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Parker, Kevin

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Parker

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Parker, Kevin
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Now showing 1 - 10 of 34
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    High-Throughput Coating With Biodegradable Antimicrobial Pullulan Fibres Extends Shelf Life and Reduces Weight Loss in an Avocado Model
    (Springer Science and Business Media LLC, 2022-06-20) Chang, Huibin; Xu, Jie; MacQueen, Luke; Aytac, Zeynep; Peters, Michael; Zimmerman, John; Xu, Tao; Demokritou, Philip; Parker, Kevin
    Food waste and food safety motivate the need for improved food packaging solutions. However, current films/coatings addressing these issues are often limited by inefficient release dynamics that require large quantities of active ingredients. Here, we developed antimicrobial pullulan fiber (APFs) based packaging that are biodegradable and capable of wrapping food substrates, increasing their longevity and food safety. APFs were spun using a high-throughput system termed focused rotary jet spinning (FRJS) with water as the only solvent, allowing the incorporation of nature-derived antimicrobial agents. Using avocados as a representative example, we demonstrate that APF-coated samples had their shelf life extended by inhibited proliferation of natural microflora, as well as reduced weight loss compared to uncoated control samples. This work offers a promising technique to produce scalable, low cost and environmentally friendly biodegradable antimicrobial packaging systems.
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    Metrics for Assessing Cytoskeletal Orientational Correlations and Consistency
    (Public Library of Science, 2015) Drew, Nancy K.; Eagleson, Mackenzie A.; Baldo Jr., Danny B.; Parker, Kevin; Grosberg, Anna
    In biology, organization at multiple scales potentiates biological function. Current advances in staining and imaging of biological tissues provide a wealth of data, but there are few metrics to quantitatively describe these findings. In particular there is a need for a metric that would characterize the correlation and consistency of orientation of different biological constructs within a tissue. We aimed to create such a metric and to demonstrate its use with images of cardiac tissues. The co-orientational order parameter (COOP) was based on the mathematical framework of a classical parameter, the orientational order parameter (OOP). Theorems were proven to illustrate the properties and boundaries of the COOP, which was then applied to both synthetic and experimental data. We showed the COOP to be useful for quantifying the correlation of orientation of constructs such as actin filaments and sarcomeric Z-lines. As expected, cardiac tissues showed perfect correlation between actin filaments and Z-lines. We also demonstrated the use of COOP to quantify the consistency of construct orientation within cells of the same shape. The COOP provides a quantitative tool to characterize tissues beyond co-localization or single construct orientation distribution. In the future, this new parameter could be used to represent the quantitative changes during maturation of cardiac tissue, pathological malformation, and other processes.
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    Traction force microscopy of engineered cardiac tissues
    (Public Library of Science, 2018) Pasqualini, Francesco; Agarwal, Ashutosh; O'Connor, Blakely; Liu, Qihan; Sheehy, Sean P.; Parker, Kevin
    Cardiac tissue development and pathology have been shown to depend sensitively on microenvironmental mechanical factors, such as extracellular matrix stiffness, in both in vivo and in vitro systems. We present a novel quantitative approach to assess cardiac structure and function by extending the classical traction force microscopy technique to tissue-level preparations. Using this system, we investigated the relationship between contractile proficiency and metabolism in neonate rat ventricular myocytes (NRVM) cultured on gels with stiffness mimicking soft immature (1 kPa), normal healthy (13 kPa), and stiff diseased (90 kPa) cardiac microenvironments. We found that tissues engineered on the softest gels generated the least amount of stress and had the smallest work output. Conversely, cardiomyocytes in tissues engineered on healthy- and disease-mimicking gels generated significantly higher stresses, with the maximal contractile work measured in NRVM engineered on gels of normal stiffness. Interestingly, although tissues on soft gels exhibited poor stress generation and work production, their basal metabolic respiration rate was significantly more elevated than in other groups, suggesting a highly ineffective coupling between energy production and contractile work output. Our novel platform can thus be utilized to quantitatively assess the mechanotransduction pathways that initiate tissue-level structural and functional remodeling in response to substrate stiffness.
