Coronary artery stent placement has been a significant advance in the percutaneous treatment of atherosclerotic disease, and tissue engineered vascular grafts may provide a viable alternative to autologous segments for small diameter vessels. However, in-stent restenosis remains an important limitation, and tissue engineered grafts have poor patency and high risk of thrombus formation due to their inability to maintain a confluent, adherent, and quiescent endothelium. While animal models provide insight into the pathophysiology of these situations, elucidation of the relative importance of stent or graft components, hemodynamic factors, and molecular factors is difficult. Very little research has focused on bridging gaps in knowledge concerning blood/biomaterial interactions, blood/endothelial cell interactions, and endothelial cell/smooth muscle cell cross-talk. The work presented within this thesis will do just that. The objective of this thesis research was to elucidate the influence of biomaterial-induced activation of leukocytes on endothelial cell or smooth muscle cell phenotype, as well as endothelial cell/smooth muscle cell cross-talk in co-culture systems. Towards this goal, two complimentary in vitro endothelial cell/smooth muscle cell co-culture models with divergent smooth muscle cell phenotype were developed and characterized. Using these systems, it was found that the presence of more secretory smooth muscle cells (as would be seen in wound healing or disease) in general enhanced endothelial cell activation in response to biomaterial-pretreated monocytes, while the presence of less secretory smooth muscle cells (to model more quiescent smooth muscle cells found in uninjured healthy vessels) suppressed endothelial cell activation in response to biomaterial-pretreated monocytes (and neutrophils to a small degree). Additionally, biomaterial-pretreated monocytes and neutrophils amplified a smooth muscle cell phenotypic shift away from a more quiescent state. It is likely that the compounding effect of secretory smooth muscle cells and biomaterial-activated leukocytes are responsible for altered vascular wound healing upon implantation of stents or vascular grafts. Understanding the specific signals causing these effects, or signals delivered by contractile smooth muscle cells that limit these effects help to provide design criteria for development of devices or grafts capable of long term patency.

The field of structural design optimization is one with great breadth and depth in many engineering applications. From the perspective of a designer, three distinct numerical methodologies may be employed. These include size, shape, and topology optimization, in which the ordering typically (but not always) corresponds to the order of increasing complexity and computational expense. This, of course, depends on the particular problem of interest and the selected numerical methods. The primary focus of this research employs density-based topology optimization with the goal of improving structural resistance to failure. Beginning with brittle fracture, two topology optimization based formulations are proposed in which low weight designs are achieved with substantially increased fracture resistance. In contrast to the majority of the current relevant literature which favors stress constraints with linear elastic physics, we explicitly simulate brittle fracture using the phase field method during the topology optimization procedure. In the second formulation, a direct comparison is made against results obtained using conventional stress-constrained topology optimization and the improved performance is numerically demonstrated. Multiple enhancements are proposed including a numerical efficiency gain based on the Schur-complement during the analytical sensitivity analysis and a new function which provides additional path information to the optimizer, making the gradient-based optimization problem more tractable in the presence of brittle fracture physics. Subsequently, design for ductile failure and buckling resistance is addressed and a numerically efficient topology optimization formulation is proposed which may provide significant design improvements when ductile materials are used and extreme loading situations are anticipated. The proposed scheme is examined regarding its impact on both the peak load carrying capacity of the structure and the amount of external work required to achieve this peak load, past which the structure may no longer be able to support any increase in the external force. The optimized structures are also subjected to a post-optimization verification step in which a large deformation phase field fracture model is used to numerically compare the performance of each design. Significant gains in structural strength and toughness are demonstrated using the proposed framework. Additionally, the failure behavior of 3D-printed polymer composites is investigated, both numerically and experimentally. A large deformation phase field fracture model is derived under the assumption of plane-stress for numerical efficiency. Experimental results are compared to numerical simulations for a composite system consisting of three stiff circular inclusions embedded into a soft matrix. In particular, we examine how geometric parameters, such as the distances between inclusions and the length of initial notches affect the failure pattern in the soft composites. It is shown that the mechanical performance of the system (e.g. strength and toughness) can be tuned through selection of the inclusion positions which offers useful insight for material design. Finally, a size optimization technique for a cardiovascular stent is proposed with application to a balloon expandable prosthetic heart valve intended for the pediatric population born with Congenital Heart Disease (CHD). Multiple open heart surgical procedures are typically required in order to replace the original diseased valve and subsequent prosthetic valves with those of larger diameter as the patient grows. Most expandable prosthetic heart valves currently in development to resolve this issue do not incorporate a corresponding expandable conduit that is typically required in a neonate without a sufficiently long Right Ventricular Outflow Tract (RVOT). Within the context of a particular design, a numerical methodology is proposed for designing a metallic stent incorporated into the conduit between layers of polymeric glue. A multiobjective optimization problem is solved, not only to resist the retractive forces of the glue layers, but also to ensure the durability of the stent both during expansion and while subject to the anticipated high cycle fatigue loading. It is demonstrated that the surrogate-based optimization strategy is effective for understanding the trade-offs between each performance metric and ultimately efficiently arriving at a single optimized design candidate. Finally, it is shown that the desired expandability of the device from 12mm to 16mm inner diameter is achievable, effectively eliminating at least one open heart surgical procedure for certain children born with CHD.

