Prevascularized, Co-Culture Model for Breast Cancer Drug Development

The objective of this study was to create 3D engineered tissue models to accelerate identification of safe and efficacious breast cancer drug therapies. It is expected that this platform will dramatically reduce the time and costs associated with development and regulatory approval of anti-cancer therapies, currently a multi-billion dollar endeavor [1]. Existing two-dimensional (2D) in vitro and in vivo animal studies required for identification of effective cancer therapies account for much of the high costs of anti-cancer medications and health insurance premiums borne by patients, many of whom cannot afford it. An emerging paradigm in pharmaceutical drug development is the use of three-dimensional (3D) cell/biomaterial models that will accurately screen novel therapeutic compounds, repurpose existing compounds and terminate ineffective ones. In particular, identification of effective chemotherapies for breast cancer are anticipated to occur more quickly in 3D in vitro models than 2D in vitro environments and in vivo animal models, neither of which accurately mimic natural human tumor environments [2]. Moreover, these 3D models can be multi-cellular and designed with extracellular matrix (ECM) function and mechanical properties similar to that of natural in vivo cancer environments [3].

Design and Marker-Based Validation of a Biplane Fluoroscopy System for Studying the Foot and Ankle

The ability to accurately measure three dimensional (3D) bone kinematics is key to understanding the motion of the joints of the body, and how such motion is altered by injury, disease, and treatment. Precise measurement of such kinematics is technically challenging. Biplane fluoroscopy is ideally suited to measure bone motion. Such systems have been developed in the past for both radiographic stereo-photogrammetric analysis (RSA) [1] and the more challenging model-based analysis [2]. Research groups have studied the knee [3,4], shoulder [5] and ankle [6] motion with similar techniques. The work presented here is an initial evaluation of the performance of our system, i.e., a validation that this in-house system can detect magnitudes of motion on-par with other existing systems.

A New Generation of Aortic Valve Prosthesis: Design, Manufacture and Hydrodynamic Assessment

Aortic valve replacement (AVR) is the second most common cardiac procedure after coronary artery bypass grafting, accounting for more than 200,000 transplantations annually worldwide [1]. Currently available mechanical and bioprosthetic heart valve replacements are not ideal as they are associated with relevant complications. The tri-leaflet polymeric heart valves (PHVs) have been widely investigated as possible alternative to these substitutes. However, the clinical application of PHVs has been limited by their suboptimal design and poor durability of available polymeric materials. This study presents a new concept of surgical aortic valve using a novel nanocomposite polymer.

Quantitative Studies of Fibronectin Adsorption on Submicron Scaffolds

Fibronectin plays a crucial role in adhesion of several cell types, mainly due to the fact that it is recognized by at least ten different integrin receptors. Since most cell types can bind to fibronectin, it becomes involved in many various biological processes. The interaction of cells with ECM proteins such as fibronectin provides the signals affecting morphology, motility, gene expression, and survival of cells [1]. Fibronectin exists in both soluble and insoluble forms; soluble fibronectin is secreted by cells and exits in cell media or body fluids, whereas insoluble fibronectin exists in tissues or the extracellular matrix of cultured cells [2]. The ability to control adsorption of fibronectin on tissue engineering scaffolds would therefore play a huge role in controlling cell attachment and survival in vivo. This can be achieved through surface functionalization of the scaffolds. The goal of these studies is to use molecular dynamics (MD) simulations to mechanistically understand how fibronectin adsorption is enhanced by surface functionalization of submicron scaffolds.

Surgeon Perception of Cancellous Screw Fixation

The ability of surgeons to optimize screw insertion torque in nonlocking fixation constructs is important for stability, particularly in osteoporotic and cancellous bone. This study evaluated screw torque applied by surgeons during simulated cancellous fixation. It evaluated the frequency that synthetic cancellous bone were stripped by the surgeon, factors associated with bone stripping, and the ability of surgeons to recognize it.

