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Search Results for all work with filters:

  • Engineering, Biomedical

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Article

Engineering fibrin polymers through engagement of alternative polymerization mechanisms

by Sarah E. Stabenfeldt; Merek Gourley; Laxminarayanan Krishnan; James B. Hoying; Thomas Barker

2012

Subjects
  • Engineering, Biomedical
  • File Download
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Abstract:Close

Fibrin is an attractive material for regenerative medicine applications. It not only forms a polymer but also contains cryptic matrikines that are released upon its activation/degradation and enhance the regenerative process. Despite this advantageous biology associated with fibrin, commercially available systems (e.g. TISSEEL) display limited regenerative capacity. This limitation is in part due to formulations that are optimized for tissue sealant applications and result in dense fibrous networks that limit cell infiltration. Recent evidence suggests that polymerization knob 'B' engagement of polymerization hole 'b' activates an alternative polymerization mechanism in fibrin, which may result in altered single fiber mechanical properties. We hypothesized that augmenting fibrin polymerization through the addition of PEGylated knob peptides with specificity to hole 'b' (AHRPYAAC-PEG) would result in distinct fibrin polymer architectures with grossly different physical properties. Polymerization dynamics, polymer architecture, diffusivity, viscoelasticity, and degradation dynamics were analyzed. Results indicate that specific engagement of hole 'b' with PEGylated knob 'B' conjugates during polymerization significantly enhances the porosity of and subsequent diffusivity through fibrin polymers. Paradoxically, these polymers also display increased viscoelastic properties and decreased susceptibility to degradation. As a result, fibrin polymer strength was significantly augmented without any adverse effects on angiogenesis within the modified polymers.

Article

Extracellular matrix signaling in morphogenesis and repair

by Kelly C. Clause; Thomas Barker

2013

Subjects
  • Engineering, Biomedical
  • File Download
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Abstract:Close

The extracellular matrix (ECM) is critically important for many cellular processes including growth, differentiation, survival, and morphogenesis. Cells remodel and reshape the ECM by degrading and reassembling it, playing an active role in sculpting their surrounding environment and directing their own phenotypes. Both mechanical and biochemical molecules influence ECM dynamics in multiple ways; by releasing small bioactive signaling molecules, releasing growth factors stored within the ECM, eliciting structural changes to matrix proteins which expose cryptic sites and by degrading matrix proteins directly. The dynamic reciprocal communication between cells and the ECM plays a fundamental roll in tissue development, homeostasis, and wound healing.

Article

Impact of simulated MitraClip on forward flow obstruction in the setting of mitral leaflet tethering: An in vitro investigation

by Charles H. Bloodworth; Eric L. Pierce; Keshav Kohli; Nancy J. Deaton; Kaitlin J. Jones; Radhika Duvvuri; Norihiko Kamioka; Vasilis Babaliaros; Ajit Yoganathan

2018

Subjects
  • Health Sciences, Medicine and Surgery
  • Engineering, Biomedical
  • File Download
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Abstract:Close

Objectives: We aimed to evaluate diastolic leaflet tethering as a factor that may cause mitral stenosis (MS) after simulated MitraClip implantation, using an in vitro left heart simulator. Background: Leaflet tethering commonly seen in functional mitral regurgitation may be a significant factor affecting the severity of MS after MitraClip implantation. Methods: A left heart simulator with excised ovine mitral valves (N = 6), and custom edge-to-edge clip devices (GTclip) was used to mimic implantation of MitraClip in a variety of positions. Anterior mitral leaflet (AML) tethering severity was varied for each case (leaflet excursion of 75°, 60°, and 45°, consistent with mild, moderate and severe tethering), and the baseline mitral annular area (MAA) was varied across samples (3.6–4.8 cm2). The resulting mitral valve area (MVA), and peak/mean mitral valve gradient (MVG) were measured in each case. Results: AML tethering severity was a highly significant factor increasing MVG and decreasing MVA (P < 0.001). When GTclip placement was simulated with severe AML tethering, mean MVG >5 mmHg resulted more frequently than with GTclip placement alone (46% vs. 4%, respectively). However, severe AML tethering alone significantly reduced baseline MVA to 3.6 ± 0.2 cm2, and increased baseline MVG to 3.0 ± 0.4 mmHg. At MAA above 4.7 cm2, severe AML tethering did not cause moderate MS, even with placement of two GTclips (95% confidence). Conclusions: Our results show that diastolic AML tethering may predispose to MS after clip placement, however, MS was not observed when baseline MVA was above 4.0 cm2. Severity of AML tethering may be an important criterion in selecting patients for edge-to-edge repair.

