Resume

• 2016

  Universtity of Delaware

  Materials Science & Engineering

  Universtity of Delaware

  Materials Science & Engineering

• 2014

  Delaware Biotechnology Institute

  Newark

  DE

  Delaware Biotechnology Institute

• 2013

  University of Delaware

  Department of Biomedical Engineering

  Newark

  Delaware

  Assistant Professor

  University of Delaware

  Department of Biomedical Engineering

• 2012

  Duke University

  Department of Biomedical Engineering

  Durham

  North Carolina

  Research Scientist

  Duke University

  Department of Biomedical Engineering

• 2008

  Rice University

  Department of Bioengineering (Laboratory for Biofunctional Materials)

  Houston

  Texas

  • Advisor: Dr. Jennifer West\n\nPrimary Projects:\n• Laser scanning lithography for the fabrication of multifaceted nano- and micropatterned surfaces.\n• Cell-derived

  biomimetic patterning to regulate cytoskeletal architecture.\n• Biochemical versus biophysical influences on directional cell migration.\n\nCollaborative Projects:\n• Non-linear confocal microscopy for dual imaging/treatment of nanoshell targeted cancer cells.\n• Patterned surfaces for spatially-controlled gene expression.

  NIH Nanobiology Postdoctoral Training Fellow & HHMI Postdoctoral Training Fellow

  Rice University

  Department of Bioengineering (Laboratory for Biofunctional Materials)

• 2002

  University of Texas at Austin

  Department of Biomedical Engineering (Nanobiotechnology Laboratory)

  Austin

  Texas

  • Advisor: Dr. Wolfgang Frey\n\n• Nanosphere lithography and orthogonal functionalization for nanopatterning fibronectin.\n• Modulation of cell spreading

  proliferation

  and migration using nanopatterned surfaces.

  NSF Graduate Research Fellow

  BME Tom Collins Research Fellow

  & COE Thrust Fellow

  University of Texas at Austin

  Department of Biomedical Engineering (Nanobiotechnology Laboratory)

  Ph.D.

  • Doctor of Philosophy in Biomedical Engineering (GPA 3.83)\n• Doctoral Portfolio in Nanotechnology\n• Dissertation: “Engineering Endothelial Cell Behavior via Cell-Surface Interactions with Chemically-Defined Nanoscale Adhesion Sites”

  Biomedical Engineering

  The University of Texas at Austin

• 2000

  University of North Carolina at Charlotte (BioHeat and Mass Transfer Laboratory)

  Charlotte

  North Carolina

  • Advisors: Dr. Charles Lee and Dr. Robin Coger\n\n• Design and fabrication of a temperature-controlled microshear chamber.\n• Investigation of endothelial cell response to shear stress at hypothermic temperatures.

  James S. Jones Memorial Scholar & Danielson Endowment Scholar

  University of North Carolina at Charlotte (BioHeat and Mass Transfer Laboratory)

• 1998

  B.S.

  • Bachelor of Science in Mechanical Engineering (GPA 3.93)\n• Thesis: “The Effect of Shear Stress on Endothelial Cells at Hypothermic Temperatures”

  Mechanical Engineering

  The University of North Carolina at Charlotte

  Cell Engineering

  Biotransport Phenomena

• 266

  An apparatus

  computer-readable medium

  and computer-implemented method for identifying

  classifying

  and utilizing object information in one or more image includes receiving an image including a plurality of objects

  segmenting the image to identify one or more objects in the plurality of objects

  analyzing the one or more objects to determine one or more morphological metrics associated with each of the one or more objects

  determining the connectivity of the one or more objects to each other based at least in part on a graphical analysis of the one or more objects

  and mapping the connectivity of the one or more objects to the morphological metrics associated with the one or more objects.

