Ferenc Horkay National Institutes of Health
Noshir Langrana Rutgers University
J. David Londono Dupont de Nemours and Co.
Wilhelm Oppermann Clausthal University of Technology
Richard G. Weiss Georgetown University
LL1: Nanoparticles and Gels
Monday PM, November 28, 2011
Room 101 (Hynes)
9:30 AM - **LL1.1
Multi-Component, Self-Assembled, Soft Materials.
Uday Maitra 1 Show Abstract
1 Department of Organic Chemistry, Indian Institute of Science, Bangalore, Karnataka, India
Uday MaitraDepartment of Organic ChemistryIndian Institute of ScienceBangalore 560 email@example.comIn recent years functional molecular gels have attracted considerable interest owing to their potential applications in various fields. Our group has been working on the aggregation of a variety of bile acid derivatives which form self-assembled fibrillar networks (SAFINs), eventually leading to the immobilization of solvent molecules around them. In this presentation, our efforts to organize multiple components on the SAFINs to generate luminescent materials with potential applications will be discussed.Recent References:1.“A self-assembled, luminescent europium cholate hydrogel: a novel approach towards lanthanide sensitization”, S. Bhowmik, S. Banerjee and U. Maitra, Chem. Commun, 2010, 46, 8642 (DOI: 10.1039/c0cc02939d).2.“Molecular Gels ‘in action’”, S. Banerjee, R.K. Das, U. Maitra, J. Mater. Chem. 2009, 19, 6649-6687.3."Nanoparticle-Gel Hybrid Material Designed with Bile Acid Analogues", Shreedhar Bhat and Uday Maitra, Chem. Mater. 2006, 18, 4224-4226.
10:00 AM - **LL1.2
Molecular Origin of Nonlinear Elasticity in Model Physically Associating Triblock Copolymer Gels.
Kendra Erk 1 , Kenneth Shull 2 Show Abstract
1 Polymers Division, National Institute of Standards and Technology, Gaithersburg, Maryland, United States, 2 Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois, United States
Nonlinear elasticity observed in shear rheometry experiments is coupled with molecular constitutive models and scaling laws to establish the relationships between the observed macroscale mechanical properties of a model physically associating gel with its underlying microstructural evolution during shear. Compared to previous studies of nonlinearity in soft materials, the work performed here benefits from studying polymer gels with well-defined molecular structures and a wide range of accessible relaxation times.The model gel is composed of acrylic triblock copolymer dissolved in a midblock-selective solvent. At elevated temperatures, the copolymer is fully dissolved and the solution behaves as a viscoelastic liquid with near Maxwellian relaxation. As the solution is cooled, the copolymer self-assembles into a three-dimensional transient network composed of spherical endblock aggregates interconnected by flexible midblock bridges. The relaxation time increases dramatically as temperature is reduced, such that at room temperature the system behaves as a viscoelastic gel. The temperature-dependent structure and resulting range of viscous-to-elastic behavior allow for these gels to be deformed at reduced rates (product of applied shear rate and the gel’s relaxation time) that span almost four orders of magnitude.During shear at a constant rate, strain-stiffening behavior is observed at small strains and related to the finite extensibility of the midblock bridges in the gel via a constitutive model based on an exponential strain energy function. Interestingly, the same model is also effective for describing the stiffening of various biopolymer networks. As deformation progresses, stiffening is followed by rapid, fracture-like softening in the stress response which is believed to result from the shear-induced formation of highly localized regions of deformation in the gel. This behavior is accurately captured by a constitutive model that incorporates the strain energy and relaxation of individual bridges in the gel. Flow curves predicted from the model are non-monotonic, consistent with the onset of flow instabilities at high shear rates. At large strains, plateaus in the stress response are observed and compared with results from traditional sliding friction experiments. Scaling law arguments from this large-strain regime suggest that deformation in the gel is confined to a localized shear zone with thickness comparable to the mesh size of the gel. The overall nonlinear stress response – stiffening, softening, and stress plateau – also displays an interesting rate dependence which may be evidence of a potential failure-mode transition in the deformed gel.The well-defined network structure of these triblock copolymer gels coupled with their tunable range of relaxation times allow for these gels to be useful model systems for future studies of flow instabilities in physically associating soft materials.
11:00 AM - LL1.3
Application of the Regular Solution Model to Interpret the Gelation Behavior of Low Molecular Mass Organogelators in Organic Solvents.
Kevin Cavicchi 1 , Li Feng 1 Show Abstract
1 , The University of Akron, Akron, Ohio, United States
Physical gels are complex soft materials that are composed primarily of a liquid, but display solid-like viscoelastic properties due to the presence of a gelator which forms a three dimensional network. An interesting class of gelators for organic fluids are low molecular mass organogelators (LMOGs). A variety of chemically different LMOGs have been discovered that self-assemble into three-dimensional fibrillar structures. Their ubiquity has led to their application in a number of fields including cosmetics, pharmaceuticals, foodstuffs, oil recovery, renewable energy, and materials templating. A fundamental question that remains in this field is what makes a good organogelator? While there has been significant investigation into the molecular organization of LMOGs, there has been comparatively less focus on their thermodynamic properties, such as the role of solvent-LMOG interactions. This talk will focus on a series of tripodal trisamide LMOGs with an identical core and range of alkyl substituents on the amide groups. When tested in a range of solvents clear differences were seen between the properties of the same LMOG in different solvents and different LMOGs in common solvents. This behavior was interpreted in terms of the regular solution model, which is commonly used to study non-ideal solutions. It was found that two important parameters influencing gelation are the solubility of the LMOG, which can be estimated by a solubility parameter, and its bulk melting temperature.
11:15 AM - LL1.4
Oxygen-Generating Gel Systems Induced by Visible Light and Application to Artificial Photosynthesis.
Kosuke Okeyoshi 1 2 , Ryo Yoshida 2 Show Abstract
1 , RIKEN Advanced Science Institute, Saitama Japan, 2 , The University of Tokyo, Tokyo Japan
Toward complete artificial photosynthesis systems to generate hydrogen and oxygen using visible light and water, oxygen-generating gel systems are designed and fabricated using the electrostatic interactions of ionic functional groups and steric effects of a polymer network. By using a graft polymer chain with Ru(bpy)32+ units as sensitizers to closely arrange RuO2 nanoparticles as catalyst, the functional groups transmit multiple electrons cooperatively to generate oxygen. In this study, a novel strategy is shown to design a hierarchical network structure using colloidal nanoparticles and macromonomers.Firstly, the gel network stabilized the RuO2 NPs, which worked as the catalysts for O2 generation (the GR system). Second, we prepared macromonomer having sensitizer on a side chain; poly(NIPAAm-co-Ru(bpy)3). SDS-RuO2 NPs could be stabilized by poly(NIPAAm-co-Ru(bpy)3) as a result of steric effects. In addition, the electrostatic interaction on multi-points between the SDS-RuO2 NPs and poly(NIPAAm-co-Ru(bpy)3) allowed the multi-electron transmission to generate oxygen smoothly. As a result of the steady dispersion of RuO2 NPs and the close arrangement of RuO2 NPs and Ru(bpy)32+ by the polymer chain, the GRR system with the immobilized catalyst and copolymerized sensitizer generated O2 gas. In future, by arranging the two kinds of gel systems; the O2-generating gel system and the H2 generating gel system, both light induced, it would be possible to create gel systems that perform complete artificial photosynthesis to generate both hydrogen and oxygen when visible light and water are supplied. They are necessary for fuel cells and the gel systems are useful as a solar energy converting systems or ‘artificial chloroplasts’.
11:30 AM - LL1.5
Micron-Scale Measurement of the Complex Modulus of Gel by Dynamic Instrumented Indentation.
Jennifer Hay 1 Show Abstract
1 Nanotechnology Measurements Operation, Agilent Technologies, Knoxville, Tennessee, United States
Dynamic instrumented indentation logically presents itself as a promising technique for the mechanical characterization of gels, because no special sample preparation is required, and testing can be done in fluid. Further, measurements are naturally localized, so there is good reason to hope that instrumented indentation might be used to map out spatial variations in properties. However, quantitative mechanical characterization of gels by instrumented indentation has proven challenging due to the fact that the magnitude of the measured response can easily be on the order of experimental uncertainty. Thus, in this work, comprehensive uncertainty analysis guides experimental design in order to achieve meaningful measurements on several common gels.
11:45 AM - LL1.6
The Surface Frictional and Mechanical Behaviors of Silicone Hydrogel-Based Contact Lens Materials.
Bo Zhou 1 , Nicholas Randall 1 , Samuel Marclay 1 , Lei Li 2 Show Abstract
1 , CSM Instruments Inc, Needham, Massachusetts, United States, 2 , University of Pittsburgh, Pittsburgh, Pennsylvania, United States
In recent years, the study of the surface properties of compliant materials (especially synthetic and biological hydrogels) has emerged as an urgent need for both industrial and academic fields. Silcone-based contact lens materials are a practical application of hydrogels used in daily life, on which the investigation of surface frictional and mechanical behaviors could contribute to the improvement of their clinical performance. However, to date, only a handful of researches have been conducted to understand the driven mechanisms of such behaviors. In this study, the tribological and mechanical properties of senofilcon-A contact lenses were systematically studied through nanotribology and nanoindentation methods in both liquid and dehydrated conditions. In the tribological study, a stainless steel counterpart was employed to wear the lens surface with various load and velocity conditions. It was found that the friction force is proportional to normal load as described by Amonton’s law and this unexpected behavior can be attributed to the fact that viscous flow contributes little to the overall friction and that solid-solid contact dominates the friction of silicon hydrogel. It was also found that the coefficient of friction increases with the velocity and the quantitative relationship between them can be explained reasonably well with a previously proposed “repulsion-adsorption” model. Furthermore, the stiffness of the hydrogel lens was measured by nanoindentation with direct compensation for thermal fluctuation and surface adhesive force. It was interesting to observe the dramatic change of gel stiffness during the dehydration process. The transition seemed to follow a non-linear trend with a certain time threshold of abrupt increase of stiffening rate. The dehydration also had a great influence on the material time dependent properties, such as creep degree. The impacts of material chemistry, water content, test media, applied load and the sliding velocity on these mechanisms were also discussed.
LL2: Design of Functional Polymer Gels
Monday PM, November 28, 2011
Room 101 (Hynes)
2:30 PM - **LL2.1
Gels for the Conservation of Cultural Heritage.
Piero Baglioni 1 , Massimo Bonini 1 , Emiliano Carretti 1 , Emiliano Fratini 1 , Rodorico Giorgi 1 Show Abstract
1 Department of Chemistry, University of Florence, Florence Italy
Works of art and artifacts that constitute our cultural heritage are subject to deterioration. Surfaces that interact with the environment are the most prone to aging and decay; accordingly, soiling is a prime factor in the degradation of surfaces and the attendant disfigurement of the work of art. Coatings, that were originally intended to protect or contribute aesthetically to a work of art, should be removed if they begin to have a destructive impact on its appearance or surface stability. This talk addresses the removal of organic coating from pictorial surfaces by using new colloidal systems:(1) Microemulsions and micellar solutions optimized for the removal of acrylic and vinyl polymers.(2) Responsive gels (nanomagnetic gels) with embedded microemulsions or micellar solutions. (3) Novel formulations of poly(vinyl alcohol)-borate gels, which accept a range of organic cosolvents.With illustrative examples, I will report on the properties and the applications of these systems in recent restoration workshops.
