ORCID Profile
0000-0002-8963-9796
Current Organisation
Natural Resources Canada
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Biomaterials | Synthesis of Materials | Biomedical Engineering | Nanochemistry and Supramolecular Chemistry | Biochemistry and cell biology | Organic Chemistry | Catalysis and Mechanisms of Reactions | Macromolecular and Materials Chemistry | Physical Organic Chemistry | Polymers and plastics | Cellular Interactions (incl. Adhesion, Matrix, Cell Wall) | Biomaterials | Nanomanufacturing | Nanomaterials | Biomedical engineering | Nanotechnology | Polymers and Plastics | Microtechnology | Protein trafficking | Cellular interactions (incl. adhesion matrix cell wall) | Nanobiotechnology | Mechanobiology | Nanobiotechnology
ANZSRC Socio-Economic Objective (SEO)
Expanding Knowledge in the Chemical Sciences | Human Diagnostics | Expanding Knowledge in the Medical and Health Sciences | Expanding Knowledge in Technology | Diagnostic Methods | Expanding Knowledge in the Physical Sciences | Scientific Instruments | Expanding Knowledge in Engineering | Expanding Knowledge in the Biological Sciences |
Related Links
Publications
C ell shape and the presentation of adhesion ligands guide smooth muscle myogenesis
Publisher: Wiley
Date: 11-02-2016
DOI: 10.1002/JBM.A.35661
Abstract: The reliable generation of smooth muscle cells is important for a number of tissue engineering applications. Human mesenchymal stem cells (MSCs) are a promising progenitor of smooth muscle, with high expression of smooth muscle markers observed in a fraction of isolated cells, which can be increased by introduction of soluble supplements that direct differentiation. Here we demonstrate a new micropatterning technique, where peptides of different ligand affinity can be microcontact printed onto an inert background, to explore MSC differentiation to smooth muscle through controlled biochemical and biophysical cues alone. Using copper-catalyzed alkyne-azide cycloaddition (CuAAC), we patterned our surfaces with RGD peptide ligands-both a linear peptide with low integrin affinity and a cyclic version with high integrin affinity-for the culture of MSCs in shapes with various aspect ratios. At low aspect ratio, ligand affinity is a prime determinant for smooth muscle differentiation, while at high aspect ratio, ligand affinity has less of an effect. Pathway analysis reveals a role for focal adhesion turnover, Rac1, RhoA/ROCK, and calpain during smooth muscle differentiation of MSCs in response to cell shape and the affinity of the cell adhesion interface. Controlling integrin-ligand affinity at the biomaterials interface is important for mediating adhesion but may also prove useful for directing smooth muscle myogenesis. Peptide patterning enables the systematic investigation of single to multiple peptides derived from any protein, at different densities across a biomaterials surface, which has the potential to direct multiple MSC differentiation outcomes without the need for soluble supplements.
Gradient and Dynamic Hydrogel Materials to Probe Dynamics in Cancer Stem Cell Phenotypes
Publisher: American Chemical Society (ACS)
Date: 16-12-2020
Biomaterials directed activation of a cryostable therapeutic secretome in induced pluripotent stem cell derived mesenchymal stromal cells
Publisher: Hindawi Limited
Date: 26-08-2022
DOI: 10.1002/TERM.3347
Abstract: Mesenchymal stem cell therapy has suffered from wide variability in clinical efficacy, largely due to heterogeneous starting cell populations and large-scale cell death during and after implantation. Optimizing the manufacturing process has led to reproducible cell populations that can be cryopreserved for clinical applications. Nevertheless, ensuring a reproducible cell state that persists after cryopreservation remains a significant challenge, and is necessary to ensure reproducible clinical outcomes. Here we demonstrate how matrix-conjugated hydrogel cell culture materials can normalize a population of induced pluripotent stem cell derived mesenchymal stem cells (iPSC-MSCs) to display a defined secretory profile that promotes enhanced neovascularization in vitro and in vivo. Using a protein-conjugated biomaterials screen we identified two conditions-1 kPa collagen and 10 kPa fibronectin coated polyacrylamide gels-that promote reproducible secretion of pro-angiogenic and immunomodulatory cytokines from iPSC-MSCs that enhance tubulogenesis of endothelial cells in Geltrex and neovascularization in chick chorioallantoic membranes. Using defined culture substrates alone, we demonstrate maintenance of secretory activity after cryopreservation for the first time. This advance provides a simple and scalable approach for cell engineering and subsequent manufacturing, toward normalizing and priming a desired cell activity for clinical regenerative medicine.
Mesoporous silicon photonic crystal microparticles: Towards single-cell optical biosensors
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C005340F
Biomechanical, biophysical and biochemical modulators of cytoskeletal remodelling and emergent stem cell lineage commitment
Publisher: Springer Science and Business Media LLC
Date: 19-01-2023
DOI: 10.1038/S42003-022-04320-W
Abstract: Across complex, multi-time and -length scale biological systems, redundancy confers robustness and resilience, enabling adaptation and increasing survival under dynamic environmental conditions this review addresses ubiquitous effects of cytoskeletal remodelling, triggered by biomechanical, biophysical and biochemical cues, on stem cell mechanoadaptation and emergent lineage commitment. The cytoskeleton provides an adaptive structural scaffold to the cell, regulating the emergence of stem cell structure-function relationships during tissue neogenesis, both in prenatal development as well as postnatal healing. Identification and mapping of the mechanical cues conducive to cytoskeletal remodelling and cell adaptation may help to establish environmental contexts that can be used prospectively as translational design specifications to target tissue neogenesis for regenerative medicine. In this review, we summarize findings on cytoskeletal remodelling in the context of tissue neogenesis during early development and postnatal healing, and its relevance in guiding lineage commitment for targeted tissue regeneration. We highlight how cytoskeleton-targeting chemical agents modulate stem cell differentiation and govern responses to mechanical cues in stem cells’ emerging form and function. We further review methods for spatiotemporal visualization and measurement of cytoskeletal remodelling, as well as its effects on the mechanical properties of cells, as a function of adaptation. Research in these areas may facilitate translation of stem cells’ own healing potential and improve the design of materials, therapies, and devices for regenerative medicine.
Induction of muscle-regenerative multipotent stem cells from human adipocytes by PDGF-AB and 5-azacytidine
Publisher: American Association for the Advancement of Science (AAAS)
Date: 15-01-2021
Abstract: Human adipocytes are a source of tissue-regenerative multipotent stem cells.
iPSC bioprinting for musculoskeletal tissue
Publisher: Elsevier
Date: 2021
Thermally stable and coking resistant CoMo alloy-based catalysts as fuel electrodes for solid oxide electrochemical cells
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8TA04749A
Abstract: Here we report the synthesis of a novel CoMo nanoalloy with controlled structure and composition and in addition, we successfully prevent their agglomerations by constructing a mosaic-like matrix layer to help anchor these nanoparticles.
Cytoskeletal Priming of Mesenchymal Stem Cells to a Medicinal Phenotype
Publisher: Springer Science and Business Media LLC
Date: 06-01-2017
Spatially defined stem cell-laden hydrogel islands for directing endothelial tubulogenesis
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5TB01294E
Abstract: Patterning of encapsulated MSCs for the spatio-temporal guidance of angiogenesis for modelling and design of therapeutic biomaterials.
Biomaterials for Personalized Disease Models
Publisher: Elsevier BV
Date: 09-2021
Enzyme Responsive Inverse Opal Hydrogels
Publisher: Wiley
Date: 31-01-2020
Abstract: Structured color in nature is controlled by nano- and micro-structured interfaces giving rise to a photonic bandgap. This study presents a biomimetic optical material based on polymeric inverse opals that respond to enzyme activity. Polymer colloids provide a template in which acryloyl-functionalized poly(ethylene glycol) is integrated dissolution of the colloids leads to a hydrogel inverse opal that can be lithographically patterned using transfer printing. Incorporating enzyme substrates within the voids provides a material that responds to the presence of proteases through a shift in the optical properties.