  An Automated Method for Measuring

  Classifying and Matching the Dynamics and Information Passing of Single Objects within an Image

  US 14/459

  Jingzhe Hu

  Rebecca Zaunbrecher

  Byron L. Long

  David T. Ryan

  Application No. PCT/US2018/063787

  University of Delaware Research Foundation Strategic Initiative Award Recipient

  University of Delaware Research Foundation

  University of Delaware Research Foundation Award Recipient

  University of Delaware Research Foundation

  2nd Place: Best Overall Postdoctoral Training Fellowship

  Rice Bioscience Research Collaborative

  Exemplary Achievement in Community Service

  Discover Delaware: Roots

  Rifts

  Reconciliation Lecture Series

  Honorable Mention for Best Paper

  Society for Biomaterials

  MD Anderson TRAMCEL Best Postdoctoral Paper

  MD Anderson - Biomedical Engineering Society Cellular & Molecular Bioengineering Special Interest Group

  NSF Graduate Research Fellowship

  National Science Foundation

  HHMI Postdoctoral Training Fellowship

  Howard Hughes Medical Institute

  Emerging Leader in Biological Engineering

  Journal of Biological Engineering

  HHMI Postdoctoral Training Fellowship

  Howard Hughes Medical Institute

  Professional Development Award

  University of Texas Office of Graduate Studies

  W.M. Keck Foundation Science and Engineering Research Grant Recipient

  W.M. Keck Foundation

  2nd Place: Ph.D. Nanotechnology Portfolio Student Presentation Competition

  University of Texas Center for Nano- and Molecular Science

  NIH Nanobiology Postdoctoral Training Fellowship

  National Institutes of Health - Keck Center of the Gulf Coast Consortia

  NSF CAREER Award

  National Science Foundation

  1st Place: Best Postdoctoral Presentation

  Society for Physical Regulation in Biology & Medicine

  BMES CMBE Short Talk Travel Award

  Biomedical Engineering Society Cellular & Molecular Bioengineering Special Interest Group

  Research Summit Award

  NIH Delaware INBRE

  Thrust Fellowship

  University of Texas College of Engineering

  Biomedical Engineering Society Cellular & Molecular Bioengineering Rising Star Junior Faculty Award

  Biomedical Engineering Society

• Biomaterials

  Regenerative Medicine

  Nanotechnology

  Nanoparticles

  Biomedical Engineering

  AFM

  Mechanical Testing

  Scanning Electron Microscopy

  Bioengineering

  ImageJ

  Stem Cells

  Microfabrication

  Microfluidics

  Confocal Microscopy

  Cell Culture

  Fluorescence Microscopy

  Tissue Engineering

  Biosensors

  Microscopy

  Spectroscopy

  Image-guided

  Laser-based Fabrication of Vascular-derived Microfluidic Networks

  David Mayerich

  This detailed protocol outlines the implementation of image-guided

  laser-based hydrogel degradation for the fabrication of vascular-derived microfluidic networks embedded in PEGDA hydrogels. Here

  we describe the creation of virtual masks that allow for image-guided laser control; the photopolymerization of a micromolded PEGDA hydrogel

  suitable for microfluidic network fabrication and pressure head-driven flow; the setup and use of a commercially available laser scanning confocal microscope paired with a femtosecond pulsed Ti:S laser to induce hydrogel degradation; and the imaging of fabricated microfluidic networks using fluorescent species and confocal microscopy. Much of the protocol is focused on the proper setup and implementation of the microscope software and microscope macro

  as these are crucial steps in using a commercial microscope for microfluidic fabrication purposes that contain a number of intricacies. The image-guided component of this technique allows for the implementation of 3D image stacks or user-generated 3D models

  thereby allowing for creative microfluidic design and for the fabrication of complex microfluidic systems of virtually any configuration. With an expected impact in tissue engineering

  the methods outlined in this protocol could aid in the fabrication of advanced biomimetic microtissue constructs for organ- and human-on-a-chip devices. By mimicking the complex architecture

  tortuosity

  size

  and density of in vivo vasculature

  essential biological transport processes can be replicated in these constructs

  leading to more accurate in vitro modeling of drug pharmacokinetics and disease.