3:00 PM - **LL2.2
Structure and Kinetics of Gelation in Cellulose Derivatives.
Patrick Fairclough 1 , Anthony Ryan 1 , Oscar Kelly 1 , Hau Yu 1 Show Abstract
1 The Department of Chemistry, The University of Sheffield, Sheffield United Kingdom
Cellulose ethers (CE’s) are water soluble polymers derived from cellulose, which play an important role in many industry applications, such as food, pharmaceuticals, construction products, cosmetics, and so on. The two main commercial types of commercial cellulose ethers products have been investigated; methyl cellulose (MC) and hydroxypropyl methylcellulose (HPMC). Aqueous solutions of MC and HPMC systems form gels on heating returning to a liquid state on cooling. The gel growth mechanism in aqueous solutions of CE has been the subject of majordebate for many years. The mechanism is commonly believed to be a hydrophobic association that undergoes self assembly in aqueous solution upon heating, Optical micrographs revels that the gelation is due to the phase separation by spinodal decomposition.The textures are consistent with polymer rich and polymer poor region. Fast Fourier Transform image processing shows a broad weak ring and the dominant size is about 5µm.This domain spacing length is dependent on the concentration, the heating rate and the chemical substitution bias. The confocal fluorescence micrographs indicate that the syneresed-water pores develop in the HPMC gel. By judicious use of salts this same structure can be induced in MC systems. The rheology indicates that the gel formation evolves over time, however, the thermodynamic equilibrium condition cannot be met in the system, due to the timescales involved. The gelation can happen at temperatures 10 to 20°C lower than the conventionally quoted gel point, which is usually measured in a constant heating rate. This would suggest that gel structure is pinned by phase separation.
4:00 PM - **LL2.3
Enzyme-Instructed Formation of Molecular Nanofibers/Hydrogels for Biomedicine.
Bing Xu 1 Show Abstract
1 Chemistry, Brandeis University, Waltham, Massachusetts, United States
Like certain proteins that form fibrillary nanostructures (e.g., actin filament, microtubules, or paired helical filaments), small molecules can self-assemble in water to afford supramolecular nanofibers and result in hydrogels. While it is known that the intracellular filaments of the proteins intricately associate with normal cellular functions (e.g., cell movements) or illnesses (e.g., Alzheimer disease), the generation and destiny of the supramolecular nanofibers inside cells remain unexplored. We report a range of small molecules that undergo enzyme catalyzed transformation to form molecular nanofibers/hydrogels and discuss the use of enzyme to trigger self-assembly for generating molecular nanofibers and hydrogels after the designed substrates diffuse passively into cells. In addition, we show the potential applications of this enzymatic hydrogelation in biomedicine.
4:30 PM - LL2.4
Engineering Better Biomaterials to Reverse Type 1 Diabetes.
Kaitlin Bratlie 1 2 , Arturo Vegas 1 2 , Thema Vietti 1 , Alan Chiu 1 , Nimit Dholakia 1 , Robert Langer 2 3 1 , Daniel Anderson 2 3 1 Show Abstract
1 Koch Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States, 2 Department of Chemical Engineering, Massachusetts Insitute of Technology, Cambridge, Massachusetts, United States, 3 Division of Health & Sciences Technology, Massachusetts Insitute of Technology, Cambridge, Massachusetts, United States
According to the American Diabetes Association, diabetes affects over 20.8 million people in the United States or about 7% of the population. Type I diabetes is an autoimmune disease in which the insulin producing β-cells are destroyed by the immune system. Current treatments involve daily injection of insulin from recombinant human or animal sources. Controlling diabetes through insulin injections has proven difficult since regulation of insulin secreted by the β-cells of the pancreatic islets in response to blood glucose is a highly dynamic process. To circumvent this problem, we are particularly interested in developing materials for reducing host-responses for polymer encapsulated insulin producing β-cells, which has potential as a type I diabetes therapeutic. Encapsulating β-cells in polymers to evade host-responses was first proposed by Lim & Sun using alginate, a natural polymer derived from seaweed. Elliott et al. found that alginate encapsulated porcine islets remained viable 9.5 years after transplantation. However, they were encapsulated in fibrous tissue, resulting in poor diffusion of insulin into the patient’s blood stream. Based on these findings, our approach has been to develop a library of modified alginates for encapsulating β-cells that are more biocompatible than existing alginate. In assessing biocompatibility, our goal is to develop in vivo fluorescence imaging for assessing the host-response to libraries of implanted biomaterials to determine which chemical functionalities mitigate the foreign body response. We have developed a method for imaging the foreign body response through cathepsin activity imaging. Through this imaging platform, we are able to assess early time-point responses to implanted materials. We have examined a 1000 member library based on alginate for encapsulating β-cells. Histological analysis of these implanted materials complements early time point imaging in assessing host responses.Novel alginates identified as biocompatible through in vivo imaging and histology were used to encapsulate β-cells isolated from rats and were implanted into diabetic mice. Several polymers were found to be as efficacious as unmodified alginate in stabilizing blood glucose levels for periods longer than one month. Future plans in this work include developing a more apt mouse model to differentiate between unmodified and modified alginates.1.Lim, F.; Sun, A. M., Microencapsulated islets as bioartificial endocrine pancreas. Science 1980, 210, 908-910.2.Elliott, R. B.; Escobar, L.; Tan, P. L. J.; Muzina, M.; Zwain, S.; Buchanan, C., Live encapsulated porcine islets from a type 1 diabetic patient 9.5 yr after xenotransplantation. Xenotransplantation 2007, 14 (2), 157-161.
4:45 PM - LL2.5
A Synthetically Designed Gel for Controlled Release of Insulin.
Akira Matsumoto 1 , Takehiko Ishii 2 , Kazunori Kataoka 2 , Yuji Miyahara 1 Show Abstract
1 Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo Japan, 2 Department of Materials Science and Engineering, The University of Tokyo, Tokyo Japan
Diabetes is not an infectious disease but its increasingly rapid and worldwide prevalence has been recognized as "pandemic". Despite the necessity for continuous and accurate glycemic control in the management of insulin dependent diabetes mellitus (IDDM), the current palliative treatment relies almost solely on the patient-self injection of insulin, which not only impinges on quality of life of the patients but also fails to precisely control dose of insulin where the overdose must be strictly avoided otherwise causing serious hypoglycemia. Development of self-regulated insulin delivery systems is a long-standing challenge of materials science, for which exploitations of glucose oxidase and sugar-binding lectin are two prevalent rationales to install the function of glucose-sensitivity. These protein-based components, however, intolerant of long-term use and storage with their denaturing and cytotoxic natures, are hardly suitable for any implantable applications thus have not yet been in clinical usage to date. Here we describe a thoroughly synthetic and remarkably simple alternative. A polymer gel bearing phenylboronic acid (PBA) derivative was chemically optimized as to elicit abrupt and glucose-dependent transition in the state of hydration under physiological aqueous condition.1-5 During this transition, development of a thinly surface-dehydrated layer or "skin layer" was identified as a mode that is able to discretely switch the release of gel-loaded insulin, providing an ability to synchronize the dosage with the surrounding glucose-fluctuation in the range between normo- and hyperglycemia.6 This synthetic alternative may offer a new material basis for the self-regulated insulin delivery systems to treat diabetes with long-term stability and safety.
5:00 PM - LL2.6
Designing Biological Systems.
Pamela Silver 1 Show Abstract
1 , Harvard Medical School, Boston, Massachusetts, United States
Biology presents us with an array of design principles. From studies of both simple and more complex systems, we understand some of the fundamentals of how Nature works. We are interested in using the foundations of biology to engineer cells in a logical and predictable way to perform certain functions. By necessity, the predictable engineering of biology requires knowledge of quantitative behavior of individual cells and communities and the ability to construct reliable models. By building and analyzing synthetic systems, we learn more about the fundamentals of biological design as well as engineer useful living devices with myriad applications. For example, we are interested in building cells that can perform specific tasks, such as counting mitotic divisions and remembering past events thus acting as a biological computer. Moreover, we design cells with predictable biological properties that serve as cell-based sensors, factories for generating useful commodities and improved centers for carbon fixation. In doing so, we have made new findings about how cells interact with and impact on their environment.
5:15 PM - LL2.7
Supramolecular Nanofibers and Hydrogels of Nucleopeptides Resistant to Enzyme Digestion.
Xinming Li 1 , Yi Kuang 1 , Hsin-Chieh Lin 1 , Yuan Gao 1 , Junfeng Shi 1 , Bing Xu 1 Show Abstract
1 Chemistry, Brandeis University, Waltham, Massachusetts, United States
We report that the simple conjugation of nucleobases with small peptides generates a novel kind of nucleopeptides as supramolecular hydrogelators. As a class of molecules that contain both nucleobases and amino acids, nucleopeptides bear considerable biological and biomedical importance from antibiotics (willardiine-containing nucleopeptides and peptidyl nucleosides) to DNA analogs (peptide nucleic acids). Such biological significances render nucleopeptides as attractive targets for heterocyclic chemistry and useful molecules for studying biology. However, there is little work to use nucleopeptides for developing novel class of materials. In this study, we demonstrate the generation of a new type of hydrogelators based on the conjugates of nucleobases and short peptides that self-assemble in water to afford supramolecular hydrogels upon a pH- or enzymatic trigger. Besides that these hydrogelators barely inhibit the growth of mammalian cells, the inclusion of nucleobases in the hydrogelators significantly enhances their resistance to enzyme digestion, thus promising them to serve as new biomaterials for applications that require long-term biostability. This work, as the first example of nucleopeptides as hydrogelators made by an enzymatic reaction, provides a facile way to explore the potential applications of nucleopeptides as biomaterials, which may lead to a new and general platform to examine specific biological functions (e.g., binding to DNA and RNA) of a dynamic supramolecular system that is able to interact with both proteins and nucleic acids.
5:30 PM - LL2.8
Engineering Bioadhesive Hydrogels for Aneurysm Occlusion.
Marjan Rafat 1 , Lisa Rotenstein 1 , Jin-Oh You 1 , Debra Auguste 1 Show Abstract
1 Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States
Aneurysms pose a major health risk; 30,000 aneurysms rupture each year in the United States, causing stroke, permanent nerve damage, or subarachnoid hemorrhage. The current endovascular embolization method using platinum coils cannot treat wide-necked, large, or giant aneurysms. To create a new treatment paradigm, we synthesized photopolymerizable polyvinyl alcohol (PVA) gels to fabricate a space-filling material with engineered bioadhesion to inflamed endothelial cells. PVA was chosen for its low adhesiveness, non-degradability, and chemical tunability. PVA was modified to include methacrylate and amine side groups for photopolymerization and bioconjugation, respectively. We functionalized PVA surfaces with varying ratios of antibodies against cell adhesion molecules (CAMs) highly expressed on inflamed human umbilical vein endothelial cells (HUVECs). We validated gene expression profiles of endothelial leukocyte adhesion molecule-1 (ELAM) and vascular cell adhesion molecule-1 (VCAM) on HUVECs treated with interleukin-1α (IL-1α) to simulate an inflammatory environment. PVA gels were either modified with anti-ELAM only, anti-VCAM only, or a 1:1 ratio of anti-ELAM to anti-VCAM. HUVECs were stimulated with IL-1α before seeding onto the gels, and attachment was quantified after 2 and 24 hr. Cell adhesion was assessed by calculating the ratio of average cell number retained on gels centrifuged over those retained without centrifugation. Preliminary results showed strong and reversible cell attachment to PVA gels conjugated with either anti-ELAM or anti-VCAM. Though anti-ELAM and anti-VCAM facilitated strong adhesion at early times, this adhesion was reversed as a function of time. Synergistic binding of both anti-ELAM and anti-VCAM showed stable adhesion at 24 hr post-seeding. Endothelial cells were retained on 1:1 anti-ELAM:anti-VCAM presenting surfaces at a centrifugal force of 300xg; adherence decreased steadily with increased centrifugation speeds. An in vitro microfluidic aneurysm was designed to evaluate in situ polymerization and adhesion at physiological shear stresses of up to 15 dynes/cm2. Our findings suggest that cytokine-activated CAM expression may be used to engineer bioadhesive gels for the specific and effective adhesion of inflamed endothelial cells. Such materials have potential for use as an embolic agent for cerebral aneurysms as they may conform to any aneurysm geometry and maintain adhesion to prevent dislodging and vessel rupture.