Bridging the Gap: From 2D Cell Culture to 3D Microengineered Extracellular Matrices
Publisher: Wiley
Date: 23-11-2015
Peptide Arrays Identify Isoform-Selective Substrates for Profiling Endogenous Lysine Deacetylase Activity
Publisher: American Chemical Society (ACS)
Date: 26-07-2010
DOI: 10.1021/CB100088G
Modifying Porous Silicon with Self-Assembled Monolayers for Biomedical Applications: The Influence of Surface Coverage on Stability and Biomolecule Coupling
Publisher: Wiley
Date: 08-12-2008
Single-step DNA immobilization on antifouling self-assembled monolayers covalently bound to silicon (111)
Publisher: American Chemical Society (ACS)
Date: 14-03-2006
DOI: 10.1021/LA060331A
Abstract: Hydrosilylation of alkenes with epoxide-terminated tri(ethylene oxide) moieties on Si-H surfaces yields homogeneous monolayers for the efficient coupling of biomolecules. The wetting properties of the epoxide-functionalized surface allow for the spotting of solutions of biomolecules, making the surface amenable to microarraying. Immobilization of thiolated DNA was achieved in a single step to fabricate biorecognition interfaces showing the hybridization of complementary DNA at low concentrations and negligible binding of noncomplementary DNA.
Heterotypic tumor models through freeform printing into photostabilized granular microgels
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1BM00574J
Abstract: We report the freeform printing of vessel structures and tumor aggregates within a granular suspension of cells and gelatin methacrylate microgels for modelling cancer progression and metastasis.
Pluripotent stem cell-derived mesenchymal stromal cells improve cardiac function and vascularity after myocardial infarction
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.JCYT.2021.07.016
Abstract: Mesenchymal stromal cells (MSCs) have been shown to improve cardiac function after injury and are the subject of ongoing clinical trials. In this study, the authors tested the cardiac regenerative potential of an induced pluripotent stem cell-derived MSC (iPSC-MSC) population (Cymerus MSCs) in a rat model of myocardial ischemia-reperfusion (I/R). Furthermore, the authors compared this efficacy with bone marrow-derived MSCs (BM-MSCs), which are the predominant cell type in clinical trials. Four days after myocardial I/R injury, rats were randomly assigned to (i) a Cymerus MSC group (n = 15), (ii) a BM-MSC group (n = 15) or (iii) a vehicle control group (n = 14). For cell-treated animals, a total of 5 × 10 One month after cell transplantation, Cymerus MSCs improved LV function (assessed by echocardiography) compared with vehicle and BM-MSCs. Interestingly, Cymerus MSCs enhanced angiogenesis without sustained engraftment or significant impact on infarct scar size. Suggesting safety, Cymerus MSCs had no effect on inducible tachycardia or the ventricular scar heterogeneity that provides a substrate for cardiac re-entrant circuits. The authors here demonstrate that intra-myocardial administration of iPSC-MSCs (Cymerus MSCs) provide better therapeutic effects compared with conventional BM-MSCs in a rodent model of myocardial I/R. Because of its manufacturing scalability, iPSC-MSC therapy offers an exciting opportunity for an "off-the-shelf" stem cell therapy for cardiac repair.
Electrostatic Assembly of Multiarm PEG-Based Hydrogels as Extracellular Matrix Mimics: Cell Response in the Presence and Absence of RGD Cell Adhesive Ligands
Publisher: American Chemical Society (ACS)
Date: 24-02-2023
Rewiring mesenchymal stem cell lineage specification by switching the biophysical microenvironment
Publisher: Springer Science and Business Media LLC
Date: 05-06-2014
DOI: 10.1038/SREP05188
Synthetic Biomaterials to Rival Nature's Complexity—a Path Forward with Combinatorics, High‐Throughput Discovery, and High‐Content Analysis
Publisher: Wiley
Date: 25-08-2017
Abstract: Cells in tissue receive a host of soluble and insoluble signals in a context-dependent fashion, where integration of these cues through a complex network of signal transduction cascades will define a particular outcome. Biomaterials scientists and engineers are tasked with designing materials that can at least partially recreate this complex signaling milieu towards new materials for biomedical applications. In this progress report, recent advances in high throughput techniques and high content imaging approaches that are facilitating the discovery of efficacious biomaterials are described. From microarrays of synthetic polymers, peptides and full-length proteins, to designer cell culture systems that present multiple biophysical and biochemical cues in tandem, it is discussed how the integration of combinatorics with high content imaging and analysis is essential to extracting biologically meaningful information from large scale cellular screens to inform the design of next generation biomaterials.
Peptide microarrays for the discovery of bioactive surfaces that guide cellular processes: a single step azide–alkyne “click” chemistry approach
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4TB00375F
Abstract: Mixed peptide microarrays were formed in a single step using copper-catalyzed “click” chemistry for exploring cell adhesion and differentiation.
A Tunable Tumor Microenvironment through Recombinant Bacterial Collagen-Hyaluronic Acid Hydrogels
Publisher: American Chemical Society (ACS)
Date: 07-06-2022
Abstract: Laboratory models of the tumor microenvironment require control of mechanical and biochemical properties to ensure accurate mimicry of patient disease. In contrast to pure natural or synthetic materials, hybrid approaches that pair recombinant protein fragments with synthetic scaffolding show many advantages. Here we demonstrate production of a recombinant bacterial collagen-like protein (CLP) for thiol-ene pairing to norbornene functionalized hyaluronic acid (NorHA). The resultant hydrogel material shows an adjustable modulus with evidence for strain-stiffening behavior that resembles natural tumor matrices. Cysteine terminated peptide binding motifs are incorporated to adjust the cell-adhesion points. The modular hybrid gel shows good biocompatibility and was demonstrated to control cell adhesion, proliferation, and the invasive properties of MCF7 and MD-MBA-231 breast adenocarcinoma cells. The ease in which multiple structural and bioactive components can be integrated provides a robust framework to form models of the tumor microenvironment for fundamental studies and drug development.
Surveillance of Cancer Stem Cell Plasticity Using an Isoform-Selective Fluorescent Probe for Aldehyde Dehydrogenase 1A1
Publisher: American Chemical Society (ACS)
Date: 25-07-2018
Defined Microenvironments Trigger In Vitro Gastrulation in Human Pluripotent Stem Cells
Publisher: Wiley
Date: 15-12-2022
Abstract: Gastrulation is a stage in embryo development where three germ layers arise to dictate the human body plan. In vitro models of gastrulation have been demonstrated by treating pluripotent stem cells with soluble morphogens to trigger differentiation. However, in vivo gastrulation is a multistage process coordinated through feedback between soluble gradients and biophysical forces, with the multipotent epiblast transforming to the primitive streak followed by germ layer segregation. Here, the authors show how constraining pluripotent stem cells to hydrogel islands triggers morphogenesis that mirrors the stages preceding in vivo gastrulation, without the need for exogenous supplements. Within hours of initial seeding, cells display a contractile phenotype at the boundary, which leads to enhanced proliferation, yes‐associated protein (YAP) translocation, epithelial to mesenchymal transition, and emergence of SRY‐box transcription factor 17 (SOX17) + T/BRACHYURY + cells. Molecular profiling and pathway analysis reveals a role for mechanotransduction‐coupled wingless‐type (WNT) signaling in orchestrating differentiation, which bears similarities to processes observed in whole organism models of development. After two days, the colonies form multilayered aggregates, which can be removed for further growth and differentiation. This approach demonstrates how materials alone can initiate gastrulation, thereby providing in vitro models of development and a tool to support organoid bioengineering efforts.
Theranostic Activity of Ceria-Based Nanoparticles toward Parental and Metastatic Melanoma: 2D vs 3D Models
Publisher: American Chemical Society (ACS)
Date: 02-02-2023
Ceramic Omnidirectional Bioprinting in Cell-Laden Suspensions for the Generation of Bone Analogs
Publisher: MyJove Corporation
Date: 08-08-2022
DOI: 10.3791/63943
Abstract: Structurally, bone tissue is an inorganic-organic composite containing metabolically active cells embedded within a hierarchical, highly mineralized matrix. This organization is challenging to replicate due to the heterogeneous environment of bone. Ceramic omnidirectional bioprinting in cell-suspensions (COBICS) is a microgel-based bioprinting technique that uniquely replicates the mineral and cellular structure of bone. COBICS prints complex, biologically relevant constructs without the need for sacrificial support materials or harsh postprocessing steps (e.g., radiation and high-temperature sintering), which are two of the biggest challenges in the additive manufacturing of bone mimetic constructs. This technique is enabled via the freeform extrusion of a novel calcium phosphate-based ink within a gelatin-based microgel suspension. The yield-stress properties of the suspension allow deposition and support the printed bone structure. UV crosslinking and nanoprecipitation then "lock" it in place. The ability to print nanostructured bone-mimetic ceramics within cell-laden biomaterials provides spatiotemporal control over macro- and micro-architecture and facilitates the real-time fabrication of complex bone constructs in clinical settings.