  Image-guided

  Laser-based Fabrication of Vascular-derived Microfluidic Networks

  Junghae Suh

  Arum Han

  Spatial organization of gene expression is a crucial element in the development of complex native tissues

  and the capacity to achieve spatially controlled gene expression profiles in a tissue engineering construct is still a considerable challenge. To give tissue engineers the ability to design specific

  spatially organized gene expression profiles in an engineered construct

  we have investigated the use of microcontact printing to pattern recombinant adeno-associated virus (AAV) vectors on a two dimensional surface as a first proof-of-concept study. AAV is a highly safe

  versatile

  stable

  and easy-to-use gene delivery vector

  making it an ideal choice for this application. We tested the suitability of four chemical surfaces (–CH3

  –COOH

  –NH2

  and –OH) to mediate localized substrate-mediated gene delivery. First

  polydimethylsiloxane stamps were used to create microscale patterns of various selfassembled monolayers on gold-coated glass substrates. Next

  AAV particles carrying genes of interest and human fibronectin (HFN) were immobilized on the patterned substrates

  creating a spatially organized arrangement of gene delivery vectors. Immunostaining studies reveal that –CH3 and –NH2 surfaces result in the most successful adsorption of both AAV and HFN. Lastly

  HeLa cells were used to analyze viral transduction and spatial localization of gene expression. We find that –CH3

  –COOH

  and –NH2 surfaces support complete uniform cell coverage with high gene expression. Notably

  we observe a synergistic effect between HFN and AAV for substrate-mediated gene delivery. Our flexible platform should allow for the specific patterning of various gene and shRNA cassettes

  resulting in spatially defined gene expression profiles that may enable the generation of highly functional tissue.

  Microcontact printing for co-patterning cells and viruses for spatially controlled substrate-mediated gene delivery

  Orthogonally functionalized nanopatterend surfaces presenting discrete domains of fibronectin ranging from 92 to 405 nm were implemented to investigate the influence of limiting adhesion site growth on cell migration. We demonstrate that limiting adhesion site growth to small

  immature adhesions using sub-100 nm patterns induced cells to form a significantly increased number of smaller

  more densely packed adhesions that displayed few interactions with actin stress fibers. Human umbilical vein endothelial cells exhibiting these traits displayed highly dynamic fluctuations in spreading and a 4.8-fold increase in speed compared to cells on non-patterned controls. As adhesions were allowed to mature in size in cells cultured on larger nanopatterns

  222 to 405 nm

  the dynamic fluctuations in spread area and migration began to slow

  yet cells still displayed a 2.1-fold increase in speed compared to controls. As all restrictions on adhesion site growth were lifted using non-patterned controls; cells formed significantly fewer

  less densely packed

  larger

  mature adhesions that acted as terminating sites for actin stress fibers and significantly slower migration. The results revealed an exponential decay in cell speed with increased adhesion site size indicating that preventing the formation of large mature adhesions may disrupt cell stability thereby inducing highly migratory behavior.

  Modulation of Endothelial Cell Migration via Manipulation of Adhesion Site Growth Using Nanopatterned Surfaces

  This protocol describes the implementation of laser scanning lithography (LSL) for the fabrication of multifaceted

  patterned surfaces and for image-guided patterning. This photothermal-based patterning technique allows for selective removal of desired regions of an alkanethiol self-assembled monolayer on a metal film through raster scanning a focused 532 nm laser using a commercially available laser scanning confocal microscope. Unlike traditional photolithography methods

  this technique does not require the use of a physical master and instead utilizes digital “virtual masks” that can be modified “on the fly” allowing for quick pattern modifications. The process to create multifaceted

  micropatterned surfaces

  surfaces that display pattern arrays of multiple biomolecules with each molecule confined to its own array

  is described in detail. The generation of pattern configurations from user-chosen images

  image-guided LSL is also described. This protocol outlines LSL in four basic sections. The first section details substrate preparation and includes cleaning of glass coverslips

  metal deposition

  and alkanethiol functionalization. The second section describes two ways to define pattern configurations

  the first through manual input of pattern coordinates and dimensions using Zeiss AIM software and the second via image-guided pattern generation using a custom-written MATLAB script. The third section describes the details of the patterning procedure and postpatterning functionalization with an alkanethiol

  protein

  and both

  and the fourth section covers cell seeding and culture. We end with a general discussion concerning the pitfalls of LSL and present potential improvements that can be made to the technique.