5:45 PM - LL2.9
Structure and Assembly of DNA Nanoparticles.
Preethi Chandran 1 , Emilios Dimitriadis 1 , Ferenc Horkay 1 Show Abstract
1 , National Institutes of Health, Bethesda, Maryland, United States
DNA is an anionic polyelectrolyte, which occupies a large volume in salt free solution due to the coulomb repulsion between the charged groups. In the presence of polymer cations, DNA condenses into nanoparticles. DNA nanoparticles have generated a lot interest as a preferred vehicle for delivering therapeutic DNA in gene therapy. The efficiency of gene delivery is determined by stability and compactness of the particles. However not much is known about the organization of DNA within the particles. The large polymer cations condense DNA rapidly, with no distinct intermediate stages that give insight into the arrangement of DNA within the nanoparticle. In our work, we modulate the DNA length to slow down nanoparticle formation; and, by imaging with Atomic Force Microscopy (AFM), reconstruct the stages in the particle assembly. The results show that DNA within the nanoparticle is arranged as an inter-weaving network of uniform fiber condensates. The fiber condensates form from DNA condensing along its length, and appear to be the unit of DNA organization within the particle. We discuss how the condensation pathway is affected by the ion valence of the polymer cation. The mechanical properties of the nanoparticles are explored by nanoindentation using AFM. The nanoindentation measurements give insight into the internal organization of the particles and, by extension, the interactions governing nanoparticle formation. The fiber-condensate network is found to be loose and highly deformable, having as much as 95% water content.
LL3: Poster Session I
Tuesday AM, November 29, 2011
Exhibition Hall C (Hynes)
9:00 PM - LL3.1
Esterase-Instructed Formation of Molecular Hydrogel and Beta-Galactosidase-Instructed Intracellular Hydrogelation.
Fan Zhao 1 2 , Christopher Weitzel 3 , Susan Lovett 3 , Bing Xu 1 Show Abstract
1 Department of Chemistry, Brandeis University, Waltham, Massachusetts, United States, 2 Quantitative Biology Program, Brandeis University, Waltham, Massachusetts, United States, 3 Department of Biology, Brandeis University, Waltham, Massachusetts, United States
Supramolecular hydrogels made from small organic molecules usually possess inherently excellent biocompatibility and biodegradability, and they are considered as a possible alternative to polymeric hydrogels. To fabricate a molecular hydrogel, a commonly used method is to dissolve hydrogelators first and obtain a supersaturated solution by changing the temperature, pH, or ionic strength, resulting in molecular self-assembly and hydrogelation. This method, however, is not always working for certain hydrogelators with exceedingly low solubility and for hydrogelation in vivo. Here we choose two enzymes, carboxylic esterase and beta-galactosidase (β-gal), as the new triggers to explore its capability to construct molecular hydrogels and the potential biomedical applications. In the first part, we use carboxylic esterase to make a hydrogel of a molecule with exceedingly low solubility. The controlled hydrolysis of a carboxylic ester bond by carboxylic esterase acts as a trigger to initiate self-assembly in water and to form supramolecular hydrogels, even if the molecule itself is unable to form hydrogels by changing the pH or temperature. This method produces a supramolecular hydrogel that is stable over a wide pH range and insensitive to ionic strength. Based on the same concept of enzymatic hydrogelation, we demonstrate the first example of using β-gal to provide another pathway to intracellular hydrogelation. As an essential glycosidase, β-gal hydrolyzes a β-D-galactopyranoside and the aglycone self-assembles into supramolecular nanofibers and gels water. In addition, the precursor shows little inhibition towards E. coli, with and without active β-gal, suggesting that it is cell compatible. Given the prevalence of the enzymes in living organisms, this work contributes to the generation of self-assembled nanostructures via the action of enzymes.
9:00 PM - LL3.10
Investigating Thermoreversible Polyelectrolyte-Surfactant Complex Organogelators.
Ashley Lloyd 1 , Kevin Cavicchi 2 , Yuqing Liu 2 , Gustavo Guzman 3 Show Abstract
1 , Franklin W. Olin College of Engineering, Needham, Massachusetts, United States, 2 Polymer Engineering, The University of Akron, Akron, Ohio, United States, 3 Chemical Engineering, Universidad Nacional de Colombia, Bogota Colombia
Organogelators are compounds that cause physical gelation when combined with a non-aqueous fluid. They have found application in many areas including viscosity modification of consumer products to organic photovoltaics and templated nanostructured materials. Polyelectrolyte-surfactant complexes (PE-SURFS) are a new class of organogelators that can be simply prepared by the neutralization of a polyelectrolyte with an oppositely charged surfactant. In this presentation the organogelation of low-polarity aromatic solvents with poly (N,N-dimethyl-n-octadecyl ammonium p-styrene sulfonate) (PSS-DMODA) is presented. Gelation occurs thermoreversibly by heating and cooling a mixture of the PE-SURF and solvent. Inversion testing and cavitation rheology have been used to measure macroscopic gel transition temperatures. Gel transition temperature was found to be dependent on concentration of the polymer, the molecular weight of the polymer, and the gelled solvent. Polarized optical microscopy was used to monitor the birefringence of the gels towards understanding the molecular structure of the gels. In addition, the stability of the gels was monitored over longer periods of time as a function of both composition and annealing temperature. In some instances macrophase separation is observed where the solvent is expelled from the initially homogeneous gel. Both the gelation transition and macrophase separation will be discussed in terms of the underlying thermodynamic phase behavior, which is key to controlling the bulk properties of the gels. Ultimately these materials have great potential as a new class of organogelators due to the number of different parameters (molecular weight, surfactant, backbone chemistry) that can be independently tuned to control the bulk gel properties.
9:00 PM - LL3.11
Solubility and Structural Analysis of Synthetic Designer Self-Assembling Protein RADA16-I.
Ashley Cormier 1 , Carolina Ruiz-Orta 1 , Rufina Alamo 1 , Anant Paravastu 1 Show Abstract
1 , FAMU-FSU College of Engineering, Department of Chemical and Biomedical Engineering, Tallahassee, Florida, United States
Designer self-assembling peptides (small proteins) such as RADA16-I (1-2) are being used as nanofiber scaffolds for supporting tissue regeneration. A specific application of this material in regenerative medicine includes neuron regeneration (1), while the most interesting properties of designer self-assembling peptides include the ability to spontaneously self-assemble into nanofiber networks in water and dynamically reassemble in response to environmental stimuli (e.g., mechanical stress). In an effort to prepare isotopically labeled RADA16-I nanofiber for structural measurements, we have found the peptide to be difficult to dissolve with apparent solubility decreasing with storage time. In order to improve peptide solubility and nanofiber yield, we hypothesized that the synthetic peptide was slowly forming an undesired insoluble ordered state. In order to test this hypothesis, we quantified peptide solubility using ultraviolet-visible spectroscopy (UV-Vis) and monitored changes to peptide backbone conformation and inter-molecular organization in the solid state using solid state nuclear magnetic resonance spectroscopy (ssNMR) and Fourier transform infrared spectroscopy (FTIR). We also probed inter-molecular organization using ssNMR and wide angle x-ray diffraction (WAXD). We observed a slow (hours to days) structural transition in the peptide backbone from α-helical to β-strand conformation with increased order in intermolecular packing. Structural change correlates to loss of peptide solubility. These results clearly indicate that protocols for peptide nanofiber preparation must consider the effects of structure and intermolecular packing on solubility. 1.Ellis-Behnke, R. G., Y. X. Liang, S. W. You, D. K. C. Tay, S. G. Zhang, K. F. So, and G. E. Schneider. 2006. Nano neuro knitting: Peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision. Proceedings of the National Academy of Sciences of the United States of America 103:5054-5059.2.Yokoi, H., T. Kinoshita, and S. G. Zhang. 2005. Dynamic reassembly of peptide RADA16 nanofiber scaffold. Proceedings of the National Academy of Sciences of the United States of America 102:8414-8419.
9:00 PM - LL3.2
Rational Design, Self-Assembly, and Antibacterial Activity of Molecular Hydrogelators Derived from Kanamycin.
Ning Zhou 1 , Zhimo Yang 2 , Gaolin Liang 3 , Bing Xu 1 Show Abstract
1 Chemistry, Brandeis University, Waltham, Massachusetts, United States, 2 College of Life Sciences , Nakai University, Tianjin China, 3 Chemistry, University of Science and Technology of China, Hefei China
Kanamycin, an important class of antibitics that bind RNA to inhibit protein synthesis, has limited clinical usage because of antibacterial drug resistance. Here we report the self-assembly molecular hydrogelators derived from kanamycin A as a novel strategy to reduce antibacterial drug resistance related to Kanamycin. We find that the conjugation of Kanamycin A to naphthalene-phenylalanine-phenylalanine (Nap-FF) through the 6’-N amino group of Kanamycin results novel molecular hydrogelators, which preserve their antibacterial activities. This hydrogel not only preserves the advantage of multivalency, which enhanced the interaction between the kanamycin and 16S rRNA, but also contributed to reduce the bacterial resistance by preventing the acetylation of the 6’-N amino group, a common strategy for the resistant strain to inactivate the antibiotics. This approach indicates the potential use of kanamycin for developing antibacterial hydrogels that may lead to “self-delivery” of therapeutics.
9:00 PM - LL3.3
Enzymatic Formation of Fluorescent Supramolecular Hydrogels.
Yuan Gao 1 , Yi Kuang 1 , Junfeng Shi 1 , Hsin-Chieh Lin 1 , Bing Xu 1 Show Abstract
1 Chemistry, Brandeis University, Waltham, Massachusetts, United States
We report the synthesis and characterization of three fluorescent hydrogelators for tracking hydrogels in biological environment. Each hydrogelator contains a fluorophore by reacting the fluorogenic labeling reagent, 7-chloro-4-nitro-2,1,3-benzoxadiazole (NBD-Cl), 5-(dimethylamino)naphthalene-1-sulfonyl chloride (DNS-Cl), or 4-N,N-dimethylaminosulfonyl-7-fluoro-2,1,3-benzoxadiazole (DBD-F), with the side chain of the hydrogelator. To ensure the hydrogelation to occur in biological systems, we design and synthesize the precursors of the hydrogelators for enzymatic hydrogelation. Bearing the fluorophore and the enzyme switch (a tyrosine phosphate residue) that responds to alkaline phosphatase, the precursors undergo dephosphorylation catalyzed by the enzyme to generate the hydrogelators, which self-assemble in aqueous solution to form uniform nanofibers and result in fluorescent hydrogels. After hydrogelation, the NBD containing hydrogel becomes fluorescent from a quenched state in the aqueous solution; the DNS containing hydrogel fluoresces at a shorter wavelength than the solution does; and the DBD containing hydrogel shows an increased quantum yield. These indicative changes of the fluorophores during enzymatic hydrogelation not only confirm that the nanofibers of the fluorescent hydrogelators behave drastically different with the individual hydrogelators, but also provide useful candidates for studying molecular self-assembly in biological systems, such as cells.
