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A better understanding of structural and functional interactions between cardiac and non-cardiac cells is essential to better address the sequelae of cardiac disease and improve the potential cellular implantation therapies. First, an in vitro model was established to investigate the probability that electromechanical junctions form between cardiac and non-cardiac cells. Soft lithography techniques were used to create abutting-trapezoid shaped protein islands that supported the formation of isolated cell pairs with a defined cell-cell contact interface. After assessing connexin 43 and N-cadherin expression, higher chances for functional coupling with host cardiomyocytes exist for mesenchymal stem cells (MSC), followed by skeletal myoblasts (SKM), and finally cardiac fibroblasts (CF). Second, we studied the effect resulting from factors secreted by (1) donor cells (SKMs or MSCs) and (2) cardiac fibroblasts on the electrophysiological properties (EP) of 2-D cardiac networks in vitro. Specifically, we conditioned a defined serum-free media (control media) for 24 hours in the presence of non-cardiac cells and assessed electrophysiological properties. Our results indicate that (1) that paracrine factors secreted by cardiac fibroblasts could contribute to the progression of fibrotic cardiac disease, (2) that there may be a crosstalk mechanism between CFs and cardiomyocytes that prevents this paracrine action to occur in a healthy heart, which could be exploited for possible future cardiac therapies, and finally (3) that protection of cardiomyocytes from the negative paracrine action of CFs in a post-infarcted heart may be another possible mechanism of how donor cells used in cardiomyoplasty improve cardiac function without cellular engraftment. In summary, this research represents one of the steps towards the ultimate design of safe and effective therapies for the restoration of heart function after myocardial infarction. / Dissertation

<p>Cortical brain-machine interface (BMI) systems as they currently exist within the research environment are not suitable for general clinical use. A clinical system must be fully implantable, requiring no chronic breaks in the skin. This work addresses the communication and processing needs of a fully implantable neural data acquisition system. Such a system is a key component of a clinically viable BMI. This work primarily focuses on the design, implementation, and testing of a data reduction scheme for 96 channels of neural data and a bidirectional telemetry link for sending data out of the body and providing commands and configuration information to the implanted portion of the system.</p><p>The data reduction scheme and an interface to a one megabit per second commercial transceiver were implemented in a single programmable logic device. The data reduction scheme makes use of a voltage thresholding spike detection technique. The threshold for each channel is computed automatically based on a user-defined multiplier and an estimate of the noise level. The interface to the transceiver performs all necessary serial encoding and decoding, queuing, and packet assembly and disassembly.</p><p>The data reduction portion of the system was tested using simulated neural signals. Spike detection performance was evaluated using thirty different multiplier values over a wide range of signal-to-noise ratios. Spike extraction tests showed that the system could output up to 2000 extracted spikes per second with latencies suitable for a BMI application. The circumstances under which some spikes would not be transmitted by the system were also characterized. Finally, an investigation of automatic threshold selection methods suitable for a BMI application was conducted. The results suggest that the spike detection technique used in the data reduction scheme is appropriate for this application.</p><p>The neural data acquisition system has been fully implanted in several sheep and has successfully recorded, processed, and transmitted neural data during these experiments. The system is also shown to interface well with commercial spike sorting software and with all of the necessary components of a BMI setup, demonstrating suitability for integration into systems that have already been shown to be effective in the laboratory environment.</p> / Dissertation

<p>Lung disease is the third most common cause of death in the United States, resulting in 400,000 deaths annually \cite{ALA:08}. For many diseases, lung transplantation is the only definitive treatment, yet only 2700 lung transplants are performed each year, limited primarily by a lack of donor organs \cite{Christie:09}. The development of engineered lung tissue, which could be created using a patient's own cells, could have a significant impact on the treatment of end-stage lung disease.</p><p>In this dissertation, we describe the first work intended to engineer whole lung tissue. We utilize a decellularized rodent lung scaffold that is then seeded with pulmonary cells in order to create engineered lung tissue. We will first describe the production of a decellularized lung matrix, which retains several key characteristics of normal lung matrix and is superior to other matrix options for lung tissue engineering. We will analyze the mechanical integrity of the scaffolds and compare the collagen, elastin, fibronectin, and proteoglycan content of the scaffolds to native tissue. We also use a variety of imaging modalities to study the architecture, microstructure and ultrastructure of the scaffolds.</p><p>We will then document the design and validation of a bioreactor that is capable of the long-term culture of whole lung tissue in the laboratory. To validate the bioreactor design, we culture native lung tissue for up to 7 days and demonstrate that the bioreactor enables the maintenance of cell viability, cellular differentiation state, and lung morphology.</p><p>We then demonstrate that the decellularized scaffolds, when cultured in the bioreactor with a suitable cell source, can support the adherence and proliferation of a wide range of cell types, including pulmonary endothelial, epithelial, and mesenchymal cells. We examine the effects of bioreactor conditions, including medium type, ventilation and perfusion, and an air-liquid interface, on the growth and differentiation of epithelial and endothelial lung tissue. Finally, we evaluate several key functional aspects of the engineered tissues, including surfactant production and the formation of a barrier between the vascular and airway compartments.</p><p>In summary, this work demonstrates the development of tools, techniques and platforms for the growth of engineered lung tissues, and provides a foundation for the continued development of whole, functional engineered lung tissue.</p> / Dissertation

Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2009. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3635. Adviser: William D. O'Brien. Includes bibliographical references (leaves 129-144) Available on microfilm from Pro Quest Information and Learning.

Thesis (Ph.D.)--University of California, San Francisco with the University of California, Berkeley, 2009. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3639. Adviser: Jeffrey C. Lotz.

Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2009. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3640. Adviser: Brian T. Cunningham. Includes bibliographical references. Available on microfilm from Pro Quest Information and Learning.

Calcium phosphate ceramic (CPC) coated strain gauges have been used for long term in vivo bone strain measurements but require 6 to 9 weeks for sufficient bonding. PepTite2000™, OP-1, TGF-β1, Ca₂SO₄·2H₂O, and an endothelial cell layer with and without TGF-β1 were examined as enhancements to accelerate bone to CPC bonding. Young male Sprague-Dawley rats were implanted with gauges for three weeks and calcein labeled. Following euthanasia, their femurs were explanted and mechanically tested. Histology was completed. Optical Coherence Tomography (OCT) was studied as an alternative to histology. A finite element analysis (FEA) examined bone to gauge strain transfer. Mechanical testing indicated increased sensing accuracy with TGF-β1 and OP-1 enhancements versus unenhanced gauges. PepTite2000™ and endothelial enhanced gauges displayed lower sensing accuracy and contained vasculature near CPC. TGF-β1 increased bonding with endothelial cells. Ca₂SO₄·2H₂O inhibited bone bonding. OCT unsuccessfully imaged bone to CPC contact. FEA identified geometric and material parameters for improved gauge design.