and one with a rigid tendon. Our simulation benchmarks demonstrate that the equilibrium and damped equilibrium models produce similar force profiles but have different computational speeds. At low activation, the damped equilibrium model is 29 times faster than the equilibrium model when using an explicit integrator and 3 times faster when using an implicit integrator; at high activation, the two models have similar simulation speeds. In the special case of simulating a muscle with a short tendon, the rigid-tendon model produces forces that match those generated by the elastic-tendon models, but simulates 2–54 times faster when an explicit integrator is used and 6–31 times faster when an implicit integrator is used. The equilibrium, damped equilibrium, and rigid-tendon models reproduce forces generated by maximally-activated biological muscle with mean absolute errors less than 8.9%, 8.9%, and 20.9% of the maximum isometric muscle force, respectively. When compared to forces generated by submaximally-activated biological muscle, the forces produced by the equilibrium, damped equilibrium, and rigid-tendon models have mean absolute errors less than 16.2%, 16.4%, and 18.5%, respectively. To encourage further development of musculotendon models, we provide implementations of each of these models in OpenSim version 3.1 and benchmark data online, enabling others to reproduce our results and test their models of musculotendon dynamics.

Magnetic iron oxide nanoparticles (mNP), magnetite and mag-hemite, are under investigation as a means to provide a favorable therapeutic ratio for local hyperthermia treatment of tumors, and to make localized heating of the tumor less engineering-intensive and more cancer cell specific. They have been used successfully to localize tumor heating in experimental animals and in vitro [1–10]. Heating of nanoparticles is complicated by the short thermal relaxation time constants and difficulty of coupling sufficient power to achieve desired temperatures without creating toxic eddy currents in the tissues. Rabin [11] argues convincingly that individual (i.e., dispersed) nanoparticles are not able to effectively heat cells and tissues in electromagnetic fields because their small size results in extremely short thermal time constants, and the power densities required are too high to be practical. Nevertheless, experimental evidence shows that sufficient nanoparticle heating can be achieved with the same magnetic nanoparticles if spatially appropriate aggregates of NPs can be achieved; but clustering of the particles is essential to achieve useful results [5,12]. Magnetic field heating of iron oxide nanoparticles is typically accomplished by the hysteresis loop mechanism in alternating magnetic fields (AMFs), either due to Neel relaxation, Brownian motion, or perhaps, particle–particle interaction in super-paramagnetic nanoparticles at frequencies between 100 and 300 kHz, and has proven to be effective. The precise mechanism is somewhat controversial at this point, since it has not been clearly delineated and may consist of a combination of these, and perhaps other, mechanisms. In all cases the heating field is highly local in nature, and effective treatment depends on clustering and the spatial distribution of particles in strategically advantageous locations. To date almost all of the germane literature has been confined to experimental studies; the single exception that we have been able to identify is the work of Etheridge and Bischof, which included experiments and numerical models of suspended mNPs in a droplet [13]. Finite element method (FEM) numerical models can also be used to estimate the order of magnitude of volume power density, Q gen (W m−3) required to achieve significant heating in evenly dispersed and aggregated clusters of nanoparticles in more realistic multiple heat transfer and tumor geometry environments, which was one of the goals of this study. The FEM models developed in this study were confined to continuum formulations and did not include film nano-dimension heat transfer effects at the nanoparticle surface. The models illustrate the overwhelming effect of local heat transfer processes and the multiscale nature of the root problem. We develop and implement approximate numerical model approaches that illuminate the relative importance of biodistribution of mNPs and the local heat transfer boundary conditions. The results make practical ordinary sized FEM models of larger geometries and should facilitate the eventual engineering design and analysis of nanoparticle heating in realistic tumor-sized systems. While tumor-sized model spaces have not yet been developed, the pathway to do so is identified and described.

A soft tissue's macroscopic behavior is largely determined by its microstructural components (often a collagen fiber network surrounded by a nonfibrillar matrix (NFM)). In the present study, a coupled fiber-matrix model was developed to fully quantify the internal stress field within such a tissue and to explore interactions between the collagen fiber network and nonfibrillar matrix (NFM). Voronoi tessellations (representing collagen networks) were embedded in a continuous three-dimensional NFM. Fibers were represented as one-dimensional nonlinear springs and the NFM, meshed via tetrahedra, was modeled as a compressible neo-Hookean solid. Multidimensional finite element modeling was employed in order to couple the two tissue components and uniaxial tension was applied to the composite representative volume element (RVE). In terms of the overall RVE response (average stress, fiber orientation, and Poisson's ratio), the coupled fiber-matrix model yielded results consistent with those obtained using a previously developed parallel model based upon superposition. The detailed stress field in the composite RVE demonstrated the high degree of inhomogeneity in NFM mechanics, which cannot be addressed by a parallel model. Distributions of maximum/minimum principal stresses in the NFM showed a transition from fiber-dominated to matrix-dominated behavior as the matrix shear modulus increased. The matrix-dominated behavior also included a shift in the fiber kinematics toward the affine limit. We conclude that if only gross averaged parameters are of interest, parallel-type models are suitable. If, however, one is concerned with phenomena, such as individual cell-fiber interactions or tissue failure that could be altered by local variations in the stress field, then the detailed model is necessary in spite of its higher computational cost.