Article

Effects of structural properties of electrospun TiO2 nanofiber meshes on their osteogenic potential

by Xiaokun Wang; Rolando A. Gittens; Rosemary Song; Rina Tannenbaum; Rene Olivares-Navarrete; Zvi Schwartz; Haifeng Chen; Barbara Boyan

2012

Subjects
  • Engineering, Biomedical
  • File Download
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Abstract:Close

Ideal outcomes in the field of tissue engineering and regenerative medicine involve biomaterials that can enhance cell differentiation and production of local factors for natural tissue regeneration without the use of systemic drugs. Biomaterials typically used in tissue engineering applications include polymeric scaffolds that mimic the three-dimensional structural environment of the native tissue, but these are often functionalized with proteins or small peptides to improve their biological performance. For bone applications, titanium implants, or more appropriately the TiO 2 passive oxide layer formed on their surface, have been shown to enhance osteoblast differentiation in vitro and to promote osseointegration in vivo. In this study we evaluated the effect on osteoblast differentiation of pure TiO 2 nanofiber meshes with different surface microroughness and nanofiber diameters, prepared by the electrospinning method. MG63 cells were seeded on TiO 2 meshes, and cell number, differentiation markers and local factor production were analyzed. The results showed that cells grew throughout the entire surfaces and with similar morphology in all groups. Cell number was sensitive to surface microroughness, whereas cell differentiation and local factor production was regulated by both surface roughness and nanofiber diameter. These results indicate that scaffold structural cues alone can be used to drive cell differentiation and create an osteogenic environment without the use of exogenous factors.

Article

Diagnostic biomarkers for renal cell carcinoma: selection using novel bioinformatics systems for microarray data analysis

by Adeboye O. Osunkoya; Qiqin Yin-Goen; John H. Phan; Richard A Moffitt; Todd H Stokes; May D Wang; Andrew N Young

2009

Subjects
  • Health Sciences, Pathology
  • Engineering, Biomedical
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Summary The differential diagnosis of clear cell, papillary and chromophobe renal cell carcinoma is clinically important, because these tumor subtypes are associated with different pathobiology and clinical behavior. For cases in which histopathology is equivocal, immunohistochemistry and quantitative RT-PCR can assist in the differential diagnosis by measuring expression of subtype-specific biomarkers. Several renal tumor biomarkers have been discovered in expression microarray studies. However, due to heterogeneity of gene and protein expression, additional biomarkers are needed for reliable diagnostic classification. We developed novel bioinformatics systems to identify candidate renal tumor biomarkers from the microarray profiles of 45 clear cell, 16 papillary and 10 chromophobe renal cell carcinoma; the microarray data was derived from two independent published studies. The ArrayWiki biocomputing system merged the microarray datasets into a single file, so gene expression could be analyzed from a larger number of tumors. The caCORRECT system removed non-random sources of error from the microarray data, and the omniBioMarker system analyzed data with several gene-ranking algorithms, in order to identify algorithms effective at recognizing previously described renal tumor biomarkers. We predicted these algorithms would also be effective at identifying unknown biomarkers that could be verified by independent methods. We selected six novel candidate biomakers from the omniBioMarker analysis, and verified their differential expression in formalin-fixed paraffin-embedded tissues by quantitative RT-PCR and immunohistochemistry. The candidate biomarkers were carbonic anhydrase IX, ceruloplasmin, schwannomin-interacting protein 1, E74-like factor 3, cytochrome c oxidase subunit 5a and acetyl-CoA acetyltransferase 1. Quantitative RT-PCR was performed on 17 clear cell, 13 papillary and 7 chromophobe renal cell carcinoma. Carbonic anhydrase IX and ceruloplasmin were overexpressed in clear cell renal cell carcinoma; schwannomin-interacting protein 1 and E74-like factor 3 were overexpressed in papillary renal cell carcinoma; and cytochrome c oxidase subunit 5a and acetyl-CoA acetyltransferase 1 were overexpressed in chromophobe renal cell carcinoma. Immunohistochemistry was performed on tissue microarrays containing 66 clear cell, 16 papillary and 12 chromophobe renal cell carcinoma. Cytoplasmic carbonic anhydrase IX staining was significantly associated with clear cell renal cell carcinoma. Strong cytoplasmic schwannomin-interacting protein 1 and cytochrome c oxidase subunit 5a staining were significantly more frequent in papillary and chromophobe renal cell carcinoma, respectively. In summary, we developed a novel process for identifying candidate renal tumor biomarkers from microarray data, and verifying differential expression in independent assays. The tumor biomarkers have potential utility as a multiplex expression panel for classifying renal cell carcinoma with equivocal histology. Biomarker expression assays are increasingly important for renal cell carcinoma diagnosis, as needle core biopsies become more common and different therapies for tumor subtypes continue to be developed.

