Publications by authors named "Andy T Clark"

4 Publications

  • Page 1 of 1

Dynamic Tuning of Viscoelastic Hydrogels with Carbonyl Iron Microparticles Reveals the Rapid Response of Cells to Three-Dimensional Substrate Mechanics.

ACS Appl Mater Interfaces 2021 May 28;13(18):20947-20959. Epub 2021 Apr 28.

Department of Biomedical Engineering, Rowan University, Glassboro, New Jersey 08028, United States.

Current methods to dynamically tune three-dimensional hydrogel mechanics require specific chemistries and substrates that make modest, slow, and often irreversible changes in their mechanical properties, exclude the use of protein-based scaffolds, or alter the hydrogel microstructure and pore size. Here, we rapidly and reversibly alter the mechanical properties of hydrogels consisting of extracellular matrix proteins and proteoglycans by adding carbonyl iron microparticles (MPs) and applying external magnetic fields. This approach drastically alters hydrogel mechanics: rheology reveals that application of a 4000 Oe magnetic field to a 5 mg/mL collagen hydrogel containing 10 wt % MPs increases the storage modulus from approximately 1.5 to 30 kPa. Cell morphology experiments show that cells embedded within these hydrogels rapidly sense the magnetically induced changes in ECM stiffness. Ca transients are altered within seconds of stiffening or subsequent softening, and slower but still dynamic changes occur in YAP nuclear translocation in response to time-dependent application of a magnetic field. The near instantaneous change in hydrogel mechanics provides new insight into the effect of changing extracellular stiffness on both acute and chronic changes in diverse cell types embedded in protein-based scaffolds. Due to its flexibility, this method is broadly applicable to future studies interrogating cell mechanotransduction in three-dimensional substrates.
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http://dx.doi.org/10.1021/acsami.0c21868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317442PMC
May 2021

Magneto-Driven Gradients of Diamagnetic Objects for Engineering Complex Tissues.

Adv Mater 2020 Dec 19;32(48):e2005030. Epub 2020 Oct 19.

Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Engineering complex tissues represents an extraordinary challenge and, to date, there have been few strategies developed that can easily recapitulate native-like cell and biofactor gradients in 3D materials. This is true despite the fact that mimicry of these gradients may be essential for the functionality of engineered graft tissues. Here, a non-traditional magnetics-based approach is developed to predictably position naturally diamagnetic objects in 3D hydrogels. Rather than magnetizing the objects within the hydrogel, the magnetic susceptibility of the surrounding hydrogel precursor solution is enhanced. In this way, a range of diamagnetic objects (e.g., polystyrene beads, drug delivery microcapsules, and living cells) are patterned in response to a brief exposure to a magnetic field. Upon photo-crosslinking the hydrogel precursor, object positioning is maintained, and the magnetic contrast agent diffuses out of the hydrogel, supporting long-term construct viability. This approach is applied to engineer cartilage constructs with a depth-dependent cellularity mirroring that of native tissue. These are thought to be the first results showing that magnetically unaltered cells can be magneto-patterned in hydrogels and cultured to generate heterogeneous tissues. This work provides a foundation for the formation of opposing magnetic-susceptibility-based gradients within a single continuous material.
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http://dx.doi.org/10.1002/adma.202005030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723011PMC
December 2020

Tunable and Reversible Substrate Stiffness Reveals a Dynamic Mechanosensitivity of Cardiomyocytes.

ACS Appl Mater Interfaces 2019 Jun 30;11(23):20603-20614. Epub 2019 May 30.

Department of Physics , Bryn Mawr College , Bryn Mawr , Pennsylvania 19010 , United States.

New directions in material applications have allowed for the fresh insight into the coordination of biophysical cues and regulators. Although the role of the mechanical microenvironment on cell responses and mechanics is often studied, most analyses only consider static environments and behavior, however, cells and tissues are themselves dynamic materials that adapt in myriad ways to alterations in their environment. Here, we introduce an approach, through the addition of magnetic inclusions into a soft poly(dimethylsiloxane) elastomer, to fabricate a substrate that can be stiffened nearly instantaneously in the presence of cells through the use of a magnetic gradient to investigate short-term cellular responses to dynamic stiffening or softening. This substrate allows us to observe time-dependent changes, such as spreading, stress fiber formation, Yes-associated protein translocation, and sarcomere organization. The identification of temporal dynamic changes on a short time scale suggests that this technology can be more broadly applied to study targeted mechanisms of diverse biologic processes, including cell division, differentiation, tissue repair, pathological adaptations, and cell-death pathways. Our method provides a unique in vitro platform for studying the dynamic cell behavior by better mimicking more complex and realistic microenvironments. This platform will be amenable to future studies aimed at elucidating the mechanisms underlying mechanical sensing and signaling that influence cellular behaviors and interactions.
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http://dx.doi.org/10.1021/acsami.9b02446DOI Listing
June 2019

A CMOS active pixel sensor system for laboratory- based x-ray diffraction studies of biological tissue.

Phys Med Biol 2008 Feb 10;53(3):655-72. Epub 2008 Jan 10.

Department of Medical Physics and Bioengineering, University College London, London, UK.

X-ray diffraction studies give material-specific information about biological tissue. Ideally, a large area, low noise, wide dynamic range digital x-ray detector is required for laboratory-based x-ray diffraction studies. The goal of this work is to introduce a novel imaging technology, the CMOS active pixel sensor (APS) that has the potential to fulfil all these requirements, and demonstrate its feasibility for coherent scatter imaging. A prototype CMOS APS has been included in an x-ray diffraction demonstration system. An industrial x-ray source with appropriate beam filtration is used to perform angle dispersive x-ray diffraction (ADXRD). Optimization of the experimental set-up is detailed including collimator options and detector operating parameters. Scatter signatures are measured for 11 different materials, covering three medical applications: breast cancer diagnosis, kidney stone identification and bone mineral density calculations. Scatter signatures are also recorded for three mixed samples of known composition. Results are verified using two independent models for predicting the APS scatter signature: (1) a linear systems model of the APS and (2) a linear superposition integral combining known monochromatic scatter signatures with the input polychromatic spectrum used in this case. Cross validation of experimental, modelled and literature results proves that APS are able to record biologically relevant scatter signatures. Coherent scatter signatures are sensitive to multiple materials present in a sample and provide a means to quantify composition. In the future, production of a bespoke APS imager for x-ray diffraction studies could enable simultaneous collection of the transmitted beam and scattered radiation in a laboratory-based coherent scatter system, making clinical transfer of the technique attainable.
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http://dx.doi.org/10.1088/0031-9155/53/3/010DOI Listing
February 2008
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