The use of compliance chambers in mock circulatory loop construction is the predominant means of simulating arterial compliance. Utilizing mock circulatory loops as bench test methods for cardiac assist technologies necessitates that they must be capable of reproducing the circulatory conditions that would exist physiologically. Of particular interest is the ability to determine instantaneous compliance of the system, and the ability to change the compliance in real-time. This capability enables continuous battery testing of conditions without stopping the flow to change the compliance chamber settings, and the simulation of dynamic changes in arterial compliance. The method tested involves the use of a compliance chamber utilizing a circular natural latex rubber membrane separating the fluid and air portions of the device. Change in system compliance is affected by the airspace pressure, which creates more reaction force at the membrane to the fluid pressure. A pressure sensor in the fluid portion of the chamber and a displacement sensor monitoring membrane center deflection allow for real-time inputs to the control algorithm. A predefined numerical model correlates the displacement sensor data to the volume displacement of the membrane. The control algorithm involves a tuned π loop maintaining the volume distention of the membrane via regulation of the air space pressure. The proportional integral (PI) controller tuning was achieved by creating a computational model of the compliance chamber using Simulink™ Simscape® toolboxes. These toolboxes were used to construct a model of the hydraulic, mechanical, and pneumatic elements in the physical design. Parameter Estimation™ tools and Design Optimization™ methods were employed to determine unknown physical parameters in the system, and tune the process controller used to maintain the compliance setting. It was found that the resulting control architecture was capable of maintaining compliance along a pressure-volume curve and allowed for changes to the compliance set point curve without stopping the pulsatile flow.

One of the primary limitations of cell therapy for myocardial infarction is the low survival of transplanted cells, with a loss of up to 80% of cells within 3 days of delivery. The aims of this study were to investigate the distribution of nutrients and oxygen in infarcted myocardium and to quantify how macromolecular transport properties might affect cell survival. Transmural myocardial infarction was created by controlled cryoablation in pigs. At 30 days post-infarction, oxygen and metabolite levels were measured in the peripheral skeletal muscle, normal myocardium, the infarct border zone, and the infarct interior. The diffusion coefficients of fluorescein or FITC-labeled dextran (0.3–70 kD) were measured in these tissues using fluorescence recovery after photobleaching. The vascular density was measured via endogenous alkaline phosphatase staining. To examine the influence of these infarct conditions on cells therapeutically used in vivo, skeletal myoblast survival and differentiation were studied in vitro under the oxygen and glucose concentrations measured in the infarct tissue. Glucose and oxygen concentrations, along with vascular density were significantly reduced in infarct when compared to the uninjured myocardium and infarct border zone, although the degree of decrease differed. The diffusivity of molecules smaller than 40 kD was significantly higher in infarct center and border zone as compared to uninjured heart. Skeletal myoblast differentiation and survival were decreased stepwise from control to hypoxia, starvation, and ischemia conditions. Although oxygen, glucose, and vascular density were significantly reduced in infarcted myocardium, the rate of macromolecular diffusion was significantly increased, suggesting that diffusive transport may not be inhibited in infarct tissue, and thus the supply of nutrients to transplanted cells may be possible. in vitro studies mimicking infarct conditions suggest that increasing nutrients available to transplanted cells may significantly increase their ability to survive in infarct.

Recent advances in the treatment of cancer involving therapeutic agents have shown promising results. However, treatment efficacy can be limited due to inadequate and uneven uptake in solid tumors, thereby making the prediction of drug transport important for developing effective therapeutic strategies. In this study, a patient-specific computational porous media model (voxelized model) was developed for predicting the interstitial flow field and distribution of a systemically delivered magnetic resonance (MR) visible tracer in a tumor. The benefits of a voxel approach include less labor and less computational time (approximately an order of magnitude reduction compared to the traditional computational fluid dynamics (CFD) approach developed earlier by our group). The model results were compared with that obtained from a previous approach based on unstructured meshes along with MR-measured tracer concentration data within tumors, using statistical analysis and qualitative representations. The statistical analysis indicated the similarity between the structured and unstructured models’ results with a low root mean square error (RMS) and a high correlation coefficient. The voxelized model captured features of the flow field and tracer distribution such as high interstitial fluid pressure inside the tumor and the heterogeneous distribution of the tracer. Predictions of tracer distribution by the voxelized approach also resulted in low RMS error when compared with MR-measured data over a 1 h time course. The similarity in the voxelized model results with experiment and the nonvoxelized model predictions were maintained across three different tumors. Overall, the voxelized model serves as a reliable and swift alternative to approaches using unstructured meshes in predicting extracellular transport within tumors.

