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Articles 1 - 11 of 11
Full-Text Articles in Engineering
Progressive Hypoxia-On-A-Chip: An In Vitro Oxygen Gradient Model For Capturing The Effects Of Hypoxia On Primary Hepatocytes In Health And Disease, Young Bok Abraham Kang, Jinsu Eo, Beyza Bulutoglu, Martin L. Yarmush, O. Berk Usta
Progressive Hypoxia-On-A-Chip: An In Vitro Oxygen Gradient Model For Capturing The Effects Of Hypoxia On Primary Hepatocytes In Health And Disease, Young Bok Abraham Kang, Jinsu Eo, Beyza Bulutoglu, Martin L. Yarmush, O. Berk Usta
Faculty Publications - Biomedical, Mechanical, and Civil Engineering
Oxygen is vital to the function of all tissues including the liver and lack of oxygen, that is, hypoxia can result in both acute and chronic injuries to the liver in vivo and ex vivo. Furthermore, a permanent oxygen gradient is naturally present along the liver sinusoid, which plays a role in the metabolic zonation and the pathophysiology of liver diseases. Accordingly, here, we introduce an in vitro microfluidic platform capable of actively creating a series of oxygen concentrations on a single continuous microtissue, ranging from normoxia to severe hypoxia. This range approximately captures both the physiologically relevant oxygen gradient …
Metabolic Patterning On A Chip: Towards In Vitro Liver Zonation Of Primary Rat And Human Hepatocytes, Young Bok (Abraham) Kang, Jinsu Eo, Safak Mert, Martin L. Yarmush, O. Berk Usta
Metabolic Patterning On A Chip: Towards In Vitro Liver Zonation Of Primary Rat And Human Hepatocytes, Young Bok (Abraham) Kang, Jinsu Eo, Safak Mert, Martin L. Yarmush, O. Berk Usta
Faculty Publications - Biomedical, Mechanical, and Civil Engineering
An important number of healthy and diseased tissues shows spatial variations in their metabolic capacities across the tissue. The liver is a prime example of such heterogeneity where the gradual changes in various metabolic activities across the liver sinusoid is termed as “zonation” of the liver. Here, we introduce the Metabolic Patterning on a Chip (MPOC) platform capable of dynamically creating metabolic patterns across the length of a microchamber of liver tissue via actively enforced gradients of various metabolic modulators such as hormones and inducers. Using this platform, we were able to create continuous liver tissues of both rat and …
Human Liver Sinusoid On A Chip For Hepatitis B Virus Replication Study, Young Bok (Abraham) Kang, Siddhartha Rawat, Nicholas Duchemin, Michael Bouchard, Moses Noh
Human Liver Sinusoid On A Chip For Hepatitis B Virus Replication Study, Young Bok (Abraham) Kang, Siddhartha Rawat, Nicholas Duchemin, Michael Bouchard, Moses Noh
Faculty Publications - Biomedical, Mechanical, and Civil Engineering
We have developed a miniature human liver (liver-sinusoid-on-a-chip) model using a dual microchannel separated by a porous membrane. Primary human hepatocytes and immortalized bovine aortic endothelial cells were co-cultured on opposite sides of a microporous membrane in a dual microchannel with continuous perfusion. Primary human hepatocytes in this system retained their polygonal morphology for up to 26 days, while hepatocytes cultured in the absence of bovine aortic endothelial cells lost their morphology within a week. In order to demonstrate the utility of our human-liver-sinusoid-on-a-chip, human hepatocytes in this system were directly infected by Hepatitis B Virus (HBV). Expression of the …
Liver Sinusoid On A Chip: Long-Term Layered Co-Culture Of Primary Rat Hepatocytes And Endothelial Cells In Microfluidic Platforms, Young Bok (Abraham) Kang, Temitope R. Sodunke, Jason Lamontagne, Joseph Cirillo, Caroline Rajiv, Michael J. Bouchard, Moses Noh
Liver Sinusoid On A Chip: Long-Term Layered Co-Culture Of Primary Rat Hepatocytes And Endothelial Cells In Microfluidic Platforms, Young Bok (Abraham) Kang, Temitope R. Sodunke, Jason Lamontagne, Joseph Cirillo, Caroline Rajiv, Michael J. Bouchard, Moses Noh
Faculty Publications - Biomedical, Mechanical, and Civil Engineering