  Fabrication of Multifaceted

  Micropatterned Surfaces and Image-Guided Patterning Using Laser Scanning Lithography

  David Mayerich

  Paul Ruchhoeft

  Pavel Govyadinov

  Jiaming Guo

  In vivo

  microvasculature provides oxygen

  nutrients

  and soluble factors necessary for cell survival and function. The highly tortuous

  densely-packed

  and interconnected three-dimensional (3D) architecture of microvasculature ensures that cells receive these crucial components. The ability to duplicate microvascular architecture in tissue-engineered models could provide a means to generate large-volume constructs as well as advanced microphysiological systems. Similarly

  the ability to induce realistic flow in engineered microvasculature is crucial to recapitulating in vivo-like flow and transport. Advanced biofabrication techniques are capable of generating 3D

  biomimetic microfluidic networks in hydrogels

  however

  these models can exhibit systemic aberrations in flow due to incorrect boundary conditions. To overcome this problem

  we developed an automated method for generating synthetic augmented channels that induce the desired flow properties within three-dimensional microfluidic networks. These augmented inlets and outlets enforce the appropriate boundary conditions for achieving specified flow properties and create a three-dimensional output useful for image-guided fabrication techniques to create biomimetic microvascular networks.

  Accurate Flow in Augmented Networks (AFAN): An Approach to Generating Three-Dimensional Biomimetic Microfluidic Networks with Controlled Flow

  Mary Dickinson

  An image-guided micropatterning method is demonstrated for generating biomimetic hydrogel scaffolds with two-photon laser scanning photolithography. This process utilizes computational methods to directly translate three-dimensional cytoarchitectural features from labeled tissues into material structures. We use this method to pattern hydrogels that guide cellular organization by structurally and biochemically recapitulating complex vascular niche microenvironments with high pattern fidelity at the microscale.

  Three-Dimensional Biomimetic Patterning in Hydrogels to Guide Cellular Organization

  Cindy Farino

  Metastatic recurrence is a major hurdle to overcome for successful control of cancer-associated death. Residual tumor cells in the primary site

  or disseminated tumor cells in secondary sites

  can lie in a dormant state for long time periods

  years to decades

  before being reactivated into a proliferative growth state. The microenvironmental signals and biological mechanisms that mediate the fate of disseminated cancer cells with respect to cell death

  single cell dormancy

  tumor mass dormancy and metastatic growth

  as well as the factors that induce reactivation

  are discussed in this review. Emphasis is placed on engineered

  in vitro

  biomaterial-based approaches to model tumor dormancy and subsequent reactivation

  with a focus on the roles of extracellular matrix

  secondary cell types

  biochemical signaling and drug treatment. A brief perspective of molecular targets and treatment approaches for dormant tumors is also presented. Advances in tissue-engineered platforms to induce

  model

  and monitor tumor dormancy and reactivation may provide much needed insight into the regulation of these processes and serve as drug discovery and testing platforms.

  Engineered In Vitro Models of Tumor Dormancy and Reactivation

  M.K. Markey

  W. Frey

  A.C. Bovik

  E.M. Blinka

  S.S. Channappayya

  G.S. Muralidhar

  Automated analysis of fluorescence microscopy images of endothelial cells labeled for actin is important for quantifying changes in the actin cytoskeleton. The current manual approach is laborious and inefficient. The goal of our work is to develop automated image analysis methods

  thereby increasing cell analysis throughput. In this study

  we present preliminary results on comparing different algorithms for cell segmentation and image denoising.

  Comparison of Pre-Processing Techniques for Fluorescence Microscopy Images of Cells Labeled for Actin

  This chapter focuses on the implementation of biomimetic surfaces that recapitulate and control one or more aspects of the cellular microenvironment to induce a desired cell response. More specifically

  biomimetic surfaces that mimic in vivo extracellular matrix composition

  density

  gradients

  stiffness

  or topography; those that allow for control over cell shape

  spreading

  or cytoskeletal tension; and those that mimic cell surfaces are discussed.

