Indiana University-Purdue University Indianapolis (IUPUI) / Current interventions used to reduce skeletal fragility are insufficient at enhancing bone across multiple hierarchical levels. Bisphosphonates, such as Zoledronate (ZOL), treat a variety of bone disorders by increasing bone mass and bone mineral density to decrease fracture risk. Despite the mass-based improvements, bisphosphonate use has been shown to compromise bone quality. Alternatively, Raloxifene (RAL) has recently been demonstrated to improve tissue quality and overall mechanical properties by binding to collagen and increasing tissue hydration in a cell-independent manner. We hypothesized that a combination of RAL and ZOL would improve mechanical and material properties of bone more than either monotherapy alone by enhancing both quantity and quality of bone. In this study, wildtype (WT) and heterozygous (OIM+/-) male mice from the Osteogenesis Imperfecta (OI) murine model were treated with either RAL, ZOL, or RAL and ZOL from 8 weeks to 16 weeks of age. Combination treatment resulted in higher trabecular architecture, cortical mechanical properties, and cortical fracture toughness in diseased mouse bone. Two fracture toughness properties, direct measures of the tissue’s ability to resist the initiation and propagation of a crack, were significantly improved with combination treatment in OIM+/- compared to control. There was no significant effect on fracture toughness with either monotherapy alone in either genotype. Following the mass-based effects of ZOL, bone volume fraction was significantly higher with combination treatment in both genotypes. Similar results were seen in trabecular number. Combination treatment resulted in higher ultimate stress in both genotypes, with RAL additionally increasing ultimate stress in OIM+/-. RAL and combination treatment in OIM+/- also produced a higher resilience compared to the control. Given no significant changes in cortical geometry, these mechanical alterations were likely driven by the quality-based effects of RAL. In conclusion, this study demonstrates the beneficial effects of using combination therapy to increase bone mass while simultaneously improving tissue quality, especially to enhance the mechanical integrity of diseased bone. Combination therapies could be a future mechanism to improve bone health and combat skeletal fragility on multiple hierarchical levels.

The non-invasive differential diagnosis of breast masses through ultrasound imaging motivates the following class of elastic inverse problems: Given one or more measurements of the displacement field within an elastic material, determine the material property distribution within the material. This thesis is focused on uncertainty quantification in inverse problem solutions, with application to inverse problems in linear and nonlinear elasticity. We consider the inverse nonlinear elasticity problem in the context of Bayesian statistics. We show the well-known result that computing the Maximum A Posteriori (MAP) estimate is consistent with previous optimization formulations of the inverse elasticity problem. We show further that certainty in this estimate may be quantified using concepts from information theory, specifically, information gain as measured by the Kullback-Leibler (K-L) divergence and mutual information. A particular challenge in this context is the computational expense associated with computing these quantities. A key contribution of this work is a novel approach that exploits the mathematical structure of the inverse problem and properties of conjugate gradient method to make these calculations feasible. A focus of this work is estimating the spatial distribution of the elastic nonlinearity of a material. Measurement sensitivity to the nonlinearity is much higher for large (finite) strains than for smaller strains, and so large strains tend to be used for such measurements. Measurements of larger deformations, however, tend to show greater levels of noise. A key finding of this work is that, when identifying nonlinear elastic properties, information gain can be used to characterize a trade-off between larger strains with higher noise levels and smaller strains with lower noise levels. These results can be used to inform experimental design. An approach often used to estimate both linear and nonlinear elastic property distributions is to do so sequentially: Use a small strain deformation to estimate the linear properties, and a large strain deformation to estimate the nonlinearity. A key finding of this work is that accurate characterization of the joint posterior probability distribution over both linear and nonlinear elastic parameters requires that the estimates be performed jointly rather than sequentially. All the methods described above are demonstrated in applications to problems in elasticity for both simulated data as well as clinically measured data (obtained in vivo). In the context of the clinical data, we evaluate repeatability of measurements and parameter reconstructions in a clinical setting.