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    Formation of Multi-Component Extracellular Matrix Protein Fibers
    (Nature Publishing Group UK, 2018) Ahn, Seungkuk; Lee, Keel Yong; Parker, Kevin; Shin, Kwanwoo
    The extracellular matrix (ECM) consists of polymerized protein monomers that form a unique fibrous network providing stability and structural support to surrounding cells. We harnessed the fibrillogenesis mechanisms of naturally occurring ECM proteins to produce artificial fibers with a heterogeneous protein makeup. Using ECM proteins as fibril building blocks, we created uniquely structured multi-component ECM fibers. Sequential incubation of fibronectin (FN) and laminin (LAM) resulted in self-assembly into locally stacked fibers. In contrast, simultaneous incubation of FN with LAM or collagen (COL) produced molecularly stacked multi-component fibers because both proteins share a similar assembly mechanism or possess binding domains specific to each other. Sequential incubation of COL on FN fibers resulted in fibers with sandwiched layers because COL molecules bind to the external surface of FN fibers. By choosing proteins for incubation according to the interplay of their fibrillogenesis mechanisms and their binding domains (exposed when they unfold), we were able to create ECM protein fibers that have never before been observed.
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    Modeling of cardiac muscle thin films: Pre-stretch, passive and active behavior
    (Elsevier, 2012) Shim, Jongmin; Grosberg, Anna; Nawroth, Janna; Parker, Kevin; Bertoldi, Katia
    Recent progress in tissue engineering has made it possible to build contractile bio-hybrid materials that undergo conformational changes by growing a layer of cardiac muscle on elastic polymeric membranes. Further development of such muscular thin films for building actuators and powering devices requires exploring several design parameters, which include the alignment of the cardiac myocytes and the thickness/Young's modulus of elastomeric film. To more efficiently explore these design parameters, we propose a 3-D phenomenological constitutive model, which accounts for both the passive deformation including pre-stretch and the active behavior of the cardiomyocytes. The proposed 3-D constitutive model is implemented within a finite element framework, and can be used to improve the current design of bio-hybrid thin films and help developing bio-hybrid constructs capable of complex conformational changes.
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    Cyclic Strain Induces Dual-Mode Endothelial-Mesenchymal Transformation of the Cardiac Valve
    (Proceedings of the National Academy of Sciences, 2011) Balachandran, Kartik; Alford, Patrick W.; Wylie-Sears, Jill; Goss, Josue; Grosberg, Anna; Bischoff, Joyce; Aikawa, Elena; Levine, Robert; Parker, Kevin
    Endothelial-mesenchymal transformation (EMT) is a critical event for the embryonic morphogenesis of cardiac valves. Inducers of EMT during valvulogenesis include VEGF, TGF-β1, and wnt/β-catenin (where wnt refers to the wingless-type mammary tumor virus integration site family of proteins), that are regulated in a spatiotemporal manner. EMT has also been observed in diseased, strain-overloaded valve leaflets, suggesting a regulatory role for mechanical strain. Although the preponderance of studies have focused on the role of soluble mitogens, we asked if the valve tissue microenvironment contributed to EMT. To recapitulate these microenvironments in a controlled, in vitro environment, we engineered 2D valve endothelium from sheep valve endothelial cells, using microcontact printing to mimic the regions of isotropy and anisotropy of the leaflet, and applied cyclic mechanical strain in an attempt to induce EMT. We measured EMT in response to both low (10%) and high strain (20%), where low-strain EMT occurred via increased TGF-β1 signaling and high strain via increased wnt/β-catenin signaling, suggesting dual strain-dependent routes to distinguish EMT in healthy versus diseased valve tissue. The effect was also directionally dependent, where cyclic strain applied orthogonal to axis of the engineered valve endothelium alignment resulted in severe disruption of cell microarchitecture and greater EMT. Once transformed, these tissues exhibited increased contractility in the presence of endothelin-1 and larger basal mechanical tone in a unique assay developed to measure the contractile tone of the engineered valve tissues. This finding is important, because it implies that the functional properties of the valve are sensitive to EMT. Our results suggest that cyclic mechanical strain regulates EMT in a strain magnitude and directionally dependent manner.
