Publications by authors named "Shoshana L Das"

5 Publications

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Extracellular Matrix Alignment Directs Provisional Matrix Assembly and Three Dimensional Fibrous Tissue Closure.

Tissue Eng Part A 2021 Dec 12;27(23-24):1447-1457. Epub 2021 May 12.

Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.

Gap closure is a dynamic process in wound healing, in which a wound contracts and a provisional matrix is laid down, to restore structural integrity to injured tissues. The efficiency of wound closure has been found to depend on the shape of a wound, and this shape dependence has been echoed in various studies. While wound shape itself appears to contribute to this effect, it remains unclear whether the alignment of the surrounding extracellular matrix (ECM) may also contribute. In this study, we investigate the role both wound curvature and ECM alignment have on gap closure in a 3D culture model of fibrous tissue. Using microfabricated flexible micropillars positioned in rectangular and octagonal arrangements, seeded 3T3 fibroblasts embedded in a collagen matrix formed microtissues with different ECM alignments. Wounding these microtissues with a microsurgical knife resulted in wounds with different shapes and curvatures that closed at different rates. Observing different regions around the wounds, we noted local wound curvature did not impact the rate of production of provisional fibronectin matrix assembled by the fibroblasts. Instead, the rate of provisional matrix assembly was lowest emerging from regions of high fibronectin alignment and highest in the areas of low matrix alignment. Our data suggest that the underlying ECM structure affects the shape of the wound as well as the ability of fibroblasts to build provisional matrix, an important step in the process of tissue closure and restoration of tissue architecture. The study highlights an important interplay between ECM alignment, wound shape, and tissue healing that has not been previously recognized and may inform approaches to engineer tissues. Impact statement Current models of tissue growth have identified a role for curvature in driving provisional matrix assembly. However, most tissue repair occurs in fibrous tissues with different levels of extracellular matrix (ECM) alignment. Here, we show how this underlying ECM alignment may affect the ability of fibroblasts to build new provisional matrix, with implications for wound healing and providing insight for engineering of new tissues.
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http://dx.doi.org/10.1089/ten.tea.2020.0332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742281PMC
December 2021

Fast, multiplane line-scan confocal microscopy using axially distributed slits.

Biomed Opt Express 2021 Mar 9;12(3):1339-1350. Epub 2021 Feb 9.

Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston, MA 02215, USA.

The inherent constraints on resolution, speed and field of view have hindered the development of high-speed, three-dimensional microscopy techniques over large scales. Here, we present a multiplane line-scan imaging strategy, which uses a series of axially distributed reflecting slits to probe different depths within a sample volume. Our technique enables the simultaneous imaging of an optically sectioned image stack with a single camera at frame rates of hundreds of hertz, without the need for axial scanning. We demonstrate the applicability of our system to monitor fast dynamics in biological samples by performing calcium imaging of neuronal activity in mouse brains and voltage imaging of cardiomyocytes in cardiac samples.
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http://dx.doi.org/10.1364/BOE.417286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984773PMC
March 2021

Voltage Imaging of Cardiac Cells and Tissue Using the Genetically Encoded Voltage Sensor Archon1.

iScience 2020 Apr 11;23(4):100974. Epub 2020 Mar 11.

Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA. Electronic address:

Precise measurement of action potentials (APs) is needed to observe electrical activity and cellular communication within cardiac tissue. Voltage-sensitive dyes (VSDs) are traditionally used to measure cardiac APs; however, they require acute chemical addition that prevents chronic imaging. Genetically encoded voltage indicators (GEVIs) enable long-term studies of APs without the need of chemical additions, but current GEVIs used in cardiac tissue exhibit poor kinetics and/or low signal to noise (SNR). Here, we demonstrate the use of Archon1, a recently developed GEVI, in hiPSC-derived cardiomyocytes (CMs). When expressed in CMs, Archon1 demonstrated fast kinetics comparable with patch-clamp electrophysiology and high SNR significantly greater than the VSD Di-8-ANEPPS. Additionally, Archon1 enabled monitoring of APs across multiple cells simultaneously in 3D cardiac tissues. These results highlight Archon1's capability to investigate the electrical activity of CMs in a variety of applications and its potential to probe functionally complex in vitro models, as well as in vivo systems.
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http://dx.doi.org/10.1016/j.isci.2020.100974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160579PMC
April 2020

Central nervous system effects of whole-body proton irradiation.

Radiat Res 2014 Jul 17;182(1):18-34. Epub 2014 Jun 17.

a  Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.

Space missions beyond the protection of Earth's magnetosphere expose astronauts to an environment that contains ionizing proton radiation. The hazards that proton radiation pose to normal tissues, such as the central nervous system (CNS), are not fully understood, although it has been shown that proton radiation affects the neurogenic environment, killing neural precursors and altering behavior. To determine the time and dose-response characteristics of the CNS to whole-body proton irradiation, C57BL/6J mice were exposed to 1 GeV/n proton radiation at doses of 0-200 cGy and behavioral, physiological and immunohistochemical end points were analyzed over a range of time points (48 h-12 months) postirradiation. These experiments revealed that proton radiation exposure leads to: 1. an acute decrease in cell division within the dentate gyrus of the hippocampus, with significant differences detected at doses as low as 10 cGy; 2. a persistent effect on proliferation in the subgranular zone, at 1 month postirradiation; 3. a decrease in neurogenesis at doses as low as 50 cGy, at 3 months postirradiation; and 4. a decrease in hippocampal ICAM-1 immunoreactivity at doses as low as 10 cGy, at 1 month postirradiation. The data presented contribute to our understanding of biological responses to whole-body proton radiation and may help reduce uncertainty in the assessment of health risks to astronauts. These findings may also be relevant to clinical proton beam therapy.
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http://dx.doi.org/10.1667/RR13699.1DOI Listing
July 2014
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