Defined microenvironments trigger in vitro gastrulation in human pluripotent stem cells
Publisher: Cold Spring Harbor Laboratory
Date: 28-10-2021
DOI: 10.1101/2021.10.28.466327
Abstract: Embryogenesis is orchestrated through local morphogen gradients and endometrial constraints that give rise to the three germ layers in a well-defined assembly. In vitro models of embryogenesis have been demonstrated by treating pluripotent stem cells in adherent or suspension culture with soluble morphogens and small molecules, which leads to tri-lineage differentiation. However, treatment with exogenous agents override the subtle spatiotemporal changes observed in vivo that ultimately underly the human body plan. Here we demonstrate how microconfinement of pluripotent stem cells on hydrogel substrates catalyses gastrulation-like events without the need for supplements. Within six hours of initial seeding, cells at the boundary show elevated cytoskeletal tension and yes-associated protein (YAP) activity, which leads to changes in cell and nuclear morphology, epithelial to mesenchymal transition, and emergence of defined patterns of primitive streak containing SRY-Box Transcription Factor 17 (SOX17) + T/BRACHYURY + cells. Immunofluorescence staining, transcript analysis, and the use of pharmacological modulators reveal a role for mechanotransduction-coupled non-canonical wingless-type (WNT) signalling in promoting epithelial to mesenchymal transition and multilayered organization within the colonies. These microscale gastruloids were removed from the substrate and encapsulated in 3D hydrogels, where biomaterials properties correspond to maintenance and spatial positioning of the primitive streak. Together, this approach demonstrates how materials alone can nurture embryonic gastrulation, thereby providing an in vitro model of early development.
Functionalization of acetylene-terminated monolayers on Si(100) surfaces: A click chemistry approach
Publisher: American Chemical Society (ACS)
Date: 27-07-2007
DOI: 10.1021/LA701035G
Geometric cues for directing the differentiation of mesenchymal stem cells
Publisher: Proceedings of the National Academy of Sciences
Date: 03-2010
Abstract: Significant efforts have been directed to understanding the factors that influence the lineage commitment of stem cells. This paper demonstrates that cell shape, independent of soluble factors, has a strong influence on the differentiation of human mesenchymal stem cells (MSCs) from bone marrow. When exposed to competing soluble differentiation signals, cells cultured in rectangles with increasing aspect ratio and in shapes with pentagonal symmetry but with different subcellular curvature—and with each occupying the same area—display different adipogenesis and osteogenesis profiles. The results reveal that geometric features that increase actomyosin contractility promote osteogenesis and are consistent with in vivo characteristics of the microenvironment of the differentiated cells. Cytoskeletal-disrupting pharmacological agents modulate shape-based trends in lineage commitment verifying the critical role of focal adhesion and myosin-generated contractility during differentiation. Microarray analysis and pathway inhibition studies suggest that contractile cells promote osteogenesis by enhancing c-Jun N-terminal kinase (JNK) and extracellular related kinase (ERK1/2) activation in conjunction with elevated wingless-type (Wnt) signaling. Taken together, this work points to the role that geometric shape cues can play in orchestrating the mechanochemical signals and paracrine/autocrine factors that can direct MSCs to appropriate fates.
Spacing of integrin ligands influences signal transduction in endothelial cells
Publisher: Elsevier BV
Date: 08-2011
Production of Antibacterial Activity and Bone Cell Proliferation by Surface Engineering of Ga‐ or Mn‐Doped Ceria‐Coated Biomedical Titanium Alloy
Publisher: Wiley
Date: 08-05-2022
Abstract: The present work reports a detailed interpretation of the role of Ga and Mn dopants, solid solubility mechanisms, charge compensation mechanisms, intervalence charge transfer, antibacterial performance, and cell attachment and proliferation. Sol–gel undoped and doped (1, 5, and 9 mol%) CeO 2 films are spin‐coated on 3D printed Ti6Al4V biomedical alloy substrates and annealed at 650 °C for 2 h in air. Material characterization includes scanning electron microscopy (SEM), 3D scanning laser confocal microscopy, glancing angle X‐ray diffraction (GAXRD), and X‐ray photoelectron spectroscopy (XPS). In vitro testing includes inhibition of bacterial growth, simulated body fluid (SBF) testing, and cell attachment and proliferation studies. The most significant outcome is that the bioactivity of ceria derives directly from the Ce 3+ concentration, which itself results from solid solubility (substitutional and interstitial) and charge compensation and redox. This challenges the common assumption of the dominance of oxygen vacancies in the performance of ceria. The antibacterial activity is dependent on the type, amount, and valence of the dopant, where opposite trends are observed for gram‐positive Staphylococcus aureus and gram‐negative Escherichia coli bacteria. All of the doped s les result in enhanced cell proliferation, although this is greatest at the lowest dopant concentration. Surface hydroxyapatite formation on the s les is achieved by soaking in SBF at 2 weeks and 1 month.
Geometrically Structured Microtumors in 3D Hydrogel Matrices
Publisher: Wiley
Date: 08-04-2020
Vertical Integration of Cell-Laden Hydrogels with Bioinspired Photonic Crystal Membranes
Publisher: Wiley
Date: 29-10-2018
Geometric guidance of integrin mediated traction stress during stem cell differentiation
Publisher: Elsevier BV
Date: 11-2015
Activating p-Blocking Centers in Perovskite for Efficient Water Splitting
Publisher: Elsevier BV
Date: 12-2018
Porous Chitosan Films Support Stem Cells and Facilitate Sutureless Tissue Repair
Publisher: American Chemical Society (ACS)
Date: 16-08-2019
Controlling cell geometry on substrates of variable stiffness can tune the degree of osteogenesis in human mesenchymal stem cells
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.JMBBM.2014.01.009
Abstract: The physical properties of the extracellular matrix (ECM) play an important role in regulating tissue-specific human mesenchymal stem cell (MSC) differentiation. Protein-coated hydrogels with tunable stiffness have been shown to influence lineage specific gene expression in MSCs. In addition, the control of cell shape - either through changing substrate stiffness or restricting spreading with micropatterning - has proved to be important in guiding the differentiation of MSCs. However, few studies have explored the interplay between these physical cues during MSC lineage specification. Here, we demonstrate geometric control of osteogenesis in MSCs cultured on micropatterned polyacrylamide gels. Cells cultured on fibronectin-coated gels express markers associated with osteogenesis in a stiffness dependent fashion with a maximum at ~30kPa. Controlling the geometry of single cells across the substrate demonstrates elevated osteogenesis when cells are confined to shapes that promote increased cytoskeletal tension. Patterning MSCs across hydrogels of variable stiffness will enable the exploration of the interplay between these physical cues and their relationship with the mechanochemical signals that guide stem cell fate decisions.
Interfacial geometry dictates cancer cell tumorigenicity
Publisher: Springer Science and Business Media LLC
Date: 04-04-2016
DOI: 10.1038/NMAT4610
Abstract: Within the heterogeneous architecture of tumour tissue there exists an elusive population of stem-like cells that are implicated in both recurrence and metastasis. Here, by using engineered extracellular matrices, we show that geometric features at the perimeter of tumour tissue will prime a population of cells with a stem-cell-like phenotype. These cells show characteristics of cancer stem cells in vitro, as well as enhanced tumorigenicity in murine models of primary tumour growth and pulmonary metastases. We also show that interfacial geometry modulates cell shape, adhesion through integrin α5β1, MAPK and STAT activity, and initiation of pluripotency signalling. Our results for several human cancer cell lines suggest that interfacial geometry triggers a general mechanism for the regulation of cancer-cell state. Similar to how a growing tumour can co-opt normal soluble signalling pathways, our findings demonstrate how cancer can also exploit geometry to orchestrate oncogenesis.
