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.
Majerus S.J.A.,Case Western Reserve University |
Fletter P.C.,Advanced Platform Technology Center |
Damaser M.S.,Advanced Platform Technology Center |
Garverick S.L.,West Wireless Health Institute
IEEE Transactions on Biomedical Engineering | Year: 2011
This letter describes the design, fabrication, and testing of a wireless bladder-pressure-sensing system for chronic, point-of-care applications, such as urodynamics or closed-loop neuromodulation. The system consists of a miniature implantable device and an external RF receiver and wireless battery charger. The implant is small enough to be cystoscopically implanted within the bladder wall, where it is securely held and shielded from the urine stream. The implant consists of a custom application-specific integrated circuit (ASIC), a pressure transducer, a rechargeable battery, and wireless telemetry and recharging antennas. The ASIC includes instrumentation, wireless transmission, and power-management circuitry, and on an average draws less than 9 μA from the 3.6-V battery. The battery charge can be wirelessly replenished with daily 6-h recharge periods that can occur during the periods of sleep. Acute in vivo evaluation of the pressure-sensing system in canine models has demonstrated that the system can accurately capture lumen pressure from a submucosal implant location. © 2006 IEEE.
Potter K.A.,Case Western Reserve University |
Potter K.A.,Advanced Platform Technology Center |
Jorfi M.,University of Fribourg |
Householder K.T.,Case Western Reserve University |
And 5 more authors.
Acta Biomaterialia | Year: 2014
The cellular and molecular mechanisms by which neuroinflammatory pathways respond to and propagate the reactive tissue response to intracortical microelectrodes remain active areas of research. We previously demonstrated that both the mechanical mismatch between rigid implants and the much softer brain tissue, as well as oxidative stress, contribute to the neurodegenerative reactive tissue response to intracortical implants. In this study, we utilize physiologically responsive, mechanically adaptive polymer implants based on poly(vinyl alcohol) (PVA), with the capability to also locally administer the antioxidant curcumin. The goal of this study is to investigate if the combination of two independently effective mechanisms - softening of the implant and antioxidant release - leads to synergistic effects in vivo. Over the first 4 weeks of the implantation, curcumin-releasing, mechanically adaptive implants were associated with higher neuron survival and a more stable blood-brain barrier at the implant-tissue interface than the neat PVA controls. 12 weeks post-implantation, the benefits of the curcumin release were lost, and both sets of compliant materials (with and without curcumin) had no statistically significant differences in neuronal density distribution profiles. Overall, however, the curcumin-releasing softening polymer implants cause minimal implant-mediated neuroinflammation, and embody the new concept of localized drug delivery from mechanically adaptive intracortical implants. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Alapan Y.,Case Western Reserve University |
Little J.A.,Case Western Reserve University |
Little J.A.,Seidman Cancer Center at University Hospitals |
Gurkan U.A.,Case Western Reserve University |
Gurkan U.A.,Advanced Platform Technology Center
Scientific Reports | Year: 2014
We present a microfluidic approach that allows simultaneous interrogation of RBC properties in physiological flow conditions at a single cell level. With this method, we studied healthy hemoglobin A (HbA) and homozygous sickle hemoglobin (HbS) containing RBCs using whole blood samples from twelve subjects. We report that HbS-containing RBCs are heterogeneous in terms of adhesion and deformability in flow.
Wu G.A.,Advanced Platform Technology Center |
Wu G.A.,Case Western Reserve University |
Bogie K.M.,Advanced Platform Technology Center |
Bogie K.M.,Case Western Reserve University
Journal of Tissue Viability | Year: 2013
Study aim Some individuals with spinal cord injury (SCI) remain pressure ulcer (PU) free whilst others experience a recurring cycle of tissue breakdown. Detailed analysis of gluteal muscle characteristics may provide insights to local tissue viability variability. The study hypothesis was that SCI individuals have altered muscle composition compared to able-bodied (AB). Materials Ten AB and ten SCI received a supine pelvic CT scan, with contrast. Methods Cross-sectional area (CSA) and overall muscle volume were derived using image analysis. Gluteal muscle tissue type was classified at the S2/S3 sacral vertebrae midpoint, the superior greater trochanters margin (GT) and the inferior ischial tuberosities margin (IT) using the linear transformation Hounsfield Unit scale. Results SCI gluteal CSA was less than for AB throughout the muscle, with the greatest relative atrophy at the IT (48%). Average AB gluteal volume was nearly double SCI. Eight SCI had over 20% infiltrative adipose tissue, three with over 50%. SCI gluteal CSA and intramuscular fat infiltration were significantly negatively correlated (p < 0.05). SCI IT axial slices showed less lean muscle and higher intramuscular fat infiltration than more proximally (p < 0.05). Conclusion SCI gluteal muscle characteristics were indicative of impaired tissue viability. SCI disuse muscle atrophy was anticipated; the analytic approach further indicated that intramuscular atrophy was not uniform. SCI muscle composition showed increased proportions of both low density muscle and adipose tissue. CT scan with contrast is effective for gluteal muscle characterization. This assessment technique may contribute to determination of personalized risk for PU development and other secondary complications. © 2013 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.
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.
Fox J.D.,Case Western Reserve University |
Capadona J.R.,Case Western Reserve University |
Capadona J.R.,Advanced Platform Technology Center |
Marasco P.D.,Advanced Platform Technology Center |
Rowan S.J.,Case Western Reserve University
Journal of the American Chemical Society | Year: 2013
Inspired by the water-enhanced mechanical gradient character of the squid beak, we herein report a nanocomposite that mimics both the architecture and properties of this interesting natural material. Similar to the squid beak, we have developed nanocomposites where the degree of cross-linking is controlled along the length of the film. In this study, we utilized tunicate cellulose nanocrystals as the nanofiller that are functionalized with allyl moieties. Using photoinduced thiol-ene chemistry, we have been able to cross-link the CNC nanofiller. In the dry state where strong CNC interactions can occur, only a small mechanical contrast is observed between the cross-linked and uncross-linked samples. However, when the films are exposed to water, which "switches off" the noncovalent CNC interactions, a significant mechanical contrast is observed between the same films. For example, at 20 wt % CNC (in the dry film), an increase in wet modulus from 60 to 300 MPa (∼500% increase) is observed after photoirradiation. Furthermore, we show that the wet modulus can be controlled by altering the UV exposure time which allows access to mechanical gradient films. © 2013 American Chemical Society.
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).
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.
Goldman H.B.,Cleveland Clinic |
Sievert K.-D.,University of Tübingen |
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.