9:00 PM - LL3.4
Structure/Property Relationships of Responsive LC Gels
Madeline Duning 1 , Anastasia Voevodin 1 , Michael McConney 1 , Lalgudi Natarajan 1 , Vincent Tondiglia 1 , Timothy White 1 , Timothy Bunning 1 Show Abstract
1 , Air Force Research Laboratory, Wpafb, Ohio, United States
Systematic investigations of a unique swelling/de-swelling/re-swelling transition involving ordered gels and ordered liquids crystal solvents (helical) are presented here. Functional monomers are templated and subsequently polymerized in an ordered LC fluid. The cell architecture is designed in such a way as to spatially control the placement of gel across the thickness of the cell which enables spatial anisotropic phase transitions to occur. This anisotropy in macromolecular architecture enables large scale changes in the optical properties (due to the chiral nature of the template fluid) of the as-formed gel due to localized responses of the gel near phase transition temperatures. Films which exhibit reflection across the visible and NIR spectral regions can be formed with a variety of reflection notch contrasts and bandwidths. This poster explores several variables as it relates to the dynamic changes in the optical properties in the continued study of these unique systems. The kinetics of the coloration changes are studied by examining the rate of heating the as formed swollen gel and changes in the complex optical properties are related to the underlying changes in helical macromolecular architecture. Differences in the thru-thickness spatial anisotropy (the extent of gel thickness) are also correlated to the magnitude of the optical changes observed.
9:00 PM - LL3.5
Criteria for Chemo-Mechanical Oscillations in Photosensitive, Self-Oscillating Polymer Gels.
Pratyush Dayal 1 , Olga Kuksenok 1 , Anna Balazs 1 Show Abstract
1 Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Via theory and simulations, we investigate the behavior of polymer gels undergoing Belousov-Zhabotinsky (BZ) reaction. Driven by the periodic reduction and oxidation of the ruthenium catalyst, which is grafted to the polymer network, the BZ gels undergo rhythmic mechanical oscillations and thereby exhibit chemo-mechanical transduction. However, the oscillations within the BZ gels can be completely suppressed with light of a certain wavelength. We exploit this property to direct the movement of these BZ gels along complex paths, guiding them to bend, reorient and turn. However, there is a particular range of parameters where this mechanism works. Through linear stability and normal form analyses, we isolate parameters for which the gel switches from oscillatory mode to stationary mode and vice versa. Specifically, we characterize the nature of Hopf bifurcations and identify regimes where this bifurcation is subcritical or supercritical. We also determine several other types of bifurcations within our system. These analyses allow us to establish necessary and sufficient conditions required to guide the movement of these active gels along complex paths.
9:00 PM - LL3.6
pH-Sensitive Injectable Hydrogel by Charge Driven Physical Crosslinking.
Seung Yong Lee 1 , Ju Eun Kim 1 , Jungkyu Kang 1 , Cheol-Hee Ahn 1 Show Abstract
1 Materials Science and Engineering, Seoul National University, Seoul Korea (the Republic of)
Injectable hydrogel systems using certain stimuli of physiological condition have many advantages in biomedical field. Regarding controlled delivery carriers, hydrogels are expected to be the most excellent carriers because water in their structure can prevent bioactive agents such as drugs, proteins and cells from degeneration. Also, to minimize surgical procedures, hydrogels which can be injected into body using syringe are required and a lot of researches have been reported. In this study, we designed pH-sensitive injectable hydrogel by blending oppositely charged polymers. Focusing on the delicate difference of pH between before and after injection, we decided to use sulfonamide type molecules because nitrogen of sulfonamide shows sharp deprotonation ability within narrow pH range. Also, varying conjugated alkyl groups of sulfonamides, their pKa values can be easily controlled. Considering the purpose of injection, we selected sulfadiazine with pKa value of 6.5. In other words, sulfadiazine exhibits negative charges at pH 7.4 though it is neutral at pH 6.0. However, sulfadiazine is not soluble in water when it has no charge so copolymerization with hydrophilic moiety is essential to the purpose of increasing water solubility. As a hydrophilic moiety, PEG (poly(ethylene glycol)) was selected and sulfadiazine methacryloylamide was polymerized from both two end groups of PEG via ATRP (atom transfer radical polymerization). Triblock copolymer was successfully synthesized as confirmed by GPC (gel permeable chromatography). After successful polymerization, PSDM (poly(sulfadiazine methacryloylamide) - PEG - PSDM triblock copolymer is soluble irrespective of pH. As a counterpart polymer, PAH (poly(allylamine hydrochloride)) was chosen. PAH has positive charge both at pH 7.4 and at pH 6.0. Triblock copolymer solution and PAH solution are prepared respectively and each solution was adjusted to pH 6.0. After mixing, the solution displays sol state and this might be because there is no interaction between two polymers. However, as the environment changes from pH 6.0 to pH 7.4, the solution turned into gel which is the state of no flow. Due to negative charges of triblock copolymer, charge driven physical crosslinking resulted from ionic interaction occurs and, finally, gel state is observed. Further, to the purpose of effective crosslinking, the blend ratio was controlled. This blend system hydrogel is expected to be applied to the delivery carrier of hydrophilic drugs, proteins and cells for sustained release.
9:00 PM - LL3.7
The Function and Differentiation of Myelinating Oligodenrocytes are Modulated by Their Mechanical Environment.
Anna Jagielska 1 , Adele Norman 2 , Graeme Whyte 3 , Robin Franklin 2 , Jochen Guck 3 , Krystyn Van Vliet 1 4 Show Abstract
1 Materials Science and Engineering, MIT, Cambridge, Massachusetts, United States, 2 Department of Veterinary Medicine and Cambridge Centre for Brain Repair, University of Cambridge, Cambridge United Kingdom, 3 Department of Physics, Cavendish Laboratory, University of Cambridge, Cambridge United Kingdom, 4 Biological Engineering, MIT, Cambridge, Massachusetts, United States
The myelination, process in which myelin sheaths are formed around axons, is fundamental for development and regeneration of central neural system (CNS). Critical to this process is the differentiation of oligodendrocyte precursor cells (OPCs), which is concurrent with gross morphological changes as the cells migrate to and wrap around axons. As studies have so far only considered the biochemical stimulation of that differentiation, it is entirely unknown whether physical stimuli may regulate or contribute to this process. Here we show that OPCs are mechano-sensitive and respond to stiffness of their surroundings. Adhesion, survival, proliferation, stiffness, migration, spreading, morphology, and ultimately differentiation of OPCs were correlated with the stiffness of polyacrylamide gels on which they are cultured. Within the physiological stiffness range of CNS tissue most of these properties showed response to gel stiffness. Interestingly, while the compliance of the cells decreased during differentiation, it was largely insensitive to gel stiffness. This dependence of OPCs differentiation on mechanical conditions of their environment might shed new light on the lack of remyelination after trauma or in neurodegenerative diseases such as multiple sclerosis.
9:00 PM - LL3.8
Depth Dependent Osmotic and Swelling Properties of Cartilage.
Candida Silva 1 , Iren Horkayne-Szakaly 1 , Preethi Chandran 1 , Emilios Dimitriadis 1 , Christopher Papanicolas 1 , Peter Basser 1 , Ferenc Horkay 1 Show Abstract
1 , NIH, Bethesda, Maryland, United States
The morphology of the major macromolecular components of the cartilage matrix (aggrecan, collagen, etc.) is investigated in near physiological condition using the Atomic Force Microscope (AFM). It is found that proteoglycan assemblies display remarkable insensitivity to changes in the salt concentration and ion valence in the surrounding environment. It is demonstrated that the behavior of aggrecan is qualitatively different from that of other biopolymers such as DNA, which collapse and form nanostructures in the presence of multivalent ions. The osmotic modulus is the quantity that governs the compressive resistance of cartilage to external loading. The osmotic modulus of bovine cartilage samples is determined by combining tissue micro-osmometry with measurements made by the AFM. It is found that the water retention is stronger in the upper and deep zones of cartilage, where the collagen fibers are ordered, than in the middle zone where they are randomly arranged. We have constructed the elastic and osmotic modulus maps for the different layers. The latter that is a combination of the elastic and swelling properties, exhibits much stronger spatial variation reflecting the highly heterogeneous character of the tissue.
9:00 PM - LL3.9
Bioresponsive Polymers Based on Modified Polysaccharides for Enzymatic Controlled Release.
Konstantin Schneider 1 , Andrea Hasmann 1 , Eva Wehrschuetz-Sigl 1 , Teresa Flock 1 , Ulrike Gewessler 1 , Doris Schiffer 2 , Georg Guebitz 1 2 Show Abstract
1 Institute of Environmental Biotechnology, ACIB GmbH, Graz, Styria, Austria, 2 Institute of Environmetal Biotechnology, Graz University of Technology, Graz, Styria, Austria
Bioresponsive polymers (BRP) are assembled to detect the presence of contaminating bacteria or fungi. Microorganisms release extracellular enzymes which can be used to effect a controlled release of different substances ranging from small (dyes) up to large and complex molecules (e.g. enzymes). Common systems of (bio) responsive polymers are designed to be sensible to pH or temperature changes in different environments [1; 2]. A more selective system is obtained with devices responding to trigger enzymes.In this study pectinases and cellulases produced by bacteria or fungi were investigated as trigger enzymes to hydrolyze natural polysaccharides e.g. polygalacturonic acid (PGA) or carboxymethylcellulose (CMC) and consequently release model molecules.Polysaccharide based polymers were assembled as hydrogels, containing up to 5% solid mass polysaccharide and 95% water but their stability is inadequately, e.g. the auto degradation of hydrogels. In order to design a stable hydrogel made of PGA or CMC, a cross-linking system was developed based on covalent integration of methacrylate substituents to the polysaccharide backbone via direct esterification . These methacrylate groups were polymerized by radical polymerization allowing various ratios of cross-linker to backbone for optimized stability without the loss of enzymatic sensitivity for optimizing stability effects against enzymatic sensitivity.To test the controlled release, alizarin as a model molecule was incorporated into the hydrogel matrix and tested against different activities of pectinases and cellulases. The release of alizarin was quantified via spectrophotometric measurements . In addition to enzyme triggered release, B. subtilis and Y. entercolitica, were used as model organism, which successfully triggered the release of alizarin.Aditionally, enzymes (laccase or lysozyme) were incorporated into the BRPs. Again, these enzymes were released from BRPs upon incubation with trigger enzymes or microorganisms. Subsequently, the released laccases were used to initiate a color reaction (enhancing the signal compared to loaded dyes only) while lysozyme was used to kill bacteria.  E.S. Sil et al, (2004) Prog. Polym. Sci, 29:1173-1222 L.S. Nair et al, (2007) Prog. Polym. Sci, 32:762-798 J. Fhilype et al, (2008) Int. J. Pharm, 355: 184-194 K.P. Schneider et al, (2011) Enzym Microb. Technol, 48: 312-318
Ferenc Horkay National Institutes of Health
Noshir Langrana Rutgers University
J. David Londono Dupont de Nemours and Co.
Wilhelm Oppermann Clausthal University of Technology
Richard G. Weiss Georgetown University
LL4: Bioactive Gels and Tissue Repair
Tuesday AM, November 29, 2011
Room 101 (Hynes)
9:30 AM - **LL4.1
Cell-Seeded Hydrogels for Cartilage Repair: Growing Spheroidal Matrix Gels in a Gel.
