Human red blood cells (RBCs) must undergo severe deformation to pass through narrow capillaries and submicronic splenic slits for several hundred thousand times in their normal lifespan. Studies of RBC biomechanics have been mainly focused on cell deformability measured from a single application of stress using classical biomechanical techniques, such as optical tweezers and micropipette aspiration. Mechanical fatigue effect on RBCs under cyclic loadings of stress that contributes to the membrane failure in blood circulation is not fully understood. This research developed a new experimental method for mechanical fatigue testing of RBCs using amplitude-modulated electro-deformation technique. Biomechanical parameters of individually tracked RBCs show strong correlations with the number of the loading cycles. Effects of loading configurations on the cellular fatigue behavior of RBCs is further studied. The results uniquely establish the important role of mechanical fatigue in influencing physical properties of biological cells. They further provide insights into the accumulated membrane damage during blood circulation, paving the way for further investigations of the eventual failure of RBCs in various hemolytic pathologies. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2019. / FAU Electronic Theses and Dissertations Collection

The transition from cycling to running has been identified as one of the key determinants of success in triathlon, as it has been suggested that the cycle may affect subsequent running efficiency such that running performance is significantly altered or reduced. It is also suggested that athletes more adapted to the transition itself, rather than purely running or cycling, may be more efficient during the post-cycle running bout. The current study sought to investigate the effects of prior cycling on subsequent selected biomechanical, physiological and perceptual responses of three different athlete groups. Subjects were selected on the basis of their sporting background, and were divided into three groups – triathletes, cyclists and runners. Experimentation required subjects to perform a seven minute treadmill running protocol at 15km.h⁻¹, during which biomechanical (EMG, Stride rate, Stride length, Vertical acceleration), physiological (HR, VO₂, EE) and perceptual (RPE) responses were recorded. After resting, subjects were required to perform a twenty minute stationary cycle at 70% of maximal aerobic power (previously determined), immediately followed by a second seven minute treadmill running protocol during which the same data were collected and compared to those collected during the first run. Biomechanical responses indicate that the cycle protocol had no effect on the muscle activity or vertical acceleration responses of any of the three subject groups, while the triathlete group significantly altered their gait responses in order to preserve running economy. The triathlete group was the least affected when considering the physiological responses, as running economy was preserved for this group. The runner and cyclist groups were significantly affected by the transition, as running economy decreased significantly for these groups. Perceptual responses indicate that athletes more experienced with the transition may find the transition from cycling to running to be easier than those inexperienced in this transition. It is apparent that a high intensity cycle protocol has limited statistical impact on selected biomechanical responses, while physiological and perceptual responses were altered, during a subsequent run, regardless of athlete type. That said, the ability of transition-trained athletes to transition comfortably between disciplines was highlighted, which may have important performance implications.

Indiana University-Purdue University Indianapolis (IUPUI) / Signal Transducer and Activator of Transcription 3 (Stat3) is a transcription factor expressed in bone and joint cells that include osteoblasts, osteocytes, osteoclasts, and chondrocytes. Stat3 is activated by a variety of cytokines and growth factors, including IL-6/gp130 family cytokines. These cytokines not only regulate the differentiation of osteoblasts and osteoclasts, but also regulate proliferation of chondrocytes through Stat3 activation. In 2007, mutations of Stat3 have been confirmed to cause a rare human immunodeficiency disease – Job syndrome which presents skeletal abnormalities like: reduced bone density (osteopenia), scoliosis, hyperextensibility of joints, and recurrent pathological bone fractures. Changes in the Stat3 gene alter the structure and function of the Stat3 proteins, impairing its ability to control the activity of other genes. However, little is known about the effects of Stat3 mutations on bone cells and tissues. To investigate the in vivo physiological role of Stat3 in bone homeostasis, osteoblast/osteocyte-specific Stat3 knockout (KO) mice were generated via the Cre-LoxP recombination system. The osteoblast/osteocyte-specific Stat3 KO mice showed bone abnormalities and an osteoporotic phenotype because of a reduced bone formation rate. Furthermore, inactivation of Stat3 decreased load-driven bone formation, and the disruption of Stat3 in osteoblasts suppressed load-driven mitochondrial activity, which led to an elevated level of reactive oxygen species (ROS) in cultured primary osteoblasts. Stat3 has been found to be responsive to mechanical stimulation, and might play an important role in mechanical signal transduction in osteocytes. To investigate the role Stat3 plays in mechanical signaling transduction, osteocyte-specific Stat3 knockout (KO) mice were created. Inactivation of Stat3 in osteocytes presented a significantly reduced load-driven bone formation. Decreased osteoblast activity indicated by reduced osteoid surface was also found in osteocyte-specific Stat3 KO mice. Moreover, sclerostin (SOST) protein which is a critical osteocyte-specific inhibitor of bone formation, its encoded gene SOST expression has been found to be enhanced in osteocyte-specific Stat3 KO mice. Thus, these results clearly demonstrated that Stat3 plays an important role in bone homeostasis and mechanotransduction, and Stat3 is not only involved in bone-formation-important genes regulation in the nucleus but also in mediation of ROS and oxidative stress in mitochondria.