Exoskeletons for rehabilitation commonly focus on gait training, despite the variety of human movements and functional assistance needed. Cable-driven exoskeletons have an advantage in addressing a variety of movements by being non-restrictive in their design. Additionally, these devices do not require complex mechanical joints to apply forces on the user or hinder the user's mobility. This accommodation of movement makes these cable-driven architectures more suitable for everyday movement. However, these flexible cable-driven exoskeletons often actuate a reduced number of actuated degrees-of-freedom to simplify their mechanical complexity. There is a need to design flexible and low-profile cable-driven exoskeletons to accommodate the movement of the user and be more flexible in their ability to actuate them. This thesis presents cable-driven exoskeleton designs that are used during walking and or squatting. These exoskeletons can be reconfigured to apply forces that are appropriate for these functional tasks. The three designs presented in this thesis are non-restrictive cable-driven designs that add minimal weight to the user. The first design shown is the cable-driven active leg exoskeleton previously developed by the Robotics and Rehabilitation Laboratory (C-ALEX, 10kg). The second and third designs are novel cable-driven architectures: (i) the modular C-ALEX (mC-ALEX, 3kg) and (ii) the soft C-ALEX (SC-ALEX, <1kg). A preliminary evaluation of the latter two devices was performed, and the results of these studies are presented to better understand the limitations and abilities of each design. The functionalities added to the latter two designs include the ability to reconfigure the robot's cable routing and attachment geometry, allowing the devices to apply torques through cables in the non-sagittal plane. These features will enable the robot to assist in tasks other than gait while still using the original C-ALEX design methods. Another feature added to the exoskeleton controller is to allow visual feedback through an Augmented Reality headset (the HoloLens) to incorporate visual feedback during tasks better. This feature is currently missing from the rehabilitation field using exoskeletons. The effects of using the C-ALEX with post-stroke participants were carried out to ascertain the efficacy of using a cable-driven system for gait adaptations in persons with gait impairments and compare their effectiveness against rigid-linked exoskeletons. The C-ALEX was assessed to induce a change in the walking patterns of ten post-stroke participants using a single-session training protocol. The ability of C-ALEX to accurately provide forces and torques in the desired directions was also evaluated to compare its design performance to traditional rigid-link designs. Participants were able to reach 91% ± 12% of their target step length and 89% ± 13 % of their target step height. The achieved step parameters differed significantly from participant baselines (p <0.05). To quantify the performance, the forces in each cable's out-of-the-plane movements were evaluated relative to the in-plane desired cable tension magnitudes. This corresponded to an error of under 2Nm in the desired controlled joint torques. This error magnitude is low compared to the system command torques and typical adult biological torques during walking (2-4%). These results point to the utility of using non-restrictive cable-driven architectures in gait retraining, in which future focus can be on rehabilitating gait pathologies seen in stroke survivors. Visual and force feedback are common elements in rehabilitation robotics, but visual feedback is difficult to provide in over-ground mobile exoskeleton systems. A preliminary study was carried out to assess the effects of providing force-only, force and visual, or visual-only feedback to three independent groups, each containing 8 participants. The groups showed an increase in normalized step height, (force and visual: 1.10 ± .13, force-only: 1.03 ± .23 visual-only: 1.61 ± .52) and decreased normalized trajectory tracking error (force and visual: 42.8% ± 23.4%, force: 47.6% ± 18.4% , visual-only: 114.2% ± 60.0%). Visual normalized step height differed significantly from force and visual and force-only normalized step height (p<0.005). Lap-wise normalized tracking error differed significantly ($p < 0.005$) within participants. The mC-ALEX and the HoloLens were used to test the effectiveness of robot force feedback compared to visual feedback with a squat task. The squat task aimed to have the user reach targets of 25%, 75%, and 125% of baseline squats depths through each feedback modality. The kinematic and foot loading effects were considered to establish the differences in user behavior when receiving both types of feedback. The results show that visual feedback has lower errors from targets with similar lower variability in user performance. The force feedback changed joint flexion profiles without changing foot loading biomechanics. When looking at the sessions in sequence, both feedback modalities reduced depth error magnitudes further along with the sessions time-wise. This is the first study where augmented in-field-of-view visual feedback and robotic feedback are used with the aim of changing the kinematics of a squatting task. Overall, this thesis contributes to expanding the capabilities of cable-driven exoskeletons in lower limb rehabilitative tasks. Three designs are evaluated to understand their on-user performance, with the latter two devices being novel designs. The devices are used in protocols that include visual feedback to ascertain their effects on movement adaptation through the two feedback modalities.