Capturing extracellular matrix properties in vitro: Microengineering materials to decipher cell and tissue level processes
Publisher: SAGE Publications
Date: 12-04-2016
Abstract: Rapid advances in biology have led to the establishment of new fields with tremendous translational potential including regenerative medicine and immunoengineering. One commonality to these fields is the need to extract cells for manipulation in vitro however, results obtained in laboratory cell culture will often differ widely from observations made in vivo. To more closely emulate native cell biology in the laboratory, designer engineered environments have proved a successful methodology to decipher the properties of the extracellular matrix that govern cellular decision making. Here, we present an overview of matrix properties that affect cell behavior, strategies for recapitulating important parameters in vitro, and ex les of how these properties can affect cell and tissue level processes, with emphasis on leveraging these tools for immunoengineering.
Freeform printing of heterotypic tumor models within cell-laden microgel matrices
Publisher: Cold Spring Harbor Laboratory
Date: 31-08-2020
DOI: 10.1101/2020.08.30.274654
Abstract: The tissue microenvironment is comprised of a complex assortment of multiple cell types, matrices, membranes and vessel structures. Emulating this complex and often hierarchical organization in vitro has proved a considerable challenge, typically involving segregation of different cell types using layer-by-layer printing or lithographically patterned microfluidic devices. Bioprinting in granular materials is a new methodology with tremendous potential for tissue fabrication. Here, we demonstrate the first ex le of a complex tumor microenvironment that combines direct writing of tumor aggregates, freeform vasculature channels, and a tunable macroporous matrix as a model to studying metastatic signaling. Our photocrosslinkable microgel suspensions yield local stiffness gradients between particles and the intervening space, while enabling the integration of virtually any cell type. Using computational fluid dynamics, we show that removal of a sacrificial Pluronic ink defines vessel-mimetic channel architectures for endothelial cell linings. Pairing this vasculature with 3D printing of melanoma aggregates, we find that tumor cells within proximity migrated into the prototype vasculature. Together, the integration of perfusable channels with multiple spatially defined cell types provides new avenues for modelling development and disease, with scope for fundamental research and drug development.
Gallium Nanodroplets are Anti-Inflammatory without Interfering with Iron Homeostasis
Publisher: American Chemical Society (ACS)
Date: 25-05-2022
Abstract: Gallium (Ga) compounds, as the source of Ga ions (Ga
Structural aspects controlling the mechanical and biological properties of tough, double network hydrogels
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.ACTBIO.2021.10.044
Abstract: Anticipating an increasing demand for hybrid double network (DN) hydrogels in biomedicine and biotechnology, this study evaluated the effects of each network on the mechanical and biological properties. Polyethylene glycol (PEG) (meth)acrylate hydrogels with varied monomer molecular weights and architectures (linear vs. 4-arm) were produced with and without an added ionically bonded alginate network and their mechanical properties were characterized using compression testing. The results showed that while some mechanical properties of PEG single network (SN) hydrogels decreased or changed negligibly with increasing molecular weight, the compressive modulus, strength, strain to failure, and toughness of DN hydrogels all significantly increased with increased PEG monomer molecular weight. At a fixed molecular weight (10 kDa), 4-arm PEG SN hydrogels exhibited better overall mechanical performance however, this benefit was diminished for the corresponding DN hydrogels with comparable strength and toughness and lower strain to failure for the 4-arm case. Regardless of the PEG monomer structure, the alginate network made a relatively larger contribution to the overall DN mechanical properties when the covalent PEG network was looser with a larger mesh size (e.g., for larger monomer molecular weight and/or linear architecture) which presumably enabled more ionic crosslinking. Considering the biological performance, adipose derived stem cell cultures demonstrated monotonically increasing cell area and Yes-associated protein related mechanosensing with increasing amounts of alginate from 0 to 2 wt.%, demonstrating the possibility for using DN hydrogels in guiding musculoskeletal differentiation. These findings will be useful to design suitable hydrogels with controllable mechanical and biological properties for mechanically demanding applications. STATEMENT OF SIGNIFICANCE: Hydrogels are widely used in commercial applications, and recently developed hybrid double network hydrogels have enhanced strength and toughness that will enable further expansion into more mechanically demanding applications (e.g., medical implants, etc.). The significance of this work is that it uncovers some key principles regarding monomer molecular weight, architecture, and concentration for developing strong and tough hybrid double network hydrogels that would not be predicted from their single network counterparts or a linear combination of the two networks. Additionally, novel insight is given into the biological performance of hybrid double network hydrogels in the presence of adipose derived stem cell cultures which suggests new scope for using double network hydrogels in guiding musculoskeletal differentiation.
In situ formation of osteochondral interfaces through “bone-ink” printing in tailored microgel suspensions
Publisher: Elsevier BV
Date: 2023
DOI: 10.1016/J.ACTBIO.2022.08.052
Abstract: Osteochondral tissue has a complex hierarchical structure spanning subchondral bone to articular cartilage. Biomaterials approaches to mimic and repair these interfaces have had limited success, largely due to challenges in fabricating composite hard-soft interfaces with living cells. Biofabrication approaches have emerged as attractive methods to form osteochondral analogues through additive assembly of hard and soft components. We have developed a unique printing platform that is able to integrate soft and hard materials concurrently through freeform printing of mineralized constructs within tunable microgel suspensions containing living cells. A library of microgels based on gelatin were prepared, where the stiffness of the microgels and a liquid "filler" phase can be tuned for bioprinting while simultaneously directing differentiation. Tuning microgel stiffness and filler content differentially directs chondrogenesis and osteogenesis within the same construct, demonstrating how this technique can be used to fabricate osteochondral interfaces in a single step. Printing of a rapidly setting calcium phosphate cement, so called "bone-ink" within a cell laden suspension bath further guides differentiation, where the cells adjacent to the nucleated hydroxyapatite phase undergo osteogenesis with cells in the surrounding medium undergoing chondrogenesis. In this way, bone analogues with hierarchical structure can be formed within cell-laden gradient soft matrices to yield multiphasic osteochondral constructs. This technique provides a versatile one-pot biofabrication approach without harsh post-processing which will aid efforts in bone disease modelling and tissue engineering. STATEMENT OF SIGNIFICANCE: This paper demonstrates the first ex le of a biofabrication approach to rapidly form osteochondral constructs in a single step under physiological conditions. Key to this advance is a tunable suspension of extracellular matrix microgels that are packed together with stem cells, providing a unique and modular scaffolding for guiding the simultaneous formation of bone and cartilage tissue. The physical properties of the suspension allow direct writing of a ceramic "bone-ink", resulting in an ordered structure of microscale hydrogels, living cells, and bone mimics in a single step. This platform reveals a simple approach to making complex skeletal tissue for disease modelling, with the possibility of repairing and replacing bone-cartilage interfaces in the clinic using a patient's own cells.
Melanoma topology reveals a stem-like phenotype that promotes angiogenesis
Publisher: American Association for the Advancement of Science (AAAS)
Date: 06-10-2017
Abstract: Melanoma topology promotes a stem cell phenotype with the propensity to facilitate new vessel growth.
Smart tissue culture: in situ monitoring of the activity of protease enzymes secreted from live cells using nanostructured photonic crystals
Publisher: American Chemical Society (ACS)
Date: 21-04-2009
DOI: 10.1021/NL900283J
Abstract: Monitoring enzyme secretion in tissue culture has proved challenging because to date the activity cannot be continuously measured in situ. In this Letter, we present a solution using biopolymer loaded photonic crystals of anodized silicon. Shifts in the optical response by proteolytic degradation of the biopolymer provide label-free sensing with unprecedented low detection limits (1 pg) and calculation of kinetic parameters. The enhancement in sensitivity relative to previous photonic crystal sensors constitutes a change in the sensing paradigm because here the entire pore space is responsive to the secreted enzyme rather than just the pore walls. In situ monitoring is demonstrated by detecting secretion of matrix metalloprotease 9 from stimulated human macrophages.
Corrigendum to ‘Structural aspects controlling the mechanical and biological properties of tough, double network hydrogels’ [Acta Biomaterialia 138 (2022) 301–312]
Publisher: Elsevier BV
Date: 03-2023
Patterned porous silicon photonic crystals with modular surface chemistry for spatial control of neural stem cell differentiation
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C5NR08327C
Abstract: Patterned gold and photonic crystals with modular surface chemistry direct neural stem cell diffrentiation.
Stabilizing Double Perovskite for Effective Bifunctional Oxygen Electrocatalysis in Alkaline Conditions
Publisher: American Chemical Society (ACS)
Date: 25-07-2017
Hybrid lipid bilayers in nanostructured silicon: A biomimetic mesoporous scaffold for optical detection of cholera toxin
Publisher: Royal Society of Chemistry (RSC)
Date: 2007
DOI: 10.1039/B702762A
Abstract: Cholera toxin levels are optically detected by affinity capture within hybrid lipid bilayer membranes formed in the nanostructures of porous silicon photonic crystals.