  Biomimetic Surfaces for Cell Engineering

  Wolfgang Frey

  Investigating stages of maturation of cellular adhesions to the extracellular matrix from the initial binding events to the formation of small focal complexes has been challenging because of the difficulty in fabricating the necessary nanopatterned substrates with controlled biochemical functionality. We present the fabrication and characterization of surfaces presenting fibronectin nanopatterns of controlled size and pitch that provide well-defined cellular adhesion sites against a nonadhesive polyethylene glycol background. The nanopatterned surfaces allow us to control the number of fibronectin proteins within each adhesion site from 9 to 250

  thereby limiting the number of integrins involved in each cell–substrate adhesion. We demonstrate the presence of fibronectin on the nanoislands

  while no protein was observed on the passivated background. We show that the cell adheres to the nanopatterns with adhesions that are much smaller and more evenly distributed than on a glass control. The nanopattern influences cellular proliferation only at longer times

  but influences spreading at both early and later times

  indicating adhesion size and adhesion density play a role in controlling cell adhesion and signaling. However

  the overall density of fibronectin on all patterns is far lower than on homogeneously coated control surfaces

  showing that the local density of adhesion ligands

  not the average density

  is the important parameter for cell proliferation and spreading.

  Nanopatterning of Fibronectin and the Influence of Integrin Clustering on Endothelial Cell Spreading and Proliferation

  Steven M. Kornblau

  Estimating the optimal number of clusters is a major challenge in applying cluster analysis to any type of dataset

  especially to biomedical datasets

  which are high-dimensional and complex. Here

  we introduce an improved method

  Progeny Clustering

  which is stability-based and exceptionally efficient in computing

  to find the ideal number of clusters. The algorithm employs a novel Progeny Sampling method to reconstruct cluster identity

  a co-occurrence probability matrix to assess the clustering stability

  and a set of reference datasets to overcome inherent biases in the algorithm and data space. Our method was shown successful and robust when applied to two synthetic datasets (datasets of two-dimensions and ten-dimensions containing eight dimensions of pure noise)

  two standard biological datasets (the Iris dataset and Rat CNS dataset) and two biological datasets (a cell phenotype dataset and an acute myeloid leukemia (AML) reverse phase protein array (RPPA) dataset). Progeny Clustering outperformed some popular clustering evaluation methods in the ten-dimensional synthetic dataset as well as in the cell phenotype dataset

  and it was the only method that successfully discovered clinically meaningful patient groupings in the AML RPPA dataset.

  Progeny Clustering: a Method to Identify Biological Phenotypes

  The implementation of engineered surfaces presenting micrometer-sized patterns of cell adhesive ligands against a biologically inert background has led to numerous discoveries in fundamental cell biology. While existing surface patterning strategies allow for pattering of a single ligand it is still challenging to fabricate surfaces displaying multiple patterned ligands. To address this issue we implemented Laser Scanning Lithography (LSL)

  a laser-based thermal desorption technique

  to fabricate multifaceted

  micropatterned surfaces that display independent arrays of subcellular-sized patterns of multiple adhesive ligands with each ligand confined to its own array. We demonstrate that LSL is a highly versatile “maskless” surface patterning strategy that provides the ability to create patterns with features ranging from 460 nm to 100 µm

  topography ranging from -1 to 17 nm

  and to fabricate both stepwise and smooth ligand surface density gradients. As validation for their use in cell studies

  surfaces presenting orthogonally interwoven arrays of 1x8 µm elliptical patterns of Gly-Arg-Gly-Asp-terminated alkanethiol self-assembled monolayers and human plasma fibronectin are produced. Human umbilical vein endothelial cells cultured on these multifaceted surfaces form adhesion sites to both ligands simultaneously and utilize both ligands for lamella formation during migration. The ability to create multifaceted

  patterned surfaces with tight control over pattern size

  spacing

  and topography provides a platform to simultaneously investigate the complex interactions of extracellular matrix geometry

  biochemistry

  and topography on cell adhesion and downstream cell behavior.