Graphene is a 2D material well known for its high intrinsic strength of 100 GPa and Young’s modulus of 1 TPa. Because of its 2D nature, the most promising avenues to utilize graphene as a mechanical material include incorporating it as reinforcement in a nanocomposite and creating free-standing foams and aerogels. However, the current techniques are not well-controlled – the reinforcing graphene particles are often discontinuous and randomly dispersed – making it difficult to accurately model and predict the resulting material properties. Here we aim to develop a framework for a new class of nanocomposites reinforced not by discrete nanoparticles, but by a continuous 3D graphene network. These 3D graphene networks were formed by chemical vapor deposition of graphene on periodic metallic microlattices, thereby providing mechanical reinforcement for the lattices. To assist in the lattice design, analytical models were derived for the mechanical properties of core/shell composite lattices and experimentally validated through compression testing of polymer lattices coated with electroless Ni-P. The models and experiments showed good agreement at lower shell thicknesses, while there was divergence at higher thicknesses, likely due to fabrication imperfections. The analytical models were also applied to hollow metallic lattices coated with graphene and compared to experimental data. The results showed that the models are plausible and suggest that graphene has a significant strengthening effect on the microlattices. These studies represent a paradigm shift in the design and fabrication of nanocomposites as one may now precisely prescribe the placement of the reinforcing nanomaterials. On a broader scale, this work also lays the framework for using a 2D material to span 3D space, enabling further exploration of 2D material properties and applications. One potential application area for a graphene-reinforced polymer composite is in prosthetic heart valves. The tissue of a human heart valve leaflet is heavily reinforced with networks of collagen and elastin fibers. One could similarly incorporate a graphene network as reinforcement within the polymeric leaflets of a prosthetic valve. One promising application of polymeric valves is in growth-accommodating implants for pediatric patients. Here we aim to develop a polymeric valved conduit that can be expanded by transcatheter balloon dilation to match a child’s growth. We designed the valve, characterized and selected materials, fabricated the devices and performed benchtop in vitro testing. The first generation of an expandable biostable valved conduit displayed excellent hydrodynamic performance before and after permanent balloon dilation from 22 to 25 mm. The second generation has shown the potential for a greater dilation from 12 to 24 mm. These results demonstrate concept feasibility and motivate further development of a polymeric balloon-expandable device to replace valves in children and avoid reoperations.

No description available.

Natural terrain constantly challenges locomotor stability. Bipedal parasagittal runners rely on proximo-distal control mechanisms and passive mechanical mechanisms to rapidly adjust to changing environments. However, it is not known how sprawled bipedal runners, like the basilisk lizard, adjust to unexpected perturbations. This study examines how basilisks navigate visible drop perturbations to elucidate the control strategies used to maintain stability. We ran four basilisk lizards along a 2.7 m long trackway with an embedded 6-d.o.f. force plate. Control trials were recorded with the force plate mounted flush to the track surface. We lowered the plate to 40% of the lizards’ limb length, relative to the track surface, for perturbation trials. We hypothesized that much like parasagittal runners, basilisks would rely on three distinct compensatory mechanisms to convert the potential energy (PE) change from the drop into fore-aft and vertical kinetic energy (KE) or to increase the total energy of the system (Ecom), as well as a fourth potential mechanism converting PE into medio-lateral KE, as a result of their sprawled limb posture. On average, lizards ran slower (T-ratio30=2.548, p = 0.0162) and with a more vertical limb posture (T-ratio28=-6.119, p &lt; 0.0001) during the drop perturbation. As expected, vertical KE increased in drop surface trials. However, contrary to our hypothesis, the drop perturbation appeared to have little detectable effect on fore-aft and medio-lateral KE. Preliminarily, these results suggest that the sprawled limb posture may afford increased robustness to perturbations such as a sudden drop in surface height, facilitating kinematic compensations independent of significant kinetic changes. / Kinesiology