A recently emerging engineering design approach entails studying the brilliant design solutions found in nature with an aim to develop design strategies that mimic the remarkable efficiency found in biological systems. This novel engineering approach is referred to as bio-inspired design. In this context, the present study quantifies the structure-property relations in bighorn sheep (Ovis canadensis) horn keratin, qualitatively characterizes the effects of a tapered spiral geometry (the same form as in a ram’s horn) on pressure wave and impulse mitigation, describes the stress attenuation capabilities and features of a ram’s head, and compares the structures and mechanical properties of some energy absorbent natural materials. The results and ideas presented herein can be used in the development of lightweight, energy absorbent, bio-inspired material designs. Among the most notable conclusions garnered from this research include: Horn keratin behaves in an anisotropic manner similar to a long fiber composite. Moisture content dominates the material behavior of horn keratin more than anisotropy, age, and stress-state. This makes moisture content the most influential parameter on the mechanical behavior of horn keratin. Tapered geometries mitigate the impulse generated by a stress wave due to the convergent boundary and a continually decreasing cross sectional area such that greater uniaxial stresses and subsequent axial deformation arises. Furthermore, the tapered geometry introduces small shear stresses that further decrease the impulse. Spiral geometries attenuate the impulse generated by a stress wave by the introduction of shear stresses along the length of the spiral. These shear stresses introduce transverse displacements that function to lessen the impulse. When both a taper and spiral geometry are used in a design, their synergistic effects multiplicatively reduce the impulse Tough natural materials have a high porosity, which makes them light-weight, while increasing their compressive energy absorption ability. Biomaterials whose functions include protection and energy absorption feature a multiscale, hierarchical, composite structure. The constituent materials are arranged in such ways to achieve a synergistic effect, where the properties of the composite exceed the properties of its constituents. Biological materials are therefore not confined to the law of mixtures.

Indiana University-Purdue University Indianapolis (IUPUI) / The passive properties of the venous wall are important in the development of venous pathology. Increase in venous pressure due to retrograde flow (reflux) and obstruction of venous flow by intrinsic and extrinsic means are the two possible mechanisms for venous hypertension. Reflux is the prevailing theory in the etiology of venous insufficiency. The objective of this thesis is to quantify the passive biomechanical response and structural remodeling of veins subjected to chronic venous reflux and hypertension. To investigate the effects of venous reflux on venous mechanics, the tricuspid valve was injured chronically in canines by disrupting the chordae tendineae. The conventional inflation-extension protocol in conjunction with intravascular ultrasound (IVUS) was utilized to investigate the passive biomechanical response of both control common iliac veins (from 9 dogs) and common iliac veins subjected to chronic venous reflux and hypertension (from 9 dogs). The change in thickness and constituent composition as a result of chronic venous reflux and hypertension was quantified using multiphoton microscopy (MPM) and histological evaluation. Biomechanical results indicate that the veins stiffened and became less compliant when exposed to eight weeks of chronic venous reflux and hypertension. The mechanical stiffening was found to be a result of a significant increase in wall thickness (p < 0.05) and a significant increase in the collagen to elastin ratio (p < 0.05). After eight weeks of chronic reflux, the circumferential Cauchy stress significantly reduced (p < 0.05) due to wall thickening, but was not restored to control levels. This provided a useful model for development and further analysis of chronic venous insufficiency and assessment of possible intervention strategies.