Article

Identification of side- and shear-dependent microRNAs regulating porcine aortic valve pathogenesis

by Swetha Rathan; Casey J. Ankeny; Sivakkumar Arjunon; Zannatul Ferdous; Sandeep Kumar; Joan Fernandez Esmerats; Jack M. Heath; Robert Nerem; Ajit Yoganathan; Hanjoong Jo

2016

Subjects
  • Engineering, Biomedical
  • Health Sciences, General
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Aortic valve (AV) calcification is an inflammation driven process that occurs preferentially in the fibrosa. To explore the underlying mechanisms, we investigated if key microRNAs (miRNA) in the AV are differentially expressed due to disturbed blood flow (oscillatory shear (OS)) experienced by the fibrosa compared to the ventricularis. To identify the miRNAs involved, endothelial-enriched RNA was isolated from either side of healthy porcine AVs for microarray analysis. Validation using qPCR confirmed significantly higher expression of 7 miRNAs (miR-100, -130a, -181a/b, -199a-3p, -199a-5p, and -214) in the fibrosa versus the ventricularis. Upon bioinformatics analysis, miR-214 was selected for further investigation using porcine AV leaflets in an ex vivo shear system. Fibrosa and ventricularis sides were exposed to either oscillatory or unidirectional pulsatile shear for 2 days and 3 &7 days in regular and osteogenic media, respectively. Higher expression of miR-214, increased thickness of the fibrosa, and calcification was observed when the fibrosa was exposed to OS compared to the ventricularis. Silencing of miR-214 by anti-miR-214 in whole AV leaflets with the fibrosa exposed to OS significantly increased the protein expression of TGFβ1 and moderately increased collagen content but did not affect AV calcification. Thus, miR-214 is identified as a side- and shear-dependent miRNA that regulates key mechanosensitive gene in AV such as TGFβ1.

Article

Stair negotiation made easier using novel interactive energy-recycling assistive stairs.

by Yun Seong Song; Sehoon Ha; Hsiang Hsu; Lena Ting; C. Karen Liu

2017

Subjects
  • Engineering, Mechanical
  • Engineering, Biomedical
  • Health Sciences, Rehabilitation and Therapy
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Here we show that novel, energy-recycling stairs reduce the amount of work required for humans to both ascend and descend stairs. Our low-power, interactive, and modular steps can be placed on existing staircases, storing energy during stair descent and returning that energy to the user during stair ascent. Energy is recycled through event-triggered latching and unlatching of passive springs without the use of powered actuators. When ascending the energy-recycling stairs, naive users generated 17.4 ± 6.9% less positive work with their leading legs compared to conventional stairs, with the knee joint positive work reduced by 37.7 ± 10.5%. Users also generated 21.9 ± 17.8% less negative work with their trailing legs during stair descent, with ankle joint negative work reduced by 26.0 ± 15.9%. Our low-power energy-recycling stairs have the potential to assist people with mobility impairments during stair negotiation on existing staircases.

Article

The Analytic Information Warehouse (AIW): a Platform for Analytics using Electronic Health Record Data

by Andrew Post; Tahsin Kurc; Sharath Cholleti; Jingjing Gao; Xia Lin; William A Bornstein; Dedra Cantrell; David Levine; Sam Hohmann; Joel H Saltz