In the natural world, animals encounter terrestrial environments that range from stiff to compliant. Terrestrial locomotion across natural surfaces is highly complex, as animals must overcome substrate heterogeneity to maintain locomotor performance essential for survival (e.g., catching prey, escaping predators). Within these environments, natural substrates such as sand, gravel and cobbles, are known as granular media: a collection of discrete particles varying in material properties and behaviors when exposed to forces of different magnitude. On a single step, granular media alternates between solid and fluid-like states with potentially drastic consequences on running performance. Additionally, granular substrates at different inclinations are ubiquitous in natural environments, such as sand dunes in the desert. At the angle of repose—the maximum angle providing sand dunes their typical shape—granular media will fluidize with the slightest stress, rendering running at these angles extremely challenging. Unlike locomotion through fluids (e.g., swimming and flying), governed by the Navier-Stokes equations, how foot kinematics instigate state changes on granular media is still poorly understood, yet it is critically important for survival. The goal of my dissertation is to determine how foot use affects foot-ground interactions on granular media, with a particular focus on incline locomotion. The objectives of my dissertation are threefold: evaluate the effects of granular inclines on 1) performance and above-surface limb and foot kinematics, 2) sub-surface foot kinematics, and 3) the dynamics of foot-ground interactions using computational simulations. To fulfill these objectives, I examined three lizard species: a sand specialist (Callisaurus draconoides), a desert generalist (Crotaphytus bicinctores), and a fluid specialist (Basiliscus vittatus), selected because they have similarly shaped feet, so that differences detected among performance are due to foot kinematics rather than morphology. I ran these lizard species on a level and inclined granular trackway, while videorecording them at 500 fps using a high-speed video camera (light video) and a bi-planar high-speed fluoroscopy system (X-ray video) for the above-surface kinematics and the subsurface kinematics, respectively. Running trials were used to quantify running speed, basic stride, foot impact, and sub-surface foot kinematics, to implement on computational simulations of foot-shaped intruders entering a volume of particles to quantify force response at the particle scale. Sand specialists not only outperformed non-specialists on the incline, but maintained running speed compared to the level despite presenting some foot slip. While no significant differences across species were found for basic stride and impact kinematics, only sand specialists shifted foot intrusion angle into incline granular media to angles close to perpendicular to the substrate. At the subsurface, sand specialists maintained a stiffer foot similar to generalists, and intruded their feet shallower similar to fluid specialists. However, only sand specialists maintained toe spacings close to 6 mm on level and incline, similar to a study on intruder spacings showing peak force generation. The ground force response exhibited by the sand specialist lizard foot model revealed that by hitting the particles fast (0.7 m/s) and shallow, almost perpendicular to the substrate, toe first, with stiff feet, and toe spacings close to 6 mm, sand specialists are likely taking advantage of the inertial behavior of the particles at the angle of repose. Essentially, by paddling through the substrate’s fluid-like behaving surface, sand specialists run significantly faster than fluid specialists and generalists. My dissertation demonstrates the significance of surface and subsurface kinematics strategies to understand foot-ground interactions, especially on angled yielding substrates, contributing with knowledge to the terradynamics field and elucidating significant applications in bioengineering, bioinspiration and robotics. / Biology

With Athletes and individuals developing osteoarthritis and chondral defects at younger ages, long term treatments are in high demand. Total knee replacements only last for 10-15 years, so younger individuals would need to have multiple knee replacements within their lifetime. Allograft transplantation has shown to last long term and have high success rates, but the lack of donors and the possibility of damaging other areas of the knee to obtain tissue grafts has become a large concern. Xenografts derived from porcine cartilage is cost effective and the supply is abundant. Two antigen removal processes were examined: a short term antigen removal process to maintain the mechanical stability of the tissue, and a long antigen removal process to minimize the risk of triggering an immune response. The antigen removal processes were compared, and the future precautions were determined to enhance the probability of creating a viable osteochondral xenograft preparation technique.