Porous silicon based narrow line-width rugate filters
Publisher: Elsevier BV
Date: 02-2007
Gas-modulating microcapsules for spatiotemporal control of hypoxia
Publisher: Proceedings of the National Academy of Sciences
Date: 11-04-2023
Abstract: Oxygen is a vital molecule involved in regulating development, homeostasis, and disease. The oxygen levels in tissue vary from 1 to 14% with deviations from homeostasis impacting regulation of various physiological processes. In this work, we developed an approach to encapsulate enzymes at high loading capacity, which precisely controls the oxygen content in cell culture. Here, a single microcapsule is able to locally perturb the oxygen balance, and varying the concentration and distribution of matrix-embedded microcapsules provides spatiotemporal control. We demonstrate attenuation of hypoxia signaling in populations of stem cells, cancer cells, endothelial cells, cancer spheroids, and intestinal organoids. Varying capsule placement, media formulation, and timing of replenishment yields tunable oxygen gradients, with concurrent spatial growth and morphogenesis in a single well. Capsule containing hydrogel films applied to chick chorioallantoic membranes encourages neovascularization, providing scope for topical treatments or hydrogel wound dressings. This platform can be used in a variety of formats, including deposition in hydrogels, as granular solids for 3D bioprinting, and as injectable biomaterials. Overall, this platform’s simplicity and flexibility will prove useful for fundamental studies of oxygen-mediated processes in virtually any in vitro or in vivo format, with scope for inclusion in biomedical materials for treating injury or disease.
Hierarchical assembly of tryptophan zipper peptides into stress-relaxing bioactive hydrogels
Publisher: Springer Science and Business Media LLC
Date: 23-10-2023
Optimisation of nanostructured porous silicon surface chemistry towards biophotonic sensors
Publisher: IEEE
Date: 2006
Materials control of the epigenetics underlying cell plasticity
Publisher: Springer Science and Business Media LLC
Date: 29-09-2020
Synthetic Bone‐Like Structures Through Omnidirectional Ceramic Bioprinting in Cell Suspensions
Publisher: Wiley
Date: 20-01-2021
Simultaneous cell traction and growth measurements using light
Publisher: Wiley
Date: 07-11-2018
Abstract: Characterizing the effects of force fields generated by cells on proliferation, migration and differentiation processes is challenging due to limited availability of nondestructive imaging modalities. Here, we integrate a new real‐time traction stress imaging modality, Hilbert phase dynamometry (HPD), with spatial light interference microscopy (SLIM) for simultaneous monitoring of cell growth during differentiation processes. HPD uses holographic principles to extract displacement fields from chemically patterned fluorescent grid on deformable substrates. This is converted into forces by solving an elasticity inverse problem. Since HPD uses the epi‐fluorescence channel of an inverted microscope, cellular behavior can be concurrently studied in transmission with SLIM. We studied the differentiation of mesenchymal stem cells (MSCs) and found that cells undergoing osteogenesis and adipogenesis exerted larger and more dynamic stresses than their precursors, with MSCs developing the smallest forces and growth rates. Thus, we develop a powerful means to study mechanotransduction during dynamic processes where the matrix provides context to guide cells toward a physiological or pathological outcome.
Magnetic Nanofibrous Hydrogels for Dynamic Control of Stem Cell Differentiation
Publisher: American Chemical Society (ACS)
Date: 29-08-2023
Counting growth factors in single cells with infrared quantum dots to measure discrete stimulation distributions
Publisher: Springer Science and Business Media LLC
Date: 22-02-2019
DOI: 10.1038/S41467-019-08754-5
Abstract: The distribution of single-cell properties across a population of cells can be measured using erse tools, but no technology directly quantifies the biochemical stimulation events regulating these properties. Here we report digital counting of growth factors in single cells using fluorescent quantum dots and calibrated three-dimensional deconvolution microscopy (QDC-3DM) to reveal physiologically relevant cell stimulation distributions. We calibrate the fluorescence intensities of in idual compact quantum dots labeled with epidermal growth factor (EGF) and demonstrate the necessity of near-infrared emission to overcome intrinsic cellular autofluoresence at the single-molecule level. When applied to human triple-negative breast cancer cells, we observe proportionality between stimulation and both receptor internalization and inhibitor response, reflecting stimulation heterogeneity contributions to intrinsic variability. We anticipate that QDC-3DM can be applied to analyze any peptidic ligand to reveal single-cell correlations between external stimulation and phenotypic variability, cell fate, and drug response.
Quantitative phase imaging reveals matrix stiffness-dependent growth and migration of cancer cells
Publisher: Springer Science and Business Media LLC
Date: 22-01-2019
DOI: 10.1038/S41598-018-36551-5
Abstract: Cancer progression involves complex signals within the tumor microenvironment that orchestrate proliferation and invasive processes. The mechanical properties of the extracellular matrix (ECM) within this microenvironment has been demonstrated to influence growth and the migratory phenotype that precedes invasion. Here we present the integration of a label-free quantitative phase imaging technique, spatial light interference microscopy (SLIM)—with protein-conjugated hydrogel substrates—to explore how the stiffness of the ECM influences melanoma cells of varying metastatic potential. Melanoma cells of high metastatic potential demonstrate increased growth and velocity characteristics relative to cells of low metastatic potential. Cell velocity in the highly metastatic population shows a relative stability at higher matrix stiffness suggesting adoption of migratory routines that are independent of mechanics to facilitate invasion. The use of SLIM and engineered substrates provides a new approach to characterize the invasive properties of live cells as a function of microenvironment parameters. This work provides fundamental insight into the relationship between growth, migration and metastatic potential, and provides a new tool for profiling cancer cells for clinical grading and development of patient-specific therapeutic regimens.
Temporal Modulation of Stem Cell Activity Using Magnetoactive Hydrogels
Publisher: Wiley
Date: 08-06-2016
Peptide-modified optical filters for detecting protease activity
Publisher: American Chemical Society (ACS)
Date: 31-10-2007
DOI: 10.1021/NN700141N
Abstract: The organic derivatization of silicon-based nanoporous photonic crystals is presented as a method to immobilize peptides for the detection of protease enzymes in solution. A narrow-line-width rugate filter, a one-dimensional photonic crystal, is fabricated that exhibits a high-reflectivity optical resonance that is sensitive to small changes in the refractive index at the pore walls. To immobilize peptide in the pore of the photonic crystal, the hydrogen-terminated silicon surface was first modified with the alkene 10-succinimidyl undecenoate via hydrosilylation. The monolayer with the succinimide ester moiety at the distal end served the dual function of protecting the underlying silicon from oxidation as well as providing a surface suitable for subsequent derivatization with amines. The surface was further modified with 1-aminohexa(ethylene glycol) (EG(6)) to resist nonspecific adsorption of proteins common in complex biological s les. The distal hydroxyl of the EG(6) is activated using the solid-phase coupling reagent disuccinimidyl carbonate for selective immobilization of peptides as protease recognition elements. X-ray photoelectron spectroscopy analysis reveals high activation and coupling efficiency at each stage of the functionalization. Exposure of the peptide-modified crystals to the protease subtilisin in solution causes a change in the refractive index, resulting in a shift of the resonance to shorter wavelengths, indicating cleavage of organic material within the pores. The lowest detected concentration of enzyme was 37 nM (7.4 pmol in 200 microL).
Gas modulating microcapsules for spatiotemporal control of hypoxia
Publisher: Cold Spring Harbor Laboratory
Date: 04-09-2022
DOI: 10.1101/2022.09.02.506302
Abstract: Oxygen is a vital molecule involved in regulating development, homeostasis, and disease. The oxygen levels in tissue vary from 1 to 8% with deviations having major biological consequences. In this work, we developed an approach to encapsulate enzymes and nanozymes, at an unprecedented loading capacity, which precisely controls the oxygen content in cell culture. Here, a single microcapsule is able to locally perturb the oxygen balance, and varying the concentration and distribution of matrix embedded microcapsules provides spatiotemporal control. We demonstrate attenuation of hypoxia signaling in populations of stem cells, cancer cells, endothelial cells, and cancer spheroids. Capsule containing hydrogel films applied to chick chorioallantoic membranes encourage neovascularization, providing scope for topical treatments or hydrogel wound dressings. We further demonstrate versatility by loading capsules with ceria nanorods as “nanozymes” to modulate active oxygen species with potential as a cytoprotective treatment. The approach can be used in multiple formats, including deposition in hydrogels, as granular solids for 3D bioprinting, and as injectable biomaterials. Overall, this platform’s simplicity and flexibility will prove useful for fundamental studies of oxygen-mediated processes in virtually any in vitro or in vivo format, with scope for inclusion in biomedical materials where controlling hypoxia may be clinically advantageous.