Finite Element Based Injury Metrics for Pulmonary Contusion From Vehicle to Vehicle Crash Simulations

Motor Vehicle Crashes (MVCs) are a public health problem in the United States. In 2009, 33,808 Americans were killed in a MVC and 2.22 million more were injured.4 Pulmonary contusion (PC) is a common injury following MVC with over 38% of the Abbreviated Injury Scale (AIS) 3+ thoracic injuries identified as some form of PC in a recent National Automotive Sampling System (NASS) study.5 Miller et al. correlated the percent injured lung to the possibility of developing Acute Respiratory Distress Syndrome (ARDS). The results indicated that if 20% of the lung was injured, the incidence of ARDS sharply increased with seventy-eight percent of those patients developing ARDS.2 The significance of these findings is that the volumetric measurement of PC can predict possible clinical outcomes.

Fluid-Structure Interaction Simulation of the Edge-to-Edge Repair of the Mitral Valve in Functional and Degenerative States

The most common dysfunction of the mitral valve (MV) is mitral valve regurgitation (MVR) which accounts for approximately 70% of native MV dysfunction [1]. During closure, abnormal amounts of retrograde flow enter the left atrium altering ventricular haemodynamics, an issue which can lead to cardiac related pathologies. MVR is caused by a variety of different mechanisms which are either degenerative (myxomatous degeneration) or functional (annular dilation or papillary muscle displacement) [2]. Correction of MVR is performed by repairing existing valve anatomy or replacement with a prosthetic substitute, however repair is preferred as mortality rates are reduced (2.0% against 6.1% for replacement) along with other valve related complications [3]. A common and popular method of repair is the edge-to-edge repair (ETER), which aims to correct MVR by surgically connecting the regurgitant region through reducing the inter-leaflet distance. Although MV function is improved in systole, induced stresses are significantly increased in diastole where the MV is typically in a low state of stress. In order to assess the effect of this technique in diastole, where the dynamics of both the MV and ventricular filling are disrupted it is required to use fluid-structure interaction (FSI) modelling techniques. Here a FSI model of the of the MV has been described, using this model the resulting induced stresses from the ETER in both functional and degenerative states of the MV have been simulated and assessed using the explicit finite element code LS-DYNA.

Assessment of the Effect of Coronary Occlusion on Aortic Valve Dynamics Using a Global 3D FSI Model

Coronary artery disease (CAD) is considered to be a major cause of mortality and morbidity in the developing world. It has recently been shown that aortic root pathologies such as aortic stiffening and calcific aortic stenosis can contribute to the initiation and progression of this disease by affecting coronary blood flow [1,2]. Such pathologies influence the distensibility of the aortic root and therefore the hemodynamics of the entire region. As a consequence the coronary blood flow and velocity profiles will be altered [3,4,5] which could accelerate the development of an existing coronary artery disease. However, it would be very interesting to see if an occluded coronary artery would have a mutual impact on valvular dynamics and aortic root pathologies. This bi-directionality could aggravate and contribute to the progression of both the coronary and aortic root pathology.

Pure Moment Testing for Spinal Biomechanics Applications: Fixed Versus 3D Floating Ring Cable-Driven Test Designs

For spine biomechanical tests, the cable-driven system in particular has been widely used to apply pure bending moments. The advantages to pure moment testing lie in its consistency as an accepted standard protocol across previous literature and its ability to ensure uniform loading across all levels of the spinal column. Of the methods used for pure moment testing, cable-driven set-ups are popular due to their low requirements and simple design. Crawford et al [1] were the first to employ this method, but prior work by our group indicated a discrepancy between applied and intended moment for this system in flexion-extension only [2]. We hypothesize that this discrepancy can be observed in other bending modes and minimized with a second-generation floating ring design to eliminate off-axis loads.

Surgical Variability of Resection Parameters During Total Knee Arthroplasty

There is intrinsic surgical variability in the practice of total knee arthroplasty (TKA), and thus computational analyses of TKA should account for this variability to ensure clinical applicability and robustness of results. Statistical inputs within computational analyses have been used to assess the biomechanical characteristics of TKA implants [1], and such methodologies are promising when applied to morphological analysis of TKA in order to motivate component design, assess current designs, and improve the understanding of surgical outcomes. Analyses to date either directly use actual TKA component placement or bone resection data [2], or assume a single set of parameters for placement and resection across the entire specimen group that was investigated [3], and thus do not account for surgical variability. This could be due to a lack of available data to quantify clinical variability in TKA component placement.