We describe the generation of microfluidic platforms for the co-culture of primary hepatocytes and endothelial cells; these platforms mimic the architecture of a liver sinusoid. This paper describes a progressional study of creating such a liver sinusoid on a chip system. Primary rat hepatocytes (PRHs) were co-cultured with primary or established endothelial cells in layers in single and dual microchannel configurations with or without continuous perfusion. Cell viability and maintenance of hepatocyte functions were monitored and compared for diverse experimental conditions. When primary rat hepatocytes were co-cultured with immortalized bovine aortic endothelial cells (BAECs) in a dual microchannel with continuous …
The Influence Of Partial And Full Thickness Tears On Infraspinatus Tendon Strain Patterns, Kayt E. Frisch, David Marcu, Geoffrey S. Baer, Darryl G. Thelen, Ray Vanderby
The Influence Of Partial And Full Thickness Tears On Infraspinatus Tendon Strain Patterns, Kayt E. Frisch, David Marcu, Geoffrey S. Baer, Darryl G. Thelen, Ray Vanderby
Faculty Publications - Biomedical, Mechanical, and Civil Engineering
Tears on the bursal and articular sides of the rotator cuff tendons are known to behave differently and strain is thought to play a role in this difference. This study investigates the effect of tear location on the changes in three strain measurements (grip-to-grip, insertion, and mid-substance tissue) in a sheep infraspinatus tendon model during axial loading. We introduced a 14mm wide defect near the insertion from either the articular or bursal side of the tendon to three depths (3 mm, 7mm & full) progressively. For each condition, tendons were sinusoidally stretched (4% at 0.5 Hz) while insertion and midsubstance …
Layered Long Term Co-Culture Of Hepatocytes And Endothelial Cells On A Transwell Membrane: Toward Engineering The Liver Sinusoid, Young Bok (Abraham) Kang, Siddhartha Rawat, Joseph Cirillo, Michael Bouchard, Hongseok (Moses) Noh
Layered Long Term Co-Culture Of Hepatocytes And Endothelial Cells On A Transwell Membrane: Toward Engineering The Liver Sinusoid, Young Bok (Abraham) Kang, Siddhartha Rawat, Joseph Cirillo, Michael Bouchard, Hongseok (Moses) Noh
Faculty Publications - Biomedical, Mechanical, and Civil Engineering
This paper presents a novel liver model that mimics the liver sinusoid where most liver activities occur. A key aspect of our current liver model is a layered co-culture of primary rat hepatocytes (PRHs) and primary rat liver sinusoidal endothelial cells (LSECs) or bovine aortic endothelial cells (BAECs) on a transwell membrane. When a layered co-culture was attempted with a thin matrigel layer placed between hepatocytes and endothelial cells to mimic the Space of Disse, the cells did not form completely separated monolayers. However, when hepatocytes and endothelial cells were cultured on the opposite sides of a transwell membrane, PRHs …
Interleukin Expression After Injury And The Effects Of Interleukin-1 Receptor Antagonist, Connie S. Chamberlain, Ellen M. Leiferman, Kayt E. Frisch, Stacey L. Brickson, William L. Murphy, Geoffrey S. Baer
Interleukin Expression After Injury And The Effects Of Interleukin-1 Receptor Antagonist, Connie S. Chamberlain, Ellen M. Leiferman, Kayt E. Frisch, Stacey L. Brickson, William L. Murphy, Geoffrey S. Baer
Faculty Publications - Biomedical, Mechanical, and Civil Engineering
Ligament and tendon repair involves a complex series of coordinated events orchestrated by various cell types, cytokines and other factors. The repair process extends months to years and results in scar tissue mechanically inferior to native tissue. This is in clear contrast to tissue "regeneration" which would recapitulate the native tissue. Numerous approaches to stimulate a regenerative scenario have been attempted, including tissue-engineering, non-steroidal anti-inflammatories, ultrasonic, or electrical stimulation, but none have resulted in complete regeneration. In pursuit of a more regenerative outcome, it is important to understand the fundamentals of the normal healing process. Previous work from our lab …
Quantification Of Collagen Organization Using Fractal Dimensions And Fourier Transforms, Kayt E. Frisch, Sarah E. Duenwald-Kuehl, Hirohito Kobayashi, Connie S. Chamberlain, Roderic S. Lakes, Ray Vanderby Jr.