Hydrogel Microtumor Arrays to Evaluate Nanotherapeutics
Publisher: Wiley
Date: 28-11-2022
Abstract: Nanoparticle drug formulations have many advantages for cancer therapy due to benefits in targeting selectivity, lack of systemic toxicity, and increased drug concentration in the tumor microenvironment after delivery. However, the promise of nanomedicine is limited by preclinical models that fail to accurately assess new drugs before entering human trials. In this work a new approach to testing nanomedicine using a microtumor array formed through hydrogel micropatterning is demonstrated. This technique allows partitioning of heterogeneous cell states within a geometric pattern—where boundary regions of curvature prime the stem cell‐like fraction—allowing to simultaneously probe drug uptake and efficacy in different cancer cell fractions with high reproducibility. Using melanoma cells of different metastatic potential, a relationship between stem fraction and nanoparticle uptake is discovered. Deformation cytometry reveals that the stem cell‐like population exhibits a more mechanically deformable cell membrane. Since the stem fraction in a tumor is implicated in drug resistance, recurrence, and metastasis, the findings suggest that nanoparticle drug formulations are well suited for targeting this dangerous cell population in cancer therapy.
Porous chitosan adhesives with L-DOPA for enhanced photochemical tissue bonding
Publisher: Elsevier BV
Date: 2020
Computational Curriculum for MatSE Undergraduates
Publisher: ASEE Conferences
Date: 2017
DOI: 10.18260/1-2--28060
The structural fate of lipid nanoparticles in the extracellular matrix
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/C9MH00835G
Abstract: Hydrogels cause unilamellar liposomes to transform into aggregates of multilamellar structures through an osmotic effect.
Anti-inflammatory ω-3 endocannabinoid epoxides
Publisher: Proceedings of the National Academy of Sciences
Date: 07-07-2017
Abstract: The health benefits of ω-3 fatty acids are mediated, in part, through metabolic conversion to bioactive epoxides. Here we detail the discovery and initial characterization of naturally occurring ω-3–derived endocannabinoid epoxides that are formed via enzymatic oxidation of ω-3 endocannabinoids by cytochrome P450s. These dual functional ω-3 endocannabinoid epoxides are anti-inflammatory and vasodilatory and reciprocally modulate platelet aggregation. By virtue of their physiological properties, they are expected to play important roles in neuroinflammation and in cerebrovascular diseases such as stroke.
Effects of Atmospheric Ozone on Microarray Data Quality
Publisher: American Chemical Society (ACS)
Date: 15-07-2003
DOI: 10.1021/AC034241B
Abstract: A data anomaly was observed that affected the uniformity and reproducibility of fluorescent signal across DNA microarrays. Results from experimental sets designed to identify potential causes (from microarray production to array scanning) indicated that the anomaly was linked to a batch process further work allowed us to localize the effect to the posthybridization array stringency washes. Ozone levels were monitored and highly correlated with the batch effect. Controlled exposures of microarrays to ozone confirmed this factor as the root cause, and we present data that show susceptibility of a class of cyanine dyes (e.g., Cy5, Alexa 647) to ozone levels as low as 5-10 ppb for periods as short as 10-30 s. Other cyanine dyes (e.g., Cy3, Alexa 555) were not significantly affected until higher ozone levels (> 100 ppb). To address this environmental effect, laboratory ozone levels should be kept below 2 ppb (e.g., with filters in HVAC) to achieve high quality microarray data.
Combinatorial Discovery of Defined Substrates That Promote a Stem Cell State in Malignant Melanoma
Publisher: American Chemical Society (ACS)
Date: 26-04-2017
Mechanochemical functionalization of disulfide linked hydrogels
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6MH00091F
Abstract: Poly(ethylene glycol) hydrogels with disulfide linkages are functionalized through applied force.
Engineered Biomaterials for Developing the Next Generation of In Vitro Tumor Models
Publisher: Wiley
Date: 06-2023
Directing stem cell fate on hydrogel substrates by controlling cell geometry, matrix mechanics and adhesion ligand composition
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.BIOMATERIALS.2013.07.074
Abstract: There is a dynamic relationship between physical and biochemical signals presented in the stem cell microenvironment to guide cell fate determination. Model systems that modulate cell geometry, substrate stiffness or matrix composition have proved useful in exploring how these signals influence stem cell fate. However, the interplay between these physical and biochemical cues during differentiation remains unclear. Here, we demonstrate a microengineering strategy to vary single cell geometry and the composition of adhesion ligands - on substrates that approximate the mechanical properties of soft tissues - to study adipogenesis and neurogenesis in adherent mesenchymal stem cells. Cells cultured in small circular islands show elevated expression of adipogenesis markers while cells that spread in anisotropic geometries tend to express elevated neurogenic markers. Arraying different combinations of matrix protein in a myriad of 2D and pseudo-3D geometries reveals optimal microenvironments for controlling the differentiation of stem cells to these "soft" lineages without the use of media supplements.
Magnetic Nanocomposite Hydrogels for Directing Myofibroblast Activity in Adipose‐Derived Stem Cells
Publisher: Wiley
Date: 22-02-2021
Production of complex nucleic acid libraries using highly parallel in situ oligonucleotide synthesis
Publisher: Springer Science and Business Media LLC
Date: 18-11-2004
DOI: 10.1038/NMETH724
Abstract: Generation of complex libraries of defined nucleic acid sequences can greatly aid the functional analysis of protein and gene function. Previously, such studies relied either on in idually synthesized oligonucleotides or on cellular nucleic acids as the starting material. As each method has disadvantages, we have developed a rapid and cost-effective alternative for construction of small-fragment DNA libraries of defined sequences. This approach uses in situ microarray DNA synthesis for generation of complex oligonucleotide populations. These populations can be recovered and either used directly or immortalized by cloning. From a single microarray, a library containing thousands of unique sequences can be generated. As an ex le of the potential applications of this technology, we have tested the approach for the production of plasmids encoding short hairpin RNAs (shRNAs) targeting numerous human and mouse genes. We achieved high-fidelity clone retrieval with a uniform representation of intended library sequences.
Silicon-based mesoporous photonic crystals: Towards single cell optical biosensors
Publisher: SPIE
Date: 20-08-2009
DOI: 10.1117/12.826133
Multimodal Assessment of Mesenchymal Stem Cell Therapy for Diabetic Vascular Complications
Publisher: Ivyspring International Publisher
Date: 2017
DOI: 10.7150/THNO.19547
Matrix Composition and Mechanics Direct Proangiogenic Signaling from Mesenchymal Stem Cells
Publisher: Mary Ann Liebert Inc
Date: 10-2014
Micro-Engineered Models of Development Using Induced Pluripotent Stem Cells
Publisher: Frontiers Media SA
Date: 29-11-2019
Physicochemical Tools for Visualizing and Quantifying Cell-Generated Forces
Publisher: American Chemical Society (ACS)
Date: 12-06-2020
Antibody Self-Assembly Maximizes Cytoplasmic Immunostaining Accuracy of Compact Quantum Dots
Publisher: American Chemical Society (ACS)
Date: 17-06-2021
Force-mediated molecule release from double network hydrogels
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1CC02726C
Abstract: Mechanochemical release of molecules through a retro Diels–Alder reaction is demonstrated within double network hydrogels.
