Differentiation and Distribution of Marrow Stem Cells in Flex-Flow Environments Demonstrate Support of the Valvular Phenotype

For treatment of critical heart valve diseases, prosthetic valves perform fairly well in most adults; however, for pediatric patients, there is the added requirement that the replacement valve grows with the child, thus extremely limiting current treatment options. Tissue engineered heart valves (TEHV), such as those derived from autologous bone marrow stem cells (BMSCs), have the potential to recapitulate native valve architecture and accommodate somatic growth. However, a fundamental pre-cursor in promoting directed integration with native tissues rather than random, uncontrolled growth requires an understanding of BMSC mechanobiological responses to valve-relevant mechanical environments. Here, we report on the responses of human BMSC-seeded polymer constructs to the valve-relevant stress states of: (i) steady flow alone, (ii) cyclic flexure alone, and (iii) the combination of cyclic flexure and steady flow (flex-flow). BMSCs were seeded onto a PGA: PLLA polymer scaffold and cultured in static culture for 8 days. Subsequently, the aforementioned mechanical conditions, (groups consisting of steady flow alone-850ml/min, cyclic flexure alone-1 Hz, and flex-flow-850ml/min and 1 Hz) were applied for an additional two weeks. We found samples from the flex-flow group exhibited a valve-like distribution of cells that expressed endothelial (preference to the surfaces) and myofibroblast (preference to the intermediate region) phenotypes. We interpret that this was likely due to the presence of both appreciable fluid-induced shear stress magnitudes and oscillatory shear stresses, which were concomitantly imparted onto the samples. These results indicate that flex-flow mechanical environments support directed in vitro differentiation of BMSCs uniquely towards a heart valve phenotype, as evident by cellular distribution and expression of specific gene markers. A priori guidance of BMSC-derived, engineered tissue growth under flex-flow conditions may serve to subsequently promote controlled, engineered to native tissue integration processes in vivo necessary for successful long-term valve remodeling

De novo valve tissue morphology following bioscaffold mitral valve replacement in a juvenile non-human primate model

The utility of implanting a bioscaffold mitral valve consisting of porcine small intestinal submucosa (PSIS) in a juvenile baboon model (12 to 14 months old at the time of implant; n = 3) to assess their in vivo tissue remodeling responses was investigated. Our findings demonstrated that the PSIS mitral valve exhibited the robust presence of de novo extracellular matrix (ECM) at all explantation time points (at 3-, 11-, and 20-months). Apart from a significantly lower level of proteoglycans in the implanted valve’s annulus region (p \u3c 0.05) at 3 months compared to the 11-and 20-month explants, there were no other significant differences (p \u3e 0.05) found between any of the other principal valve ECM components (collagen and elastin) at the leaflet, annulus, or chordae tendinea locations, across these time points. In particular, neochordae tissue had formed, which seamlessly integrated with the native papillary muscles. However, additional processing will be required to trigger accelerated, uniform and complete valve ECM formation in the recipient. Regardless of the specific processing done to the bioscaffold valve, in this proof-of-concept study, we estimate that a 3-month window following bioscaffold valve replacement is the timeline in which complete regeneration of the valve and integration with the host needs to occur

Inferring Pathway Activity toward Precise Disease Classification

The advent of microarray technology has made it possible to classify disease states based on gene expression profiles of patients. Typically, marker genes are selected by measuring the power of their expression profiles to discriminate among patients of different disease states. However, expression-based classification can be challenging in complex diseases due to factors such as cellular heterogeneity within a tissue sample and genetic heterogeneity across patients. A promising technique for coping with these challenges is to incorporate pathway information into the disease classification procedure in order to classify disease based on the activity of entire signaling pathways or protein complexes rather than on the expression levels of individual genes or proteins. We propose a new classification method based on pathway activities inferred for each patient. For each pathway, an activity level is summarized from the gene expression levels of its condition-responsive genes (CORGs), defined as the subset of genes in the pathway whose combined expression delivers optimal discriminative power for the disease phenotype. We show that classifiers using pathway activity achieve better performance than classifiers based on individual gene expression, for both simple and complex case-control studies including differentiation of perturbed from non-perturbed cells and subtyping of several different kinds of cancer. Moreover, the new method outperforms several previous approaches that use a static (i.e., non-conditional) definition of pathways. Within a pathway, the identified CORGs may facilitate the development of better diagnostic markers and the discovery of core alterations in human disease

ROTATIONAL MOULDING AND KNITTED FABRIC COMPOSITES IN THE DEVELOPMENT OF AN INTERVERTEBRAL DISC PROSTHESIS

Master'sMASTER OF ENGINEERIN

Computational Fluid Modeling of Heart Valves

Healthy heart valves are essential for proper blood circulation. Their role is to ensure unidirectional blood flow in the circulatory system. They consist of different tissue layers and are capable of adapting and remodeling their tissue composition according to the hemodynamic environments surrounding them [1-3]. The mitral and tricuspid valves are located between the atria and ventricles while the pulmonary valve is found intersecting the right ventricle and the pulmonary artery. The aortic valve resides between the left ventricle and the aorta.https://nsuworks.nova.edu/gscis_facbooks/1019/thumbnail.jp

Applicability of the Taguchi Method to Mechanobiology-Based Experiments

Design of experiments (DOE) methods are very commonly used for process validation. In this study, we employed the Taguchi approach in order to develop an optimal process for the maximization of oscillatory shear stress environments (OSS). OSS has been associated with increase in cellular activity and has been linked to healthy gene expression and tissue formation. Therefore, OSS may be a key factor for many tissue-engineering applications. The results obtained through the Taguchi method identified the best combination of factors and levels associated with higher OSS. These conclusions were found to be in agreement with computational fluid dynamics (CFD) results that we previously found concerning optimal experimental set-up for OSS maximization