High entropy alloys (HEAs) are alloys with five or more principal elements. Due to these distinct concept of alloying, the HEA exhibits unique and superior properties. The outstanding properties of HEA includes higher strength/hardness, superior wear resistance, high temperature stability, higher fatigue life, good corrosion and oxidation resistance. Such characteristics of HEA has been significant interest leading to researches on these emerging field. Even though many works are done to understand the characteristic of these HEAs, very few works are made on how the HEAs can be applied for commercial uses. This work discusses the application of High entropy alloys in biomedical applications. The coronary heart disease, the leading cause of death in the United States kills more than 350,000 persons/year and it costs $108.9 billion for the nation each year in spite of significant advancements in medical care and public awareness. A cardiovascular disease affects heart or blood vessels (arteries, veins and capillaries) or both by blocking the blood flow. As a surgical interventions, stent implants are deployed to cure or ameliorate the disease. However, the high failure rate of stents has lead researchers to give special attention towards analyzing stent structure, materials and characteristics. Many works related to alternate material and/or design are carried out in recent time. This paper discusses the feasibility of CoCrFeNiMn and Al0.1CoCrFeNi HEAs in stent implant application. This work is based on the speculation that CoCrFeNiMn and Al0.1CoCrFeNi HEAs are biocompatible material. These HEAs are characterized to determine the microstructure and mechanical properties. Computational modeling and analysis were carried out on stent implant by applying CoCrFeNiMn and Al0.1CoCrFeNi HEAs as material to understand the structural behavior.

The coronary heart disease kills more than 350,000 persons/year and it costs $108.9 billion for the United States each year, in spite of significant advancements in clinical care and education for public, cardiovascular diseases (CVD) are leading cause of death and disability to the nation. A cardiovascular disease involves mainly heart or blood vessels (arteries, veins and capillaries) or both, and then mainly occurs in selected regions and affects heart, brain, kidney and peripheral arteries. As a surgical interventions, stent implantation is deployed to cure or ameliorate the disease. However, the high failure rate of stents used in patients with peripheral artery diseases has lead researchers to give special attention towards analyzing stent structure and characteristics. In this research, the mechanical properties of a stent based on the rhombus structure were analyzed and verified by means of analytical and numerical approaches. Theoretical model based on the beam theory were developed and numerical models were used to analyze the response of these structures under various and complex loading conditions. Moreover, the analysis of the stent inflation involves a model with large deformations and large strains, nonlinear material properties need to be considered to accurately capture the deformation process. The maximum stress values were found to occur in localized regions of the stent. These regions were generally found along the inner radii of each of the connected links connecting each of the longitudinal struts. Stress values throughout the whole stent were typically much lower. The peak engineering stress values were found to be less than the material ultimate strength (limit stress 515Mpa), indicating a safe stent design throughout expansion range. Lastly, the rheological behavior of blood can be quantified by non-Newtonian viscosity. Carreau model is introduced and simulates the situation in the artery, then the available shear stress in the model would help to the future analysis in the contact analysis of stent and the artery.