Formation of tetra(ethylene oxide) terminated Si - C linked monolayers and their derivatization with glycine: An example of a generic strategy for the immobilization of biomolecules on silicon
Publisher: American Chemical Society (ACS)
Date: 28-09-2005
DOI: 10.1021/LA051191S
Abstract: Surface modification with oligo(ethylene oxide) functionalized monolayers terminated with reactive headgroups constitutes a powerful strategy to provide specific coupling of biomolecules with simultaneous protection from nonspecific adsorption on surfaces for the preparation of biorecognition interfaces. To date, oligo(ethylene oxide) functionalized monolayer-forming molecules which can be activated for attachment of biomolecules but which can selectively form monolayers onto hydrogen terminated silicon have yet to be developed. Here, self-assembled monolayers (SAMs) containing tetra(ethylene oxide) moieties protected with tert-butyl dimethylsilyl groups were formed by thermal hydrosilylation of alkenes with single-crystal Si(111)-H. The protection group was used to avoid side reactions with the hydride terminated silicon surface. Monolayer formation was carried out using solutions of the alkene in the high-boiling-point solvent 1,3,5-triethylbenzene. The protecting group was removed under very mild acidic conditions to yield a free hydroxyl functionality, a convenient surface moiety for coupling of biological entities via carbamate bond formation. The chemical composition and structure of the monolayers before and after deprotection were characterized by X-ray photoelectron spectroscopy (XPS) and X-ray reflectometry. To demonstrate the utility of this surface for covalent modification, two reagents were compared and contrasted for their ability to activate the surface hydroxyl groups for coupling of free amines, carbonyl diimidazole (CDI), and disuccinimidyl carbonate (DSC). Analysis of XP spectra before and after activation by CDI or DSC, and after subsequent reaction with glycine, provided quantitative information on the extent of activation and overall coupling efficiencies. CDI activated surfaces gave poor coupling yields under various conditions, whereas DSC mediated activation followed by aminolysis at neutral pH was found to be an efficient method for the immobilization of amines on tetra(ethylene oxide) modified surfaces.
Targeting cell plasticity for regeneration: From in vitro to in vivo reprogramming
Publisher: Elsevier BV
Date: 2020
Evaluation of the Immune Response to Chitosan-graft-poly(caprolactone) Biopolymer Scaffolds
Publisher: American Chemical Society (ACS)
Date: 23-05-2023
Patterned substrates modulate growth and dynamics of 3D cellular systems
Publisher: Cold Spring Harbor Laboratory
Date: 08-05-2019
DOI: 10.1101/632034
Abstract: The development of 3D cellular architectures during development and pathological processes involves intricate migratory patterns that are modulated by genetics and the surrounding microenvironment. The substrate composition of cell cultures has been demonstrated to influence growth, proliferation, and migration in 2D. Here we study the growth and dynamics of mouse embryonic fibroblast (MEF) cultures patterned in a tissue sheet which then exhibits 3D growth. Using gradient light interference microscopy (GLIM), a label-free quantitative phase imaging approach, we explored the influence of geometry on cell growth patterns and rotational dynamics. We apply, for the first time to our knowledge, dispersion-relation phase spectroscopy (DPS) in polar coordinates to generate the radial and rotational cell mass-transport. Our data show that cells cultured on engineered substrates undergo rotational transport in a radially independent manner and exhibit faster vertical growth than the control, unpatterned cells. The use of GLIM and polar DPS provides a novel quantitative approach to studying the effects of spatially patterned substrates on cell motility and growth.
Cellular signaling
Publisher: Elsevier
Date: 2023
Matrix directed adipogenesis and neurogenesis of mesenchymal stem cells derived from adipose tissue and bone marrow
Publisher: Elsevier BV
Date: 09-2016
Introducing distinctly different chemical functionalities onto the internal and external surfaces of mesoporous materials
Publisher: Wiley
Date: 18-03-2008
Geometric regulation of histone state directs melanoma reprogramming
Publisher: Cold Spring Harbor Laboratory
Date: 11-12-2019
DOI: 10.1101/872226
Abstract: Malignant melanoma displays a high degree of cellular plasticity during disease progression, making classification of the heterogeneous population and selection of an appropriate therapy challenging. Signals in the tumor microenvironment are believed to influence melanoma plasticity through changes in the epigenetic state to guide dynamic differentiation and de-differentiation events that underlie tumorigenicity and dissemination. Here we uncover a relationship between geometric features at perimeter regions of multicellular melanoma aggregates, and reprogramming to a stem cell-like melanoma initiating cell (MIC) through histone marks H3K4Me2 and H3K9Ac. Using an in vitro tumor microengineering approach, we find concurrent expression of molecular MIC markers and spatial enrichment of these histone modifications at perimeter features. Chromatin immunoprecipitation and sequencing analysis demonstrates broad regulation of genes associated with SOX-, ETS-, and USF-families. SOX10 and PRDM14, transcriptional regulators with a putative role in several cancers, overlap with H3K9Ac and show elevated expression in cells along regions of perimeter curvature. siRNA knockdown of the epigenetic modifier PRDM14 abolishes the MIC phenotype suggesting a role in regulating melanoma heterogeneity. Our results suggest mechanotransduction at the periphery of melanoma tumors may orchestrate the activity of epigenetic modifiers to regulate histone state, cellular plasticity, and tumorigenicity.
Organic modification of mesoporous silicon rugate filters: The influence of nanoarchitecture on optical behaviour
Publisher: Inderscience Publishers
Date: 2008
Influence of Biophysical Parameters on Maintaining the Mesenchymal Stem Cell Phenotype
Publisher: American Chemical Society (ACS)
Date: 06-03-2015
DOI: 10.1021/AB500003S
Click chemistry in mesoporous materials: Functionalization of porous silicon rugate filters
Publisher: American Chemical Society (ACS)
Date: 02-05-2008
DOI: 10.1021/LA800435D
The effect of mesenchymal stem cell shape on the maintenance of multipotency
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.BIOMATERIALS.2013.02.029
Abstract: Human mesenchymal stem cells (MSCs) have broad therapeutic potential due to their ability to differentiate into multiple cell types. However, when cultured ex vivo MSCs will spontaneously differentiate and have been shown to lose multipotency after prolonged passaging. Cell culture conditions that promote maintenance of multipotency during in vitro expansion are a critical need to fully realize the therapeutic potential of MSCs. Here we show that by confining MSCs to small islands, we can restrict inappropriate lineage specification and enhance the expression of mesenchymal stem cell markers Stro-1 and Endoglin. Even when released from the islands and reseeded, cells previously cultured in patterns maintain higher expression of MSC markers compared to cells cultured on plastic, while maintaining their ability to differentiate into adipocytes and osteoblasts. Exposure of non-patterned cells to inhibitors of myosin and Rho-associated protein kinase (ROCK) leads to increased expression of stem cell markers. Our findings suggest that maintenance of MSC "stemness" requires a low state of actomyosin contractility. This work will prove useful in the development of culture conditions for the maintenance of multipotent MSCs in vitro and for the design of niche-mimetic biomaterials.
Substrate independent assembly of optical structures guided by biomolecular interactions
Publisher: American Chemical Society (ACS)
Date: 05-11-2010
DOI: 10.1021/AM1007084
Abstract: The chip-scale integration of optical components is crucial for technologies as erse as optical communications, optoelectronics displays, and photovoltaics. However, the realization of integrated optical devices from discrete components is often h ered by the lack of a universal substrate for achieving monolithic integration and by incompatibilities between materials. Emergent technologies such as chip-scale biophotonics, organic optoelectronics, and optofluidics present a host of new challenges for optical device integration, which cannot be solved with existing bonding techniques. Here, we report a new method for substrate independent integration of dissimilar optical components by way of biological recognition-directed assembly. Bonding in this scheme is achieved by locally modifying the substrate with a protein receptor and the optical component with a biomolecular ligand or vice versa. The key features of this new technology include substrate independent assembly, cross-platform vertical scale integration, and selective registration of components based on complementary biomolecular interactions.
Effects of substrate patterning on cellular spheroid growth and dynamics measured by gradient light interference microscopy (GLIM)
Publisher: Wiley
Date: 03-10-2019
Geometric regulation of histone state directs melanoma reprogramming
Publisher: Springer Science and Business Media LLC
Date: 03-07-2020
DOI: 10.1038/S42003-020-1067-1
Abstract: Malignant melanoma displays a high degree of cellular plasticity during disease progression. Signals in the tumor microenvironment are believed to influence melanoma plasticity through changes in the epigenetic state to guide dynamic differentiation and de-differentiation. Here we uncover a relationship between geometric features at perimeter regions of melanoma aggregates, and reprogramming to a stem cell-like state through histone marks H3K4Me2 and H3K9Ac. Using an in vitro tumor microengineering approach, we find spatial enrichment of these histone modifications with concurrent expression of stemness markers. The epigenetic modifier PRDM14 overlaps with H3K9Ac and shows elevated expression in cells along regions of perimeter curvature. siRNA knockdown of PRDM14 abolishes the MIC phenotype suggesting a role in regulating melanoma heterogeneity. Our results suggest mechanotransduction at the periphery of melanoma aggregates may orchestrate the activity of epigenetic modifiers to regulate histone state, cellular plasticity, and tumorigenicity.