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    Self-Organization of Muscle Cell Structure and Function
    (Public Library of Science (PLoS), 2011) Grosberg, Anna; Kuo, Po-Ling; Guo, Chin-Lin; Geisse, Nicholas A.; Bray, Mark-Anthony; Adams, William J.; Sheehy, Sean Paul; Parker, Kevin
    The organization of muscle is the product of functional adaptation over several length scales spanning from the sarcomere to the muscle bundle. One possible strategy for solving this multiscale coupling problem is to physically constrain the muscle cells in microenvironments that potentiate the organization of their intracellular space. We hypothesized that boundary conditions in the extracellular space potentiate the organization of cytoskeletal scaffolds for directed sarcomeregenesis. We developed a quantitative model of how the cytoskeleton of neonatal rat ventricular myocytes organizes with respect to geometric cues in the extracellular matrix. Numerical results and in vitro assays to control myocyte shape indicated that distinct cytoskeletal architectures arise from two temporally-ordered, organizational processes: the interaction between actin fibers, premyofibrils and focal adhesions, as well as cooperative alignment and parallel bundling of nascent myofibrils. Our results suggest that a hierarchy of mechanisms regulate the self-organization of the contractile cytoskeleton and that a positive feedback loop is responsible for initiating the break in symmetry, potentiated by extracellular boundary conditions, is required to polarize the contractile cytoskeleton.
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    Mechanotransduction: the role of mechanical stress, myocyte shape, and cytoskeletal architecture on cardiac function
    (Springer Nature, 2011) McCain, Megan L.; Parker, Kevin
    Mechanotransduction refers to the conversion of mechanical forces into biochemical or electrical signals that initiate structural and functional remodeling in cells and tissues. The heart is a kinetic organ whose form changes considerably during development and disease, requiring cardiac myocytes to be mechanically durable and capable of fusing a variety of environmental signals on different time scales. During physiological growth, myocytes adaptively remodel to mechanical loads. Pathological stimuli can induce maladaptive remodeling. In both of these conditions, the cytoskeleton plays a pivotal role in both sensing mechanical stress and mediating structural remodeling and functional responses within the myocyte.
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    Nanowired three-dimensional cardiac patches
    (Springer Nature, 2011) Dvir, Tal; Timko, Brian; Brigham, Mark Daniel; Naik, Shreesh R.; Karajanagi, Sandeep; Levy, Oren; Jin, Hongwei; Parker, Kevin; Langer, Robert; Kohane, Daniel
    Engineered cardiac patches for treating damaged heart tissues after a heart attack are normally produced by seeding heart cells within three-dimensional porous biomaterial scaffolds. These biomaterials, which are usually made of either biological polymers such as alginate or synthetic polymers such as poly(lactic acid) (PLA), help cells organize into functioning tissues, but poor conductivity of these materials limits the ability of the patch to contract strongly as a unit. Here, we show that incorporating gold nanowires within alginate scaffolds can bridge the electrically resistant pore walls of alginate and improve electrical communication between adjacent cardiac cells. Tissues grown on these composite matrices were thicker and better aligned than those grown on pristine alginate and when electrically stimulated, the cells in these tissues contracted synchronously. Furthermore, higher levels of the proteins involved in muscle contraction and electrical coupling are detected in the composite matrices. It is expected that the integration of conducting nanowires within three-dimensional scaffolds may improve the therapeutic value of current cardiac patches.