  Fabrication of Multifaceted Micropatterned Surfaces with Laser Scanning Lithography

  Kelvin H. Lee

  We developed a new approach to fabricate 3D

  hydrogel embedded

  biomimetic microfluidic networks by combining laser-based degradation with image-guided laser control and demonstrated that it can be used to: locally control the concentration and porosity of hydrogels in the desired 3D geometries; fabricate truly 3D

  biomimetic

  capillary-like microfluidic networks; and generate two independent

  yet interacting

  microfluidic networks in close proximity. Using these unique hydrogel modification properties

  we demonstrated: size-based separation of varying molecular weight biomolecules in a single microchannel; vascular-derived microfluidic networks that recapitulate the dense

  tortuous architecture of in vivo vasculature; and interstitial transport between intertwining

  yet independent

  microfluidic systems.

  Fabrication of 3D Biomimetic Microfluidic Networks in Hydrogels

  Mary E. Dickinson

  Taylor F. Birk

  Jingzhe Hu

  Byron L. Long

  Heterogeneity of cell populations can confound population-averaged measurements and obscure important findings or foster inaccurate conclusions. The ability to generate a homogeneous cell population

  at least with respect to a chosen trait

  could significantly aid basic biological research and development of high-throughput assays. Accordingly

  we developed a high-resolution

  image-based patterning strategy to produce arrays of single-cell patterns derived from the morphology or adhesion site arrangement of user-chosen cells of interest (COIs). Cells cultured on both cell-derived patterns displayed a cellular architecture defined by their morphology

  adhesive state

  cytoskeletal organization

  and nuclear properties that quantitatively recapitulated the COIs that defined the patterns. Furthermore

  slight modifications to pattern design allowed for suppression of specific actin stress fibers and direct modulation of adhesion site dynamics. This approach to patterning provides a strategy to produce a more homogeneous cell population

  decouple the influences of cytoskeletal structure

  adhesion dynamics

  and intracellular tension on mechanotransduction-mediated processes

  and a platform for high-throughput cellular assays.

  Recapitulation and Modulation of the Cellular Architecture of a User-Chosen Cell of Interest Using Cell-Derived

  Biomimetic Patterning

  Cell experiments investigating cell behavior as a function of material stiffness are often carried out on the surface of hydrogels. An assumption that the bulk hydrogel mechanical properties represent the surface properties is often employed but in many cases is not valid. In photo-initiated radical polymerization

  photons are absorbed by initiator chromophores generating high energy electrons. As photons progress through the prepolymer solution

  the intensity of light that reaches the distal end of the solution is decreased through this attenuation. This work aims to determine whether light attenuation plays a significant role in local stiffness within a poly(ethylene glycol) diacrylate (PEGDA) hydrogel

  compared to its bulk stiffness.\n\nDifferences in bulk properties were tested by varying the polymerization parameters of hydrogel cylindrical plugs

  including sample thickness (0.7mm – 1.2mm)

  photoinitiator type (EosinY vs LAP)

  PEGDA weight percent

  and exposure time. Mechanical loading data of the plugs was analyzed to reveal the relationships between the physical properties (e.g. thickness

  surface area

  volume) and chemical properties (e.g. monomer and initiator concentrations

  exposure settings). Preliminary data suggests that an appreciable difference in physical properties exists between gels of differing thickness (1.0mm vs 0.3mm based on gel point). The goals of this work are to quantify the extent of this difference based on sample thickness

  and to compare the bulk stiffness data with local surface stiffness measurements obtained using an AFM nano-indentation technique and determine whether changes in bulk properties carry over to changes in surface properties.

  Effects of Light Attenuation on Local and Bulk Mechanical Properties of Photopolymerized PEG Hydrogels