The importance of surface chemistry in mesoporous materials: Lessons from porous silicon biosensors
Publisher: Royal Society of Chemistry (RSC)
Date: 2009
DOI: 10.1039/B815449J
Abstract: The ease of fabricating high quality photonic crystals from porous silicon and its biocompatibility have inspired the conception of various biosensing schemes using this material. However, the instability of porous silicon has significantly slowed progress in this area. Here we discuss the potential of different porous silicon photonic crystals for biosensing in the context of its surface chemistry and nanostructure, both of which need to be optimized to obtain sensitive and stable devices. Of particular promise are recent approaches that use porous silicon as sensors for enzymatic activity, for cell capture and concentration devices.
High throughput strategies for the design, discovery, and analysis of biomaterials
Publisher: Elsevier BV
Date: 04-2016
Matrix Mechanics Influence Fibroblast–Myofibroblast Transition by Directing the Localization of Histone Deacetylase 4
Publisher: Springer Science and Business Media LLC
Date: 18-07-2017
Interfacial Curvature in Confined Coculture Directs Stromal Cell Activity with Spatial Corralling of Pancreatic Cancer Cells
Publisher: Wiley
Date: 22-03-2021
Abstract: Interfacial cues in the tumor microenvironment direct the activity and assembly of multiple cell types. Pancreatic cancer, along with breast and prostate cancers, is enriched with cancer‐associated fibroblasts (CAFs) that activate to coordinate the deposition of the extracellular matrix, which can comprise over 90% of the tumor mass. While it is clear that matrix underlies the severity of the disease, the relationship between stromal‐tumor cell assembly and cell‐matrix dynamics remains elusive. Micropatterned hydrogels deconstruct the interplay between matrix stiffness and geometric confinement, guiding heterotypic cell populations and matrix assembly in pancreatic cancer. Interfacial cues at the perimeter of microislands guide CAF migration and direct cancer cell assembly. Computational modeling shows curvature‐stress dependent cellular localization for cancer and CAFs in coculture. Regions of convex curvature enhance edge stress that activates a myofibroblast phenotype in the CAFs with migration and increased collagen I deposition, ultimately leading to a central “corralling” of cancer cells. Inhibiting mechanotransduction pathways decreases CAF activation and the associated corralling phenotype. Together, this work reveals how interfacial biophysical cues underpin aspects of stromal desmoplasia, a hallmark of disease severity and chemoresistance in the pancreatic, breast, and prostate cancers, thereby providing a tool to expand stroma‐targeting therapeutic strategies.
Biofunctionalization of free-standing porous silicon films for self-assembly of photonic devices
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C1SM06651J
Epidermal mechano-acoustic sensing electronics for cardiovascular diagnostics and human-machine interfaces
Publisher: American Association for the Advancement of Science (AAAS)
Date: 04-11-2016
Abstract: Researchers report advances in materials and designs for skin-integrated devices capable of measuring acoustic signatures.
Forming antifouling organic multilayers on porous silicon rugate filters towards in vivo/ex vivo biophotonic devices
Publisher: Wiley
Date: 15-10-2007
Simultaneous cell traction and growth measurements using light
Publisher: Cold Spring Harbor Laboratory
Date: 20-10-2017
DOI: 10.1101/206649
Abstract: Understanding cell mechanotransduction is important for discerning matrix structure-cell function relationships underlying health and disease. Despite the crucial role of mechanochemical signaling in phenomena such as cell migration, proliferation, and differentiation, measuring the cell-generated forces at the interface with the extracellular matrix during these biological processes remains challenging. An ideal method would provide continuous, non-destructive images of the force field applied by cells, over broad spatial and temporal scales, while simultaneously revealing the cell biological process under investigation. Toward this goal, we present the integration of a new real-time traction stress imaging modality, Hilbert phase dynamometry (HPD), with the technique of spatial light interference microscopy (SLIM) for label free monitoring of cell growth. HPD relies on extracting the displacement field in a deformable substrate, which is chemically patterned with a fluorescent grid. The displacements introduced by the cell are captured by the phase of the periodic signal associated with the grid, borrowing concepts from holography. The displacement field is uniquely converted into forces by solving an elasticity inverse problem. Because the measurement of displacement only uses the epi-fluorescence channel of an inverted microscope, we can simultaneously achieve measurements in transmission. We performed SLIM and extracted cell mass on the same field of view in addition to the measured displacement field. We used this technique to study mesenchymal stem cells and found that cells undergoing osteogenesis and adipogenesis exerted larger and more dynamic stresses than their precursor. Our results indicate that the MSCs develop the smallest forces and growth rates. We anticipate that simultaneous cell growth and traction measurements will improve our understanding of mechanotransduction, particularly during dynamic processes where the matrix properties provide context to guide cells towards a physiological or pathological outcome, e.g., tissue morphogenesis, or cancer metastasis.
Author Correction: Quantitative phase imaging reveals matrix stiffness-dependent growth and migration of cancer cells
Publisher: Springer Science and Business Media LLC
Date: 29-10-2020
DOI: 10.1038/S41598-020-75941-6
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Rapid 3D Extrusion of Synthetic Tumor Microenvironments
Publisher: Wiley
Date: 18-08-2015
Cell‐Laden Gradient Microgel Suspensions for Spatial Control of Differentiation During Biofabrication
Publisher: Wiley
Date: 15-08-2022
Abstract: During tissue development, stem and progenitor cells form functional tissue with high cellular ersity and intricate micro‐ and macro‐architecture. Current approaches have attempted to replicate this process with materials cues or through spontaneous cell self‐organization. However, cell‐directed and materials‐directed organization are required simultaneously to achieve biomimetic structure and function. Here, it is shown how integrating live adipose derived stem cells with gradient microgel suspensions steers ergent differentiation outcomes. Microgel matrices composed of small particles are found to promote adipogenic differentiation, while larger particles fostered increased cell spreading and osteogenic differentiation. Tuning the matrix formulation demonstrates that early cell adhesion and spreading dictate differentiation outcome. Combining small and large microgels into gradients spatially directs proliferation and differentiation over time. After 21 days of culture, osteogenic conditions foster significant mineralization within the in idual microgels, thereby providing cell‐directed changes in composition and mechanics within the gradient porous scaffold. Freeform printing of high‐density cell suspensions is performed across these gradients to demonstrate the potential for hierarchical tissue biofabrication. Interstitial porosity influences cell expansion from the print and microgel size guides spatial differentiation, thereby providing scope to fabricate tissue gradients at multiple scales through integrated and printed cell populations.
Si-C linked oligo(ethylene glycol) layers in silicon-based photonic crystals: Optimization for implantable optical materials
Publisher: Elsevier BV
Date: 07-2007
DOI: 10.1016/J.BIOMATERIALS.2007.03.014
Abstract: Porous silicon has shown potential for various applications in biology and medicine, which require that the material (1) remain stable for the length of the intended application and (2) resist non-specific adsorption of proteins. Here we explore the efficacy of short oligo(ethylene glycol) moieties incorporated into organic layers via two separate strategies in achieving these aims. In the first strategy the porous silicon structure was modified in a single step via hydrosilylation of alpha-oligo(ethylene glycol)-omega-alkenes containing three or six ethylene glycol units. The second strategy employs two steps: (1) hydrosilylation of succinimidyl-10-undecenoate and (2) coupling of an amino hexa(ethylene glycol) species. The porous silicon photonic crystals modified by the two-step strategy displayed greater stability relative to the single step procedure when exposed to conditions of physiological temperature and pH. Both strategies produced layers that resist non-specific adsorption of proteins as determined with fluorescently labelled bovine serum albumin. The antifouling behaviour and greater stability to physiological conditions provided by this chemistry enhances the suitability of porous silicon for biomaterials applications.
Directing Stem Cell Fate by Controlling the Affinity and Density of Ligand–Receptor Interactions at the Biomaterials Interface
Publisher: Wiley
Date: 13-04-2012
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