Quantification Of Collagen Organization Using Fractal Dimensions And Fourier Transforms, Kayt E. Frisch, Sarah E. Duenwald-Kuehl, Hirohito Kobayashi, Connie S. Chamberlain, Roderic S. Lakes, Ray Vanderby Jr.
Faculty Publications - Biomedical, Mechanical, and Civil Engineering
Collagen fibers and fibrils that comprise tendons and ligaments are disrupted or damaged during injury. Fibrillogenesis during healing produces a matrix that is initially quite disorganized, but remodels over time to resemble, but not replicate, the original roughly parallel microstructure. Quantification of these changes is traditionally a laborious and subjective task. In this work we applied two automated techniques, fast Fourier transformation (FFT) and fractal dimension analysis (FA) to quantify the organization of collagen fibers or fibrils. Using multi-photon images of collagen fibers obtained from rat ligament we showed that for healing ligaments, FA differentiates more clearly between the different …
The Influence Of Macrophage Depletion On Ligament Healing, Connie S. Chamberlain, Ellen M. Leiferman, Kayt E. Frisch, Sijian Wang, Xipei Yang, Nico Van Rooijen, Geoff S. Baer, Stacey L. Brickson, Ray Vanderby
The Influence Of Macrophage Depletion On Ligament Healing, Connie S. Chamberlain, Ellen M. Leiferman, Kayt E. Frisch, Sijian Wang, Xipei Yang, Nico Van Rooijen, Geoff S. Baer, Stacey L. Brickson, Ray Vanderby
Faculty Publications - Biomedical, Mechanical, and Civil Engineering
Despite a complex cascade of cellular events to reconstruct damaged extracellular matrix (ECM), ligament healing results in a mechanically inferior, scar-like tissue. During normal healing, the number of macrophages significantly increases within the wound site. Then, granulation tissue expands into any residual, normal ligamentous tissue (creeping substitution), resulting in a larger region of healing, greater mechanical compromise, and an inefficient repair process. To study the effects of macrophages on the repair process, bilateral, surgical rupture of their medial collateral ligaments (MCLs) was done on rats. Treatment animals received liposome-encapsulated clodronate, 2 days before rupture to ablate phagocytosing macrophages. Ligaments were …
The Influence Of Interleukin-4 On Ligament Healing, Connie S. Chamberlain, Ellen M. Leiferman, Kayt E. Frisch, Sijian Wang, Xipei Yang, Stacey L. Brickson, Ray Vanderby
The Influence Of Interleukin-4 On Ligament Healing, Connie S. Chamberlain, Ellen M. Leiferman, Kayt E. Frisch, Sijian Wang, Xipei Yang, Stacey L. Brickson, Ray Vanderby
Faculty Publications - Biomedical, Mechanical, and Civil Engineering
Despite a complex cascade of cellular events to reconstruct the damaged extracellular matrix, ligament healing results in a mechanically inferior scarred ligament. During normal healing, granulation tissue expands into any residual normal ligamentous tissue (creeping substitution), resulting in a larger region of healing, greater mechanical compromise and an inefficient repair process. To control creeping substitution and possibly enhance the repair process, the antiinflammatory cytokine, interleukin-4 (IL-4), was administered to rats before and after rupture of their medial collateral ligaments. In vitro experiments showed a time-dependent effect on fibroblast proliferation after IL-4 treatment. In vivo treatments with IL-4 (100 ng/mL IV) …
Ultrasound Echo Is Related To Stress And Strain In Tendon, Sarah Duenwald, Hirohito Kobayashi, Kayt E. Frisch, Roderic Lakes, Ray Vanderby Jr.
Ultrasound Echo Is Related To Stress And Strain In Tendon, Sarah Duenwald, Hirohito Kobayashi, Kayt E. Frisch, Roderic Lakes, Ray Vanderby Jr.
Faculty Publications - Biomedical, Mechanical, and Civil Engineering
The mechanical behavior of tendons has been well studied in vitro. A noninvasive method to acquire mechanical data would be highly beneficial. Elastography has been a promising method of gathering in vivo tissue mechanical behavior, but it has inherent limitations. This study presents acoustoelasticity as an alternative ultrasound-based method of measuring tendon stress and strain by reporting a relationship between ultrasonic echo intensity (B-mode ultrasound image brightness) and mechanical behavior of tendon in vitro. Porcine digital flexor tendons were cyclically loaded in a mechanical testing system while an ultrasonic echo response was recorded. We report that echo intensity …