Alan Grodzinsky 1 Show Abstract
1 Biological, Mechanical and Electrical Engineering, MIT, Cambridge, Massachusetts, United States
Tissue engineered constructs for cartilage repair utilize hydrogel scaffolds seeded with chondrocytes, bone marrow stromal cells (BMSCs), or other cell types that can undergo chondrogenesis to generate a cartilage-like extracellular matrix (ECM) intended to function in place of diseased or injured tissue. Cell synthesis of pericellular and extracellular matrix de novo is known to depend on the microenvironment of the cells, including hydrogel scaffold stiffness, hydraulic permeability and molecular composition. In turn, the nano- and micro-scale poro- and viscoelastic properties of the newly synthesized ECM-gel depends on the composition and relative quantities of cell-secreted members of the proteoglycan, collagen, and non-collagenous protein superfamilies. We have studied cartilage-like neotissue synthesized by immature and adult bovine and equine BMSCs and chondrocytes within self-assembling peptide hydrogel scaffolds and, for comparison, within agarose hydrogels as a well accepted control. Both AFM-based nanoindentation and macroscopic biomechanical tests were used to quantify newly synthesized cell-associated matrix as well as macro-tissue construct properties over a wide of frequencies (dynamic behavior) and time scales (transient behavior). BMSC chondrogenesis within (KLDL)3 and (RADA)4 peptide hydrogels showed differential cell morphologies, proliferation, gene expression and matrix biosynthesis profiles in the presence of chondrogenic medium (containing TGF-b1 and dexamethasone). Both tissue-level biomechanical properties and the nano-molecular properties of newly synthesized aggrecan depended on cell type (i.e., BMSC vs chondrocyte) and animal age. Interestingly, peptide gel constructs seeded with adult equine BMSCs resulted in a cartilage neotissue having the highest dynamic stiffness compared to constructs using foal BMSCs and even foal chondrocytes. Correspondingly, aggrecan synthesized by adult equine BMSCs after 21 days of chondrogenic culture showed the highest molecular level stiffness and contained GAGs similar in length and sulfation pattern to newborn cartilage. These results have important implications for translation to animal studies aimed at optimization of scaffold and cell-source for cartilage repair.
10:00 AM - **LL4.2
Modified Alginate Hydrogels to Control Growth Factor Binding for Cartilage Tissue Engineering.
Lawrence Bonassar 1 Show Abstract
1 Biomedical Engineering, Cornell University, Ithaca, New York, United States
The storage and release of growth factors is an important but understudied function of the extracellular matrix of connective tissues. An excellent example of this is the control of insulin-like growth factor-I (IGF-I), a protein important in many diseases including diabetes, arthritis, and cancer. The activity of IGF-I is controlled in part via binding to IGF-binding proteins (IGFBPs). IGFBPs interact with IGF-I through a hydrophobic binding pocket on their N-terminus that enables them to bind IGF-I with high affinity (KD = 1-10 nM). Thus IGFBPs enables the ECM to act alternatively as a sink or source for IGF-I as needed. To date this high affinity binding and sink/source role of the ECM has not been exploited in the design of scaffold materials for tissue engineering. The entire binding domain of IGFBPs is too large to be incorporated into a material because the domains are large (~30 amino acids) and tertiary and quarternary structure are important for proper binding. As such, we hypothesized that short peptide sequences from the binding domain could enhance the IGF-I binding activity. We examined the effect of grafting peptide sequences from the IGF-I binding domain of IGFBP-5 that ranged from 3 to 13 amino acids to alginate, a biopolymer commonly used for 3D cell culture and therapeutic cell delivery. We examined the effect of grafting these peptides on the rate of release of IGF-I from alginate beads and on the biosynthetic activity of chondrocytes encapsulated in alginate beads. Peptides from IGFBP-5 were grafted to alginate using a G3 leader sequences at the N-terminus via carbodiimide chemistry. The final ligand denisities in alginate were varied from 0-41 micromolar, as confirmed by NMR analysis. The effect of binding peptide length and density was determined by measuring kinetics of IGF-I release from modified gels and by examining the biosynthesis rates of cells encapsulated in modified gels. The rate of IGF –I release was fastest from unmodified alginate and decreased as ligand length and density increased. Specifically, as ligand length increased from 3 to 13 peptides, the time constant for release of doubled. As ligand density was varied over 2 orders of magnitude for each peptide residue, the times constant for release increased monotonically with ligand density. Cell culture studies showed that peptide length altered biosynthetic activity as indicated by glycosaminoglycan (GAG) content. Ligand density increased proteoglycan accumulation for all peptide lengths. The maximal effect on biosynthesis was similar for all peptide lengths, but this stimulatory effect occurred at lower densities for larger peptides (110 nM for 13 peptides vs 2.1 uM for 3 peptides). These studies demonstrate the feasibility of using a biomimetic approach to control growth factor binding to tissue engineering scaffolds. This method has wide applicability to a variety of growth factors and therapeutic tissue targets.
11:00 AM - **LL4.3
Confocal-Rheology of Type-I Collagen Gels.
Daniel Blair 1 , Richard Arevalo 1 , Jeffery Urbach 1 Show Abstract
1 Physics, Georgetown Univeristy, Washington, District of Columbia, United States
Soft and biological materials often exhibit disordered and heterogeneous microstructure. In most cases, the transmission and distribution of stresses through these complex materials reflects their inherent heterogeneity. We have developed a set of techniques that provide the ability to apply to quantify the connection between microstructure and local stresses in the presence of a globally applied strain by combining confocal microscopy with rheology. We subject biopolymer matrices to uniform shear deformations while measuring the transmission of stress at the boundaries. I will describe our recent results on the size dependent nonlinear rheology of type I collagen networks. We utilize a modified version of traction force microscopy to help elucidate how the material microstructure determines the bulk material properties. I will present our preliminary results that suggest that the signatures of yielding in these materials follow a universal form.
11:30 AM - LL4.4
Theory of Fluid Lubrication of Hydrogels and Articular Cartilage during Compression under an Applied Load.
Jeffrey Sokoloff 1 Show Abstract
1 Physics Department, Northeastern University, Boston, Massachusetts, United States
The fluid lubrication model for articular cartilage put forward by Ateshian, in which a high percentage of the load is supported by fluid pressurization as the cartilage is compressed under load, is improved upon by proposing a model, based on contact mechanics, which takes into account the escape of fluid from the cartilage-cartilage interface. It predicts that for mean asperity height small compared to a length scale (which depends on the cartilage or hydrogel permeability, the fluid viscosity and the dimensions of the cartilage or hydrogel) over 90 percent of the load is supported by fluid pressurization.
11:45 AM - LL4.5
Mechanical Measurements of Hyaluronan-Rich Pericellular Coats.
Louis McLane 1 2 , Anthony Kramer 1 2 , Heike Bohem 3 , J. Curtis 1 2 Show Abstract
1 Physics, Georgia Tech, Atlanta, Georgia, United States, 2 Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, Georgia, United States, 3 New Materials and Biosystems, Max Planck Institute for Metals Reserach, Stuttgart Germany
The structure and mechanical attributes of the pericellular matrix on rat chondrocyte cells are characterized using a combination of optical tweezer force measurements, quantitative particle exclusion assays, and live cell fluorescent imaging of the matrix. The pericellular coat consists of a polysaccharide and protein rich polymer matrix that is grafted to the extracellular portion the plasma membrane. This hydrated polymer film often extends 1-10 microns, and yet is largely ignored because it is not easily visualized. Present on many mammalian cell types, the cell coat has been implicated in influencing several biophysical processes including filtration, acting as a growth factor reservoir, mechanoprotection, mechanosensing, and mediating cell proliferation and migration by influencing cell adhesion. Much work remains to be done to investigate these implications. Our studies focus on developing assays to interrogate the cell coat by combining experimental techniques with polymer physics models of surface-grafted polymers. Comparison of typical force curves produced by optical tweezer measurements with particle exclusion assays show that force can be detected slightly beyond the region of the exclusion area and far beyond the regions highlighted by fluorescent-labeling of hyaluronan, the gigantic linear polysaccharide and backbone molecule of many cell coats, including those of fibroblasts, chondrocytes, mesenchymal stem cells and smooth muscle cells. Force curves are reproducible over several sequential measurements on the same cell and between different cells. Comparison with theoretical predictions of the force on a sphere pressed into a polymer brush fit well with the force data. Further, the fitted data yields predictions of the polymer grafting density and brush thickness consistent with molecular dimensions and particle exclusion data. In order to estimate the local osmotic pressure, and hence estimate the local mesh size, the force versus distance curves have been used to extract a profile of the pressure throughout the cell coat.
12:00 PM - LL4.6
A Finite Element Approach for Design of Tissue Surrogate Polymer Systems.
Roza Mahmoodian 1 , Zeynep Kalcioglu 1 , Krystyn Van Vliet 1 2 Show Abstract
1 Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States, 2 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
There has been a growing need for biomimetic gels that can be implemented as tissue surrogates to serve as test media for examining effects of ballistics on soft tissues, as well as designing devices and protective garments to minimize blunt impact trauma on soldiers. These materials must exhibit optimized mechanical responses and energy dissipation characteristics under a wide range of loading conditions. The limited mechanical tunability of current materials highlights the importance of further investigations. Furthermore, lab measurements are inefficient and insufficient as a stand-alone technique. Such experimental approaches are time consuming and costly due to the numerous variables that characterize such polymer systems, e.g. molecular weight, composition, and macromolecular structure that all may confer unique mechanical performance suitable for the particular application.In the present work, we studied a variety of gel designs using finite element methods to provide guidance for design of tissue surrogate gels with optimal mechanical performance. As a benchmark and a means to validate our technique, we tested tissues obtained from porcine heart and liver in quasi-static and high strain rate impact loading regimes. Our results show promising prospects for macroscale to nanoscale design of viable soft-tissue surrogate materials.
12:15 PM - LL4.7
Matrix Modulus Affects Invasion Rate of Tumor Cells through Synthetic Hydrogels.