2013

Subjects
  • Engineering, Biomedical
  • Health Sciences, Pathology
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Objective To create an analytics platform for specifying and detecting clinical phenotypes and other derived variables in electronic health record (EHR) data for quality improvement investigations. Materials and Methods We have developed an architecture for an Analytic Information Warehouse (AIW). It supports transforming data represented in different physical schemas into a common data model, specifying derived variables in terms of the common model to enable their reuse, computing derived variables while enforcing invariants and ensuring correctness and consistency of data transformations, long-term curation of derived data, and export of derived data into standard analysis tools. It includes software that implements these features and a computing environment that enables secure high-performance access to and processing of large datasets extracted from EHRs. Results We have implemented and deployed the architecture in production locally. The software is available as open source. We have used it as part of hospital operations in a project to reduce rates of hospital readmission within 30 days. The project examined the association of over 100 derived variables representing disease and co-morbidity phenotypes with readmissions in five years of data from our institution’s clinical data warehouse and the UHC Clinical Database (CDB). The CDB contains administrative data from over 200 hospitals that are in academic medical centers or affiliated with such centers. Discussion and Conclusion A widely available platform for managing and detecting phenotypes in EHR data could accelerate the use of such data in quality improvement and comparative effectiveness studies.

Article

Strength of resting state functional connectivity and local GABA concentrations predict oral reading of real and pseudo-words

by Lisa C. Krishnamurthy; Venkatagiri Krishnamurthy; Bruce Crosson; Douglas L. Rothman; Dina M. Schwam; Daphne Greenberg; Kenneth R. Pugh; Robin D. Morris

2019

Subjects
  • Biology, Neuroscience
  • Psychology, Cognitive
  • Engineering, Biomedical
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Reading is a learned activity that engages multiple cognitive systems. In a cohort of typical and struggling adult readers we show evidence that successful oral reading of real words is related to gamma-amino-butyric acid (GABA) concentration in the higher-order language system, whereas reading of unfamiliar pseudo-words is not related to GABA in this system. We also demonstrate the capability of resting state functional connectivity (rsFC) combined with GABA measures to predict single real word compared to pseudo-word reading performance. Results show that the strength of rsFC between left fusiform gyrus (L-FG) and higher-order language systems predicts oral reading behavior of real words, irrespective of the local concentration of GABA. On the other hand, pseudo-words, which require grapheme-to-phoneme conversion, are not predicted by the connection between L-FG and higher-order language system. This suggests that L-FG may have a multi-functional role: lexical processing of real words and grapheme-to-phoneme processing of pseudo-words. Additionally, rsFC between L-FG, pre-motor, and putamen areas are positively related to the oral reading of both real and pseudo-words, suggesting that text may be converted into a phoneme sequence for speech initiation and production regardless of whether the stimulus is a real word or pseudo-word. In summary, from a systems neuroscience perspective, we show that: (i) strong rsFC between higher order visual, language, and pre-motor areas can predict and differentiate efficient oral reading of real and pseudo-words. (ii) GABA measures, along with rsFC, help to further differentiate the neural pathways for previously learned real words versus unfamiliar pseudo-words.

Article

Folate Receptor-Targeted Antioxidant Therapy Ameliorates Renal Ischemia-Reperfusion Injury

by Sarah F. Knight; Kousik Kundu; Giji Joseph; Sergey Dikalov; Daiana Weiss; Niren Murthy; W Robert Taylor

2012

Subjects
  • Engineering, Biomedical
  • Biology, Physiology
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Antioxidant therapy can protect against ischemic injury, but the inability to selectively target the kidney would require extremely high doses to achieve effective local concentrations of drug. Here, we developed a directed therapeutic that specifically targets an antioxidant to renal proximal tubule cells via the folate receptor. Because a local increase in superoxide contributes to renal ischemic injury, we created the folate-antioxidant conjugate 4-hydroxy-Tempo (tempol)-folate to target folate receptors, which are highly expressed in the proximal tubule. Dihydroethidium high-performance liquid chromatography demonstrated that conjugated tempol retained its efficacy to scavenge superoxide in proximal tubule cells. In a mouse model of renal ischemia-reperfusion injury, tempol-folate reduced renal superoxide levels more effectively than tempol alone. Furthermore, electron spin resonance revealed the successful targeting of the tempol-folate conjugate to the kidney and other tissues expressing folate receptors. Administration of tempol-folate protected the renal function of mice after ischemia-reperfusion injury and inhibited infiltration of macrophages. In conclusion, kidney-specific targeting of an antioxidant has therapeutic potential to prevent renal ischemic injury. Conjugation of other pharmaceuticals to folate may also facilitate the development of treatments for other kidney diseases.
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