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Cleveland, OH, United States

Gurkan U.A.,Case Western Reserve University | Gurkan U.A.,Advanced Platform Technology Center | El Assal R.,Harvard University | Yildiz S.E.,Harvard University | And 5 more authors.
Molecular Pharmaceutics | Year: 2014

Over the past decade, bioprinting has emerged as a promising patterning strategy to organize cells and extracellular components both in two and three dimensions (2D and 3D) to engineer functional tissue mimicking constructs. So far, tissue printing has neither been used for 3D patterning of mesenchymal stem cells (MSCs) in multiphase growth factor embedded 3D hydrogels nor been investigated phenotypically in terms of simultaneous differentiation into different cell types within the same micropatterned 3D tissue constructs. Accordingly, we demonstrated a biochemical gradient by bioprinting nanoliter droplets encapsulating human MSCs, bone morphogenetic protein 2 (BMP-2), and transforming growth factor β1 (TGF- β1), engineering an anisotropic biomimetic fibrocartilage microenvironment. Assessment of the model tissue construct displayed multiphasic anisotropy of the incorporated biochemical factors after patterning. Quantitative real time polymerase chain reaction (qRT-PCR) results suggested genomic expression patterns leading to simultaneous differentiation of MSC populations into osteogenic and chondrogenic phenotype within the multiphasic construct, evidenced by upregulation of osteogenesis and condrogenesis related genes during in vitro culture. Comprehensive phenotypic network and pathway analysis results, which were based on genomic expression data, indicated activation of differentiation related mechanisms, via signaling pathways, including TGF, BMP, and vascular endothelial growth factor. © 2014 American Chemical Society.

Potkay J.A.,Advanced Platform Technology Center | Wise K.D.,University of Michigan
Micromachines | Year: 2012

This paper presents a low-power hybrid thermopneumatic microvalve with an electrostatic hold and integrated valve plate position sensing. This combination of actuators in a single structure enables a high throw and force actuator with low energy consumption, a combination that is difficult to otherwise achieve. The completed 7.5 mm × 10.3 mm × 1.5 mm valve has an open flow rate of 8 sccm at 600 Pa, a leak rate of 2.2 × 10-3 sccm at 115 kPa, a open-to-closed fluidic conductance ratio of nearly one million, an actuation time of 430 ms at 250 mW, and a required power of 90 mW while closed. It additionally requires no power to open, and has a built-in capacitive position sensor with a sensitivity of 9.8 fF/kPa. The paper additionally presents analytical models of the valve components, design tradeoffs, and guidelines for achieving an optimized device. © 2012 by the authors.

Azin M.,Case Western Reserve University | Guggenmos D.J.,University of Kansas | Barbay S.,University of Kansas | Nudo R.J.,University of Kansas | And 2 more authors.
IEEE Journal of Solid-State Circuits | Year: 2011

This paper describes an activity-dependent intracortical microstimulation (ICMS) system-on-chip (SoC) that converts extracellular neural spikes recorded from one brain region to electrical stimuli delivered to another brain region in real time in vivo. The 10.9-mm2 SoC incorporates two identical 4-channel modules, each comprising an analog recording front-end with total input noise voltage of 3.12 μVrms and noise efficiency factor (NEF) of 2.68, 5.9-μW 10-bit successive approximation register analog-to-digital converters (SAR ADCs), 12.4-μW digital spike discrimination processor, and a programmable constant-current microstimulating back-end that delivers up to 94.5 μA with 6-bit resolution to stimulate the cortical tissue when triggered by neural activity. For autonomous operation, the SoC also integrates biasing and clock generation circuitry, frequency-shift-keyed (FSK) transmitter at 433 MHz, and dc-dc converter that generates a power supply of 5.05 V for the microstimulating back-end from a single 1.5-V battery. Measured results from electrical performance characterization and biological experiments with anesthetized rats are presented from a prototype chip fabricated in AMS 0.35 μm two-poly four-metal (2P/4M) CMOS. A noise analysis for the selected low-noise amplifier (LNA) topology is presented that obtains a minimum NEF of 2.33 for a practical design given the technology parameters and power supply voltage. Future considerations in the SoC design with respect to silicon area and power consumption when increasing the number of channels are also discussed. © 2006 IEEE.

Goldman H.B.,Cleveland Clinic | Sievert K.-D.,University of Tubingen | Damaser M.S.,Cleveland Clinic | Damaser M.S.,Advanced Platform Technology Center
Neurourology and Urodynamics | Year: 2012

Aims To review the current state of research in the use of stem cells (SCs) for stress urinary incontinence (SUI) and assess the likelihood of this becoming a relevant treatment option. Methods The peer-reviewed literature consisting of relevant clinical and animal studies on the topic of SUI was surveyed and reviewed. Results Animal studies have demonstrated the potential utility of SCs in promoting functional recovery of the urethra after simulated childbirth injury. Research in animals suggests similar urethral recovery after injection of bone marrow derived mesenchymal SC secretions as after injection of the SCs themselves. Therefore, whether the improvements result from the injection of the SCs themselves or from their secretion of specific proteins is unclear. Early clinical trials have demonstrated the feasibility and short-term safety of injecting muscle-derived SCs into the urethra to treat SUI. Conclusions Larger and longer-term clinical trials are needed. Nonetheless, efficacious SC-based therapy for the treatment of SUI is practical, achievable and should be available as a treatment modality in the near future. Copyright © 2012 Wiley Periodicals, Inc.

Potkay J.A.,Case Western Reserve University | Potkay J.A.,Advanced Platform Technology Center
Biomedical Microdevices | Year: 2013

Microfabrication techniques are attractive for constructing artificial lungs due to the ability to create features similar in size to those in the natural lung. However, a simple and intuitive mathematical model capable of accurately predicting the gas exchange performance of microchannel artificial lungs does not currently exist. Such a model is critical to understanding and optimizing these devices. Here, we describe a simple, closed-form mathematical model for gas exchange in microchannel artificial lungs and qualify it through application to experimental data from several research groups. We utilize lumped parameters and several assumptions to obtain a closed-form set of equations that describe gas exchange. This work is intended to augment computational models by providing a more intuitive, albeit potentially less accurate, understanding of the operation and trade-offs inherent in microchannel artificial lung devices. © 2013 © Springer Science+Business Media New York (outside the USA).

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