Esmaiel Jabbari 1 Show Abstract
1 Chemical Engineering, University of South Carolina, Columbia, South Carolina, United States
Introduction: Cell invasion is central to many biological events and pathological processes. Understanding cell-matrix forces responsible for invasion in synthetic matrices not only allows us to investigate the underlying mechanism of many pathological processes but also holds promise for designing improved engineered constructs for tissue regeneration. The objective of this work was to investigate the effect of matrix stiffness on invasion of tumor cells through a synthetic hydrogel with well-defined physical, mechanical, and biological properties.Experimental: A novel star acrylate-functionalized polyethylene glycol-co-lactide (SPELA) macromer was synthesized to produce hydrogels with well-defined water content, elastic modulus, degree of crosslinking and hydrophilicity. Acrylamide-terminated RGD cell adhesive peptide was synthesized in the solid phase on a Rink Amide resin. Hydrogel was formed by photo-polymerization of the macromere with or without RGD peptide. The hydrogels will be characterized with respect to elastic modulus, water content, contact angle, and degradation. Invasion experiments will be carried out in a transwell with the SPELA hydrogel as the invading matrix. Briefly, the SPELA gel was placed in the upper chamber of a 24-well Transwell. 4T1 breast tumor cells were seeded on the hydrogel and incubated for 12 h to allow invasion of cells in the hydrogel. After 12 h, the lower side of the membrane were fixed and counted with an inverted fluorescent microscope in randomly selected areas. The cell count was divided by surface area and time to obtain cell flux through the hydrogel.Results: The concentration of SPELA macromere ranged from 10-25% in water and that of RGD peptide was 1x10-4 to 1x10-2 M. The shear modulus of the hydrogel varied from 200 Pa to 25 kPa as the SPELA macromer concentration increased from 10 to 25%. Cell invasion was slightly increased as the RGD concentration was increased from 0 to 0.75% by weight of the macromer. However, RGD concentration >1% resulted in significant decrease in cell migration. As the matrix stiffness was increased from 0.15 to 0.4, 3, 5, 6, 14, and 25 kPa the invasion rate decreased from 18.0 to 5.5, 6, 5.7, 5.2, 1.5, and 1.0 cells/mm2 h, respectively. There was a drastic decrease in invasion rate for matrix stiffness greater than 10 kPa. Conclusion: Results demonstrate that matrix stiffness plays a major role in invasion of tumor cell through synthetic matrices with well-defined properties. Understanding factors affecting cell invasion can impact the design of engineered constructs for tissue regeneration with improved cell migration and invasion.
12:30 PM - LL4.8
Design of Injectable Superstiff Hydrogels for Stem Cell Mobilization.
Hyunjoon Kong 1 , Youyun Liang 1 2 , Yen Wah Tong 2 , Tor Jensen 1 , Edward Roy 1 Show Abstract
1 Chemcial & Biomolecular Eng., Univ. of IL-Urbana-Champaign, Urbana, Illinois, United States, 2 Chemical & Biomolecular Engineering, National University of Singapore, Singapore Singapore
Stem cell mobilization has emerged as a promising strategy to treat various chronic diseases and acute injuries. This therapy is commonly implemented by repeatedly administering granulocyte colony stimulating factor (GCSF). Recently, there have been efforts to encapsulate GCSF in injectable and biodegradable hydrogels, so as to sustain stem cell mobilization without repeating drug administrations. Hydrogels used for this therapy should be rigid to prevent uncontrolled drug release due to local tissue pressures, but degrade at a controlled rate to ensure the sustained drug release during the therapeutic window. However, conventional hydrogels are often plagued by limited drug release rates with increasing material stiffness. This study presents a new hydrogel with extremely high elastic modulus, similar to that of polystyrene, but with controllable drug release rates. The hydrogel was formed from Michael reaction between acrylate groups of poly(ethylene glycol) diacrylate (PEGDA) and amine groups of poly(ethylene imine) (PEI). The hyperbranched architecture of PEI contributed to increasing stiffness of the hydrogel while the amine groups led the gels to swell and release drugs at a controlled rate. Hydrogels were formed from varied compositions of PEGDA and PEI, and material properties such as elastic moduli, swelling rate, hydrogel water profile and release rates were extensively characterized. Finally, a single intramuscular injection of GCSF-encapsulating hydrogels into porcine models led to sustained mobilization of stem cells into circulation over four days and significantly enhanced CD34+ cell mobilization as compared to a control condition to deliver GCSF via daily bolus injection.ReferencesLiang Y. Jensen, T.W., Roy, E. J., Cha, C., DeVolder, R., J., Kohman, R.E., Zhang, B.Z., Textor, K.B., Rund, L.A., Schook, L.B., Tong, Y.W., & Kong, H.J. Biomaterials 32, 2004 (2011).
12:45 PM - LL4.9
In Situ Forming Hyaluronate Hydrogels by Host-Guest Chemistry Encapsulating Mesenchymal Stem Cells for Cancer Therapy.
Junseok Yeom 1 , Hyuntae Jung 2 3 , Sang Hoon Park 4 , Jung-A Yang 1 , Kimoon Kim 2 3 , Young Chul Sung 4 , Sei Kwang Hahn 1 3 Show Abstract
1 Department of Materials Science and Engineering, POSTECH, Pohang, Kyungbuk, Korea (the Republic of), 2 Department of Chemistry, POSTECH, Pohang, Kyungbuk, Korea (the Republic of), 3 School of Interdisciplinary Bioscience and Bioengineering, POSTECH, Pohang, Kyungbuk, Korea (the Republic of), 4 Department of Life Science, POSTECH, Pohang, Kyungbuk, Korea (the Republic of)
Hydrogels that mimic extracellular matrices have been used as platforms for 3D cell culture and tissue engineering. Here, we report novel biomimetic hydrogels formed from hyaluronate (HA) conjugated with the synthetic molecules of cucurbituril (CB) and polyamines (PAs). The strong and selective host-guest interaction between CB and PA drives self-assembly of the hydrogels in the presence of cells in vitro and even in vivo. Furthermore, functional “tag” moieties can be easily introduced into the hydrogels during or after gelation by anchoring various “tag”-attached CB to residual PA moieties in the hydrogel. As a model system for tissue engineering applications, mesenchymal stem cells (MSCs), which were genetically modified with recombinant adenovirus and cell permeable peptides to secrete IL-12 for the production of tumor necrosis factor-α, were encapsulated within the HA-CB/PA hydrogels. Then, the HA-CB/PA hydrogels were modularly modified with dexamethasone conjugated CB (DMT-CB). In vitro release tests exhibited the continuous release of IL-12 from the hydrogels for up to 2 weeks. Currently, in vivo applications of the HA-CB/PA/DMT-CB hydrogels encapsulating IL-12 releasing MSCs are under investigation for the treatment of cancer in C57BL/6 melanoma model mice. The clinically feasible in situ forming HA-CB/PA hydrogels by host-guest chemistry will be investigated further for various cell therapy and tissue engineering applications.
LL5: Physical Gels and Self-Assembly
Tuesday PM, November 29, 2011
Room 101 (Hynes)
2:30 PM - **LL5.1
Self-Assembly Model of Entanglement.
Jack Douglas 1 Show Abstract
1 , NIST, Gaithersburg, Maryland, United States
Polymer, fiber-like, and even sheet-like structures having sufficient conformational complexity to avoid liquid crystalline ordering often exhibit a complex rheological behavior termed ‘entanglement’. A model of this general phenomenon in polymer fluids is developed based on the idea that inter-chain correlations associated with packing and topological interactions between the chains leads to a transient local caging of the chains by surrounding chains so that groups of chains move collectively in the form of polydispdisperse amoeba-shaped clumps that form and disintegrate in dynamic equilibrium. In particular, entanglement is viewed as a form of entropically driven self-assembly and a generalization of the critical Onsager-Flory aspect ratio for liquid crystal ordering is introduced to estimate the entanglement molecular mass. Further, simple arguments are made to describe shear stress relaxation, the mass dependence of the shear viscosity and diffusion coefficient, the shear rate dependence of the shear viscosity and the normal stresses of polymer melts based on this idealized model of entanglement and predictions of the model are compared to experiment. Evidence for this type of dynamic clustering is provided from both simulation and experiment on simple disordered fiber models that clearly illustrate the nature of entanglement implied by the modeling. The entropic self-assembly model of entanglement implies that entangled polymer melts are dynamically heterogeneous, as in the case of glass-forming liquids, and numerous parallels between these complex fluids can then be expected.
3:00 PM - **LL5.2
Synthesis and Investigation of Chiral Supramolecular Self-Assemblies of Novel Amino Acid Based Pyrimidine Derivatives.
Santanu Bhattacharya 1 , Sougata Datta 1 Show Abstract
1 Organic Chemistry, Indian Institute of Science, Bangalore India
A family of supramolecular organogelators based on novel amino acid derivatives of 2, 4, 6-trichloro-pyrimidine-5-carbaldehyde has been synthesized. A β-sheet type of extensively hydrogen bonded aggregation mode of such compounds was elucidated from these molecules in organic solvents when investigated using various physical methods such as UV-visible, FT-IR, circular dichroism spectroscopy, electron microscopy, small-angle and wide-angle X-ray diffraction and rheology. Calculation of the molecular lengths from energy minimized conformations and comparison with the small-angle X-ray diffraction patterns reveal that this class of gelator molecules adopt interdigitated lamellar structures, thus confirming the existence of strong van der Waals interaction of hydrophobic alkyl chains in such aggregates. The solid phase behavior of this series of compounds has been investigated further using polarized optical microscopy (POM) and differential scanning calorimetry (DSC). The solid phase behavior of these molecules in POM and solid phase DSC experiment are totally dependent on the choice of their amino acid residues.
4:00 PM - **LL5.3
Gelling and Ungelling Blood via Self-Assembly.
Srinivasa Raghavan 1 , Matthew Dowling 1 Show Abstract
1 Chemical & Biomolecular Engineering, University of Maryland, College Park, Maryland, United States
When we suffer a wound, our body responds by initiating the clotting cascade at the wound site whereby a clot is formed to arrest the loss of blood. The clot is a self-assembled gel of the protein fibrin, and the blood cells are immobilized within this gel. Gelation of blood is thus critical to prevention of bleeding from serious wounds, e.g., in the case of soldiers on the battlefield. At the same time, if a gel (clot) travels through the body, it could lead to stroke – therefore, it is desirable to be able to reverse blood gelation. Here, we demonstrate the ability to both gel blood using a self-assembling biopolymer and reverse the gelling using a sugar-based supramolecule. The biopolymer is a hydrophobically modified (hm) derivative of the polysaccharide, chitosan. When hm-chitosan is contacted with heparinized human blood, it rapidly transforms the liquid into an elastic gel. In contrast, the native chitosan (without hydrophobes) does not gel blood. Gelation occurs because the hydrophobes on hm-chitosan insert into the membranes of blood cells and thereby connect the cells into a sample-spanning three-dimensional network. The above process can be readily reversed by the addition of a type of cyclodextrin, which is a supramolecule having an inner hydrophobic pocket. When the cyclodextrin is added, hydrophobes detach from blood cells and embed within the hydrophobic pocket of the cyclodextrin, thereby disrupting the cell network. We are currently evaluating hm-chitosan bandages as low-cost hemostatic dressings for use by trauma centers and the military. Preliminary tests with small and large animal injury models show the efficacy of hm-chitosan bandages at achieving rapid hemostasis. [Reference: Dowling et al., Biomaterials, 32, 3351 (2011).]
4:30 PM - LL5.4
Injectable Solid Peptide Hydrogels for Curcumin Delivery to Tumors.
Darrin Pochan 1 , Aysegul Altunbas 1 , Sigrid Rajasekaran 2 , Joon Seung 2 , Joel Schneider 3 Show Abstract
1 Materials Science and Engineering, University of Delaware, Newark, Delaware, United States, 2 Nemours Center for Childhood Cancer Research, AI duPont Hospital for Children , Wilmington, Delaware, United States, 3 Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States
Curcumin, a hydrophobic polyphenol, is an extract of turmeric root with antioxidant, anti-inflammatory and anti-tumorigenic properties. Its lack of water solubility and relatively low bioavailability set major limitations for its in vivo therapeutic use. A self-assembling beta-hairpin peptide hydrogel is demonstrated to be an effective vehicle for the localized delivery of curcumin over sustained periods of time. The curcumin-loaded hydrogel is prepared in-situ where curcumin encapsulation within the hydrogel network is accomplished concurrently with peptide self-assembly. Physical and in vitro biological studies were used to demonstrate the effectiveness of curcumin-loaded beta-hairpin hydrogels as injectable agents for localized curcumin delivery. The gel-curcumin construct is first assembled into a solid gel and subsequently injected via syringe to a desired site, after which the material immediately becomes a solid again with almost identical properties to teh preinjection material. Notably, rheological characterization of the curcumin-loaded hydrogel before and after shear flow have indicated solid-like properties even at high curcumin payloads. In vitro experiments with a medulloblastoma cell line confirm that the encapsulation of the curcumin within the hydrogel does not have an adverse effect on its bioactivity. Most importantly, the rate of curcumin release and its conse- quent therapeutic efficacy can be conveniently modulated as a function of the concentration of the MAX8 peptide.