No description available.

<p>Our healthcare system is experiencing a substantial economic burden, and one of the contributing factors is ankle injury - particularly ankle sprains - and the resulting chronic conditions like ankle instability and osteoarthritis. Ankle sprains commonly occur in sports such as basketball, where sudden, lateral changes in direction are common. As a shoe provides the foundational support for an athlete, a simple slipping/tipping analysis was performed to derive a stability criterion that relates impact forces and shoe geometry. The criterion was populated with geometric measurements from seven currently-available basketball shoes and impact forces seen in lateral maneuvers from several published studies to generate multiple cases to observe if the shoes were safe. Of the 35 cases (seven different shoes applied in six different loading conditions) there were six cases where the shoe passed the stability criterion and was considered safe. Given that the impact forces in lateral movements likely will not change, the geometry of the shoes should be considered to reduce the chance of tipping of the shoe (i.e. rolling of the ankle) and risk of injury to the athlete.</p><p>Another contributing factor to the healthcare system's economic burden is limb loss, and the negative effects of ill-fitting and ill-functioning prosthetic devices. Examples of these secondary complications are osteoarthritis and tissue breakdown, which are thought to result from uneven joint loading and asymmetric gait. In light of this, a prosthetic ankle was developed that employs a three degree of freedom system modeled with a ball-in-socket joint. The range of motion of this joint can be custom-bounded by the system of nubs and cavities, along with shims that can be inserted around the joint shaft, to control dorsiflexion, plantarflexion, inversion, eversion, and medial/lateral rotation in the transverse plane. A joint like this, which enables the user to have a more natural gait, will help reduce the onset of conditions like osteoarthritis, ultimately reducing the demand on resources from the healthcare system.</p><p>Another effort to mitigate the burden on the healthcare system is seen through the development of a wearable resistance device that is designed to help prevent injury by strengthening musculoskeletal and neuromuscular systems during sport-specific movements. While traditional gym training is beneficial for an athlete's overall health and fitness, it tends to lack in adequately preparing the athlete for sport-specific movements. Thus, a wearable resistance system is beneficial in that it can provide resistance training during sport to enhance and strengthen an athlete's neuromuscular and musculoskeletal systems. In this study, five recreational runners performed running trials on an instrumented treadmill with and without the wearable resistance system. Force plate and surface electromyography (sEMG) data were collected to observe changes in the muscle activation in both legs. Additionally, sEMG data was examined to detect any effect on left/right symmetry in each subject. </p><p>These studies can all be enhanced with the incorporation of a newly-developed skeletal muscle force model that provides more accurate estimates of individualized muscle forces to better predict surrounding musculoskeletal tissue and joint contact loading. It is founded in dimensional analysis and uses electromyography and the muscle force-length, force-velocity, and force-frequency curves as inputs. The constitutive equation gives way to a unique application of inverse-dynamics that avoids the issue of indeterminacy when reaction moments and ligament loading are minimized in a joint. The ankle joint is used as an example for developing the equations that culminate into a system of linear equations. Seventeen subjects (8 males, 9 females) performed five different exercises geared towards activating the primary muscles crossing the ankle joint. The moments about the ankle joint due to the calculated muscle forces were compared to the sum of the moments due to all other sources and the kinematic terms in the second Newton-Euler equation of rigid body motion. Average percent errors for the \(\vec{B}\) components for each subject ranged from 4.2\% to 15.5\% with a total average percent error across all subjects of 8.2\%. Not only is this muscle force model physiologically relevant, but it can be calibrated and used to predict joint contact loading and loading in the surrounding tissues. Thus, it will be beneficial for use in designing biomechanics equipment for athletes like basketball players, or in designing prosthetic devices that function more like a natural joint. Furthermore, this model can be used in conjunction with the wearable resistance device to validate it's effects on the strengthening of neuromuscular and musculoskeletal systems over time.</p>