  Mary Dickinson

  Both chemical and mechanical stimuli can dramatically influence cell behavior. By optimizing the signals cells experience

  it may be possible to control the behavior of therapeutic cell populations. In this work

  biomimetic geometries of adhesive ligands

  which recapitulate the morphology of mature cells

  are used to direct human mesenchymal stem cell (HMSC) differentiation toward a desired lineage. Specifically

  adipocytes cultured in 2D are imaged and used to develop biomimetic virtual masks used in laser scanning lithography to form patterned fibronectin surfaces. The impact of adipocyte-derived pattern geometry on HMSC differentiation is compared to the behavior of HMSCs cultured on square and circle geometries

  as well as adipocytederived patterns modified to include high stress regions. HMSCs on adipocyte mimetic geometries demonstrate greater adipogenesis than HMSCs on the other patterns. Greater than 45% of all HMSCs cultured on adipocyte mimetic patterns underwent adipogenesis as compared to approximately 19% of cells on modified adipocyte patterns with higher stress regions. These results are attributed to variations in cytoskeletal tension experienced by cells on the different protein micropatterns. The effects of geometry on adipogenesis are mitigated by the incorporation of a cytoskeletal protein inhibitor; exposure to this inhibitor leads to increased adipogenesis on all patterns examined.

  Biomimetic Surface Patterning Promotes Mesenchymal Stem Cell Differentiation

  The cell and tissue engineering fields have profited immensely through the implementation of highly structured biomaterials. The development and implementation of advanced biofabrication techniques have established new avenues for generating biomimetic scaffolds for a multitude of cell and tissue\nengineering applications. Among these

  laser-based degradation of biomaterials is implemented to achieve user-directed features and functionalities within biomimetic scaffolds. This review offers an overview of the physical mechanisms that govern laser–material interactions and specifically

  laser–\nhydrogel interactions. The influences of both laser and material properties on efficient

  high-resolution hydrogel degradation are discussed and the current application space in cell and tissue engineering is reviewed. This review aims to acquaint readers with the capability and uses of laser-based degradation of biomaterials

  so that it may be easily and widely adopted.

  Fundamentals of Laser-Based Hydrogel Degradation and Applications in Cell and Tissue Engineering

  Rebekah A Drezek

  Nicholas S Riggall

  The goal of this study was to develop near-infrared (NIR) resonant gold-gold sulfide nanoparticles (GGS-NPs) as dual contrast and therapeutic agents for cancer management via multiphoton microscopy followed by higher intensity photoablation. We demonstrate that GGS-NPs exposed to a pulsed

  NIR laser exhibit two-photon induced photoluminescence that can be utilized to visualize cancerous cells in vitro. When conjugated with anti-HER2 antibodies

  these nanoparticles specifically bind SK-BR-3 breast carcinoma cells that over-express the HER2 receptor

  enabling the cells to be imaged via multiphoton microscopy with an incident laser power of 1 mW. Higher excitation power (50 mW) could be employed to induce thermal damage to the cancerous cells

  producing extensive membrane blebbing within seconds leading to cell death. GGS-NPs are ideal multifunctional agents for cancer management because they offer the ability to pinpoint precise treatment sites and perform subsequent thermal ablation in a single setting.

  Antibody-conjugated gold-gold sulfide nanoparticles as multifunctional agents for imaging and therapy of breast cancer

  Robin Coger

  Shailendra Jain

  Hypothermic machine perfusion preservation (MPP) has proven to be a successful technique for hypothermic kidney storage

  however this technology has not successfully been applied to the liver. Recent research has indicated that the endothelial cells lining the liver sinusoids display rounding phenomena during MPP that is not fully understood. In order to gain a better understanding of endothelial cell shear stress response and the factors that induce rounding

  a\ntemperature-controlled micro-shear chamber has been designed and fabricated. The micro-shear chamber has been used to apply shear stresses

  corresponding to those imposed during MPP

  to rat liver primary endothelial cell cultures in order to form an understanding of how these stresses affect endothelial cell morphology. The chamber allows for the application of shear stresses ranging from 0.2 ± .01 dynes/cm2 to 2.3 ± 0.3 dynes/cm2

  corresponding to what occurs during MPP.] Twenty-four hour in vitro experiments with shear stresses ranging from 0 to 1.49 dynes/cm2 at 4 ° C were conducted in order to replicate in vivo conditions of the liver during hypothermic MPP. It has been demonstrated that endothelial cell rounding increases with increasing shear and can be prevented by utilizing low flow rates.

  The Effects of Shear Stress on Endothelial Cells at Hypothermic Temperatures

  Slater