4:45 PM - LL5.5
Ultrashort Natural Aliphatic Tri- to Heptapeptides that Self-Assemble into Hydrogels for Biomedical Applications.
Archana Mishra 1 , Yihua Loo 1 , Charlotte Hauser 1 Show Abstract
1 , Institute of Bioengineering and Nanotechnology, Singapore Singapore
Various amphiphilic aliphatic peptides can self-assemble into hierarchical organizations like supramolecular scaffolds and gels. The effect of external stimuli, such as pH, concentration, heat, and solvent, on peptide self-assembly has provided insight in tuning these peptides to achieve different macromolecular scaffolds and nanostructures. Development of short and natural self-assembling peptides would be of added benefit in biomedical applications due to reduced cost and ease of scaffold fabrication. We have developed a novel class of rationally designed ultrashort (3 to 7 amino acids) amphiphilic peptides. To date, these are the smallest natural aliphatic peptides to self-assemble to form hydrogels1. These peptides have a characteristic sequence motif: an aliphatic amino acid tail of decreasing hydrophobicity capped by a polar amino acid head group at the C-terminus. Circular dichroism and X-ray fiber diffraction studies demonstrated that these ultrashort peptides self-assemble in water into fibrous hydrogel scaffolds (FESEM studies) by forming β-turn fibrils via α-helical transitions. These hydrogels are easy to fabricate and possess desirable properties such as high water content (< 99.9%) and thermal resistance (< 90ο C). The mechanical strength of these hydrogels (up to 90kPa) can also be tuned by various factors such as salts, peptide concentration, pH, and self-assembly time2. Considering their cost-effective synthesis and biocompatibility with various primary cells, these peptides can be applied in biomedical applications such as drug delivery and tissue engineering. References:1. Hauser, C.A.E. et al. PNAS (2011).2. Mishra, A., Loo, Y., Deng, R., et al. Nanotoday (2011)
5:00 PM - LL5.6
Self-Assembled Gels from Biological and Synthetic Polyelectrolytes.
Paul Calvert 1 , Skander Limem 1 , Dapeng Li 1 , Marc in het Panhuis 2 , Gordon Wallace 2 Show Abstract
1 , University of Massachusetts Dartmouth, N Dartmouth, Massachusetts, United States, 2 , University of Wollongong, Wollongong, New South Wales, Australia
Natural gels in plant and animal tissues are characterized by high strength and toughness compared to most synthetic gels. The diffusional properties of the natural gels must be crucial for allowing nutrients and control proteins to reach cells in the tissues but we know little about how diffusive transport relates to the microstructure of these gels. The intermolecular bonding in natural gels is mostly a combination of ionic and hydrogen bond with few covalent links. There are few good controlled methods for forming similar gels synthetically.Thin films of complexes of anionic and cationic polyelectrolytes have been made by layer-by-layer dipping for some time. These gels cannot be formed in bulk because direct mixing produces an inhomogeneous precipitate. We have succeeded in making thick films of these gels by inkjet printing alternate layers of the anionic and cationic components. This gives a thickness scale of about 100 nm-1 micron, making the process thousands of times faster than dipping methods. The inkjet approach also allows the relative proportions of anionic and cationic polymers to be changed, resulting in gels with different amounts of residual small ions. The films have been characterized for swelling behavior and diffusion properties of small molecules, polymers and proteins as a function of ion ratio.
5:15 PM - LL5.7
Predicting Sol-Gel Phase Behavior of Protein Physical Hydrogels through Molecular-Level Design and Characterization.
Widya Mulyasasmita 2 , Sarah Heilshorn 1 2 Show Abstract
2 Bioengineering, Stanford University, Stanford, California, United States, 1 Materials Science & Engineering, Stanford University, Stanford, California, United States
Predictable tuning of bulk mechanics from the molecular level remains elusive in many physical hydrogel systems due to the reliance on non-specific and non-stoichiometric chain interactions for network formation. We describe a Mixing-Induced Two-Component Hydrogel (MITCH) system, in which network assembly is driven by specific and stoichiometric peptide-peptide binding interactions. By integrating protein science methodologies with simple polymer physics models, we manipulate the polypeptide chain dynamics and demonstrate the direct ability to predict the resulting effects on network crosslinking density, sol-gel phase behavior, and gel mechanics. These hydrogels are composed of two recombinant protein polymers, each containing multiple repeats of complementary peptide domains. Multiple repeats of each peptide domain are concatemerized by hydrophilic spacers to form two block copolymers. Hydrogel network assembly is driven spontaneously by the specific recognition between these peptides with an exact 1:1 stoichiometry, thus allowing sol-gel transition to occur by simple mixing. While a suite of protein science methodologies is routinely available for molecular biology research, its capability has not been deeply exploited in the field of polymer technology. Recombinant protein polymer synthesis requires exact amino acid sequence specification, an advantage that enabled the creation of MITCH variants with different domain binding affinities and repeat frequencies. Using data from a variety of molecular characterization tools (dynamic light scattering, circular dichroism, and isothermal titration calorimetry) in conjunction with polymer physics models, we predicted the critical concentration for chain entanglement, the upper thermal limit of the sol-gel phase diagram, and the relationship between component stoichiometry and hydrogel storage modulus. These predictions were experimentally confirmed using passive micro-rheology, a high-throughput method for determining hydrogel viscoelasticity. These MITCH materials enable mammalian cell encapsulation at constant physiological conditions – a significant advantage over other hydrogels that are commonly used for cell encapsulation, such as collagen and Matrigel. These materials are currently being explored as cell-carriers to improve cell viability during stem cell transplantation procedures. In summary, we demonstrate how the coupling of protein science measurements with polymer physics theory can be used to translate dynamic chain interactions into macroscopic-level viscoelastic properties.
5:30 PM - LL5.8
Environmentally Friendly Adhesion on Wet Surfaces by Mussel Adhesive Protein Mimetic Polymer.
Jin Nishida 1 , Motoyasu Kobayashi 1 , Atsushi Takahara 1 Show Abstract
1 ERATO, JST, Fukuoka Japan
The mussel adheres to various surfaces (even polyethylene or teflon surface) in water by using marine adhesive protein (MAP). It is well known that mussel MAP specifically contains unusual amino acid 3,4-dihydroxyphenyalanine, which works as a cross-linking point and interact with surface to give strong adhesion. In the present work, we synthesized a water soluble poly(acrylamide) derivatives having dihydroxyphenyl groups and amino groups as a mussel MAP mimetic, and transformed to an adhesive hydrogel by aerobic oxidation. We demonstrated here that our MAP mimic hydrogel could be the strong adhesive of aluminum plates (see below). Two types of acrylamide derivatives containing Boc protected amino group and triethylsilyl protected dihydroxyphenyl group were synthesized and copolymerized with hydroxyethylacrylamide by AIBN initiator. Protective groups in the resulting copolymer were removed by acid hydrolysis. The obtained MAPs mimetic polymer was dissolved in phosphate buffer solution (pH=8.0) to proceed cross-linking reaction. The solution gradually became viscous under ambient air atmosphere to give a gel within 2 hours, while no gelation occurred under argon atmosphere. Addition of thyrosinase (catechol oxydase) to the copolymer aqueous solution enhanced gelation rate to afford a gel within 20 minutes. These results indicated that the cross-linking reaction of the synthesized MAP mimetic polymer was triggered by oxidation of dihydroxyphenyl moieties, which are similar to the cross-linking mechanism of natural MAP. The specimen consists of two aluminum substrates was bonded together by the MAP mimetic polymer solution in a lapped joint under humid air for 24 hours. The interfacial region between the two aluminum plates failed when the lap shear strength achieved to 0.34 MPa due to the the cohesive failure. 3,4-Dihydroxyphenyl group in the polymer shows strong interaction with metal oxide surfaces through chelate bond formation. Because of this interaction, polymer gel tightly adhered to the oxidized aluminum surface. Thus, the polymer gel collapsed prior to being peeled off from surface. H. Yamamoto reported adhesion of aluminum plates by synthesized MAP with native sequence (H. Yamamoto, J. Chem. Soc. Perkin Trans. I, 1987, 613). It was found that the lap shear strength of adhesion by our MAP mimetic polymer was almost same as the native sequence MAP.
LL6: Poster Session II
Wednesday AM, November 30, 2011
Exhibition Hall C (Hynes)
9:00 PM - LL6.1
Modeling Mechano-Mutable Materials Composed of Crosslinked Nanogels and Nanoparticles.
Isaac Salib 1 , Victor Yashin 1 , German Kolmakov 1 , Balaji S. Iyer 1 , Krzysztof Matyjaszewski 2 , Anna Balazs 1 Show Abstract
1 , University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 2 , Carnegie Mellon University, Pittsburgh, Pennsylvania, United States
Using computational modeling, we design polymeric nanocomposites whose structure and properties can be manipulated by application of a mechanical load. We consider a material that is composed of deformable nanogels and rigid nanoparticles that are crosslinked by labile linkages. Each linkage can encompass multiple parallel labile bonds. The individual units (nanogels and nanoparticles) are modeled via the lattice spring model (LSM), which is an efficient method for probing the response of materials to mechanical deformation. The crosslinks between the units are simulated via the modified hierarchical Bell model (MHBM), which allows us to capture how the rates of rupture and re-formation of multiple, parallel bonds depend on the applied force. Under small deformations, the material behaves as a linear viscoelastic solid, with the properties being dependent on the composition of the mixture and the spatial distribution of the two types of units. At large deformations, breakage of the labile crosslinks allows the nanoscopic units to rearrange within the material, and the formation of new crosslinks stabilizes new configurations of the units. We demonstrate that the application of repetitive, large scale deformations in alternating directions can lead to remarkable changes in the material’s structure, which, in turn, results in the enhancement of the elastic properties and strength of the material.
9:00 PM - LL6.10
Culturing Cells on Flexible Substrates of High Refractive Indexes.
Liou Yu Ren 1 , Kuo Po-Ling 1 Show Abstract
1 Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei City Taiwan
Mechanical cues in cellular microenvironment play a critical role in directing a class of cellular behaviors such as the dynamic of cell adhesion, migration, and differentiation. Several advanced optical techniques, such as total internal reflection fluorescence microscopy (TIRFM) and structured-illumination nano-profilometry (SINAP), have been developed for a better resolution of these dynamic processes. These techniques however require culturing cells on materials of refractive index close to that of glass, while most studies regarding the effects of mechanical cues on cellular dynamics were conducted on hydrogel-based substrates. Here we report the development of culturing substrates of tunable rigidity and refractive index suitable for TIRFM and SINAP. Polyvinyl chloride (PVC) based substrates were mixed with a softener called Di(isononyl) Cyclohexane-1,2-Dicarboxylate (DINCH). The volume ratio of PVC to DINCH was varied from 1:1 to 3:1. The mixture was cured by heating in a well-ventilated oven for 2h. The Young’s modulus of the resulting substrates was examined using a custom-made elastometer. The refractive index was measured by ultraviolet spectrum reflectance. The substrates were cultured with tumor cells CL1-5 and myoblasts C2C12. Cell viability was examined using the MTT assay. The dynamics of cell adhesion and filopodia activities were examined using TIRFM and SINAP, respectively. Preliminary results show that PVC mixed with DINCH yielding material stiffness of a wide, tissue-mimicking range. The resulting refractive index was close to 1.5. Our findings suggest that PVC based culturing substrates have a great potential in the application of TIRFM and SINAP based studies.