The heterogeneous composition and mechanical properties of the supraspinatus tendon offer an opportunity for studying the structure-function relationships of fibrous musculoskeletal connective tissues. Previous uniaxial testing has demonstrated a correlation between the collagen fiber angle distribution and tendon mechanics in response to tensile loading both parallel and transverse to the tendon longitudinal axis. However, the planar mechanics of the supraspinatus tendon may be more appropriately characterized through biaxial tensile testing, which avoids the limitation of nonphysiologic traction-free boundary conditions present during uniaxial testing. Combined with a structural constitutive model, biaxial testing can help identify the specific structural mechanisms underlying the tendon’s two-dimensional mechanical behavior. Therefore, the objective of this study was to evaluate the contribution of collagen fiber organization to the planar tensile mechanics of the human supraspinatus tendon by fitting biaxial tensile data with a structural constitutive model that incorporates a sample-specific angular distribution of nonlinear fibers. Regional samples were tested under several biaxial boundary conditions while simultaneously measuring the collagen fiber orientations via polarized light imaging. The histograms of fiber angles were fit with a von Mises probability distribution and input into a hyperelastic constitutive model incorporating the contributions of the uncrimped fibers. Samples with a wide fiber angle distribution produced greater transverse stresses than more highly aligned samples. The structural model fit the longitudinal stresses well (median R2 ≥ 0.96) and was validated by successfully predicting the stress response to a mechanical protocol not used for parameter estimation. The transverse stresses were fit less well with greater errors observed for less aligned samples. Sensitivity analyses and relatively affine fiber kinematics suggest that these errors are not due to inaccuracies in measuring the collagen fiber organization. More likely, additional strain energy terms representing fiber-fiber interactions are necessary to provide a closer approximation of the transverse stresses. Nevertheless, this approach demonstrated that the longitudinal tensile mechanics of the supraspinatus tendon are primarily dependent on the moduli, crimp, and angular distribution of its collagen fibers. These results add to the existing knowledge of structure-function relationships in fibrous musculoskeletal tissue, which is valuable for understanding the etiology of degenerative disease, developing effective tissue engineering design strategies, and predicting outcomes of tissue repair.

The human lung comprises about 300 million alveoli which are located on bronchioles between the 17th to 24th generations of the acinar tree, with a progressively higher population density in the deeper branches (lower acini). The alveolar size and aspect ratio change with generation number. Due to successive bifurcation, the flow velocity magnitude also decreases as the bronchiole diameter decreases from the upper to lower acini. As a result, fluid dynamic parameters such as Reynolds (Re) and Womersley (α) numbers progressively decrease with increasing generation number. In order to characterize alveolar flow patterns and inhaled particle transport during synchronous ventilation, we have conducted measurements for a range of dimensionless parameters physiologically relevant to the upper acini. Acinar airflow patterns were measured using a simplified in vitro alveolar model consisting of a single transparent elastic truncated sphere (representing the alveolus) mounted over a circular hole on the side of a rigid circular tube (representing the bronchiole). The model alveolus was capable of expanding and contracting in-phase with the oscillatory flow through the bronchiole thereby simulating synchronous ventilation. Realistic breathing conditions were achieved by exercising the model over a range of progressively varying geometric and dynamic parameters to simulate the environment within several generations of the acinar tree. Particle image velocimetry was used to measure the resulting flow patterns. Next, we used the measured flow fields to calculate particle trajectories to obtain particle transport and deposition statistics for massless and finite-size particles under the influence of flow advection and gravity. Our study shows that the geometric parameters (β and ΔV/V) primarily affect the velocity magnitudes, whereas the dynamic parameters (Re and α) distort the flow symmetry while also altering the velocity magnitudes. Consequently, the dynamic parameters have a greater influence on the particle trajectories and deposition statistics compared to the geometric parameters. The results from this study can benefit pulmonary research into the risk assessment of toxicological inhaled aerosols, and the pharmaceutical industry by providing better insight into the flow patterns and particle transport of inhalable therapeutics in the acini.