9:00 PM - LL6.12
Sergio de Rooy 1 , Ridgely Lodes 1 , Das Susmita 1 , Ioan Negelescu 1 2 , Joshua Monk 3 , Francisco Hung 3 , Isiah Warner 1 Show Abstract
1 Chemistry Department, Louisiana State University, Baton Rouge, Louisiana, United States, 2 School of Human Ecology, Louisiana State University, Baton Rouge, Louisiana, United States, 3 Department of Chemical Engineering, Louisiana State University, Baton Rouge, Louisiana, United States
Cyclodextrins (CDs) are a group of cyclic amylose compounds that consist of 6, 7, or 8 glucose units. Their toroid structure results in a hydrophobic cavity which allows for the formation of highly stable host-guest complexes with different analytes. This phenomenon has made CDs desirable for applications such as chemical separations, drug-delivery, and in food science. Ionic liquids (ILs) are organic salts that have low melting points. The wide solvation range of ILs has enabled the design of ionic liquid gels (ionogels) with organic, inorganic, and biobased materials. In the current study novel ionogels were prepared from a range of different CDs at various concentrations. Their rheological and thermal properties were investigated. In order to obtain a better understanding of the interaction between the ILs and the CDs at the molecular level, various fluorescent probes were employed, and 2D-NMR experiments and molecular modeling calculations were performed. The CD ionogels with their tunable rigidity may find possible applications in chiral separations and sensing.
9:00 PM - LL6.2
The Sol-Gel Transitions Observed in the Aqueous Solutions of Synthetic Amphiphilic PEG.
Akihiro Aso 1 , Kazutaka Taki 2 , Hitoshi Tamiaki 2 , Kazunori Toma 3 , Atsushi Hotta 1 Show Abstract
1 Graduate School of Science and Technology, Keio University, Yokohama, Kanagawa, Japan, 2 Institute of Science and Engineering, Ritsumeikan University, Kusatsu, Shiga, Japan, 3 , Asahi Kasei Corporation, Fuji, Shizuoka, Japan
Hydrogels have been widely investigated as cell culture scaffolds in a simulated body environment. Considering cell culture in a significantly different environment from in vivo experiment for medical assay by following a pathological model, it is important to control the gelation behavior in order to carry out the cell culture in three-dimension using hydrogels. In fact, the aqueous phase should be liquid sol when mixed with cells at room temperature, followed by the phase change into solid gel at the cell culturing temperature of 37 °C. Hence, the temperature-responsive copolymers which gelated at ~37 °C have been long desired for 3-D cell culture. A low-molecular-weight gelator, particularly an amphiphile with hydrophobic and hydrophilic moieties, has been a prospective candidate for the temperature-responsive copolymer, which can be effectively used for 3-D cell culture scaffolds especially in the tissue engineering field. The amphiphiles can self-assemble in an aqueous solution to form micellar structures presenting sol or gel features by changing the dispersed states of the micelles through molecular interactions such as hydrogen bonding and hydrophobic interaction in response to temperature. It is, however, often difficult to adjust the sol-gel transition temperature for the cell-culture applications simply by the molecular design of the gelators. In this study, diblock and triblock amphiphilic gallamides with hydrophobic alkyl chains and hydrophilic PEG moiety were synthesized. By mixing the diblock and the triblock amphiphiles, the mixed solution was found to become sol or gel over a wide range of temperature. When these two synthetic compounds were mixed at the molar ratios of the diblock to the triblock amphiphiles 55:45 in different concentrations (16, 17, 18 wt%), the resulting solution showed a thermoreversible sol-gel transition upon heating at ~37 °C, the normal core body temperature, indicating that the blend was potentially useful for 3-D cell culture. The 16 and 17 wt%-mixed solutions exhibited a liquid sol at low temperature, while a sol-gel transition occurred at 43 and 37 °C, respectively, upon heating, and hysteresis was observed in both cases. The effects of mixing of the sol and the gel on the macroscopic sol-gel transition behavior and the viscoelasticity were discussed. It was found that the dynamic moduli and the sol-gel transitions could be effectively controlled by changing the concentrations of the aqueous solution of the mixtures. The thermoreversible sol-gel transition behavior around 37 °C suggested that the system could be suitable for in–vitro 3-D cell culture scaffolds. The structural analyses were carried out to elucidate the underlying sol-gel transition mechanism of the mixture of the amphiphiles.
9:00 PM - LL6.3
Calcium Ions to Crosslink Supramolecular Nanofibers for Tuning the Elasticity of Hydrogels over Orders of Magnitude.
Junfeng Shi 1 , Yuan Gao 1 , Yue Pan 1 , Bing Xu 1 Show Abstract
1 , Brandeis University, Waltham, Massachusetts, United States
We report the use of calcium ions (Ca2+) to crosslink the nanofibers of self-assembled small peptides for tuning the elasticity of supramolecular hydrogels up to five orders of magnitude. Containing large amount of water and being soft, hydrogels bear striking physical resemblance to human tissues, which has resulted in intensive exploration of hydrogels as biomaterials for applications ranging from tissue engineering to drug delivery. The successful application of hydrogels not only requires certain biological functionalities to be incorporated in the hydrogels, but also demands proper elasticity of the hydrogels because the fate of the cells is sensitive to tissue level elasticity. We combine aromatic-aromatic and electrostatic interactions to tailor the elasticity of supramolecular hydrogels. At almost neutral pH, the hydrogelators and water form viscous solutions, which, upon the addition of calcium ions, turn to hydrogels. The storage moduli of the hydrogels increase drastically (i.e., orders of magnitude) with the relative small increase of concentration of calcium ions. In addition, the crosslinking density of the nanofibers in the hydrogel also increases with the concentration of calcium ions, indicating that the calcium ions participate both intrafiber and interfiber coordination. Besides reaching exceptional high moduli (up to 160000 Pa) at a quite low concentration of the hydrogelators (0.8 wt %), the hydrogels recover rapidly after mechanical deformation. Since there are increasingly clear and affirmative evidences suggesting the dependence of cellular behaviors on the mechanic properties of matrix or scaffolds, this work offer both insights and an alternative approach to develop soft nanomaterials for bioengineering and biomedical applications.
9:00 PM - LL6.4
Preparation and Properties of Chitosan-Alginate Janus Hydrogels.
Sunae Hwang 1 , Kyoung Duck Seo 2 , Suk Tai Chang 1 , Dong Sung Kim 2 , Jonghwi Lee 1 Show Abstract
1 , Chung-Ang University, Seoul Korea (the Republic of), 2 , Pohang University of Science and Technology, Pohang Korea (the Republic of)
Anisometric structures of materials have attracted intense research interests since they are considered to be able to open up novel capabilities and related applications. In here, chitosan-alginate Janus particles were prepared by ionic gelation for the development of biocompatible embolic particles. Chitosan, a cationic polysaccharide, were complexed with sodium alginate, an anionic polysaccharide in Janus hydrogels, where gold nanoparticles stabilized by chitosan were incorporated for CT (computed tomography) systems. By using a polypropylene mesh, chitosan and alginate solution could be located at opposite sites facing each other. Due to the ionic interactions between chitosan and alginate, the interface between the two compartments of Janus structures did not suffer from interfacial failure problems. Stereoscopic microscopy revealed the successful preparation of Janus particles. From the transmission electron microscope (TEM) and UV-vis spectrophotometry studies, stabilized gold nanoparticles were confirmed and used as CT markers in the hydrogels. Chitosan-alginate Janus particles showed self-aggregation behavior through their own surface charges, which was dependent on various external stimuli such as pH, and salt concentrations. Apparently, the disc-like shape of these particles promoted the formation of complete self-aggregated hydrogel clusters. These particles could provide intelligent functionality to the current embolization technology and other particle applications.
9:00 PM - LL6.5
Supramolecular Hydrogel of a Versatile Ligand of Metal Ions.
Yue Pan 1 , Junfeng Shi 1 , Bing Xu 1 Show Abstract
1 Chemsitry, Brandeis, Waltham, Massachusetts, United States
We report the use of a common ligand, nitrilotriacetic acid (NTA), for generating molecular hydrogels to explore the design principle and scope of metal-ligand interactions in soft materials. NTA, a well-established ligand for coordinating with metal ions, conjugates with small peptides to form a novel supramolecular hydrogelator. This hydrogelator, besides to afford a hydrogel as an efficient absorber of metal ions, form a magnetorheological hydrogel upon binding magnetic nanoparticles or paramagnetic rare earth metal ion. This work support that the cooperative stabilization, provided by pi-pi interactions, hydrogen bonding, and metal-ligand bond, is a powerful strategy for developing soft materials. In addition, the principle validated in this work should be applicable for the development of other hydrogels that use metal-ligand coordination bonds for developing catalytic materials.
9:00 PM - LL6.6
Investigation of Cytotoxicity of Di-Phenylalanine Based Hydrogelators.
Yi Kuang 1 , Gaolin Liang 2 , Yuan Gao 1 , Fan Zhao 1 , Bing Xu 1 Show Abstract
1 , Brandeis University, Waltham, Massachusetts, United States, 2 , University of Science and Technology of China, Hefei, Anhui, China
Di-phenylalanine is a widely used hydrogelator motif in supramolecular hydrogelation. Despite the many works on hydrogelation ability of molecules consisting of di-phenylalaine, study of cytotoxicity of them is limited. We report the investigation of cytotoxicity of hydrogelators and their enzymatic precursors based on di-phenylalaine motifs of different isomers of phenylalanine. Overall, the precursors with a phosphate group exhibit higher cytotoxicity than their corresponding hydrogelators for all precursor/hydrogelator pair; molecules with β-phenylalanine always have lower cytotoxicity than their α counterpart. Among all molecules investigated, precursor (3b), consists of two β3-L-phenylalanine and one α-L-tyrosine-phosphate, shows exceptionally high cytotoxicity for both cancer cells (HeLa) and normal cells (Ect1) which is resulted from both low degradation rate of β-amino acid and the outstanding intracellular hydrogelation ability of 3b. The cytotoxicity study of di-phenylalaine motif will facilitate the design and exploration of cell targeting hydrogelators that have desired toxicity on cells.
9:00 PM - LL6.7
Enzymatic Formation of Molecular Hydrogels of Adenosine Nucleoside.
Xuewen Du 1 , Junfeng Li 1 , Yuan Gao 1 , Yi Kuang 1 , Bing Xu 1 Show Abstract
1 , Brandeis University, Waltham, Massachusetts, United States
Here we report the design, synthesis, and characterization of molecular hydrogels consisting of adenosine nucleoside. We connect adenosine 5′-monophosphate (AMP) onto motif of an effective hydrogelator (NapFFK) and use alkaline phosphatase (ALP) to instruct the self-assembly of the nucleopeptides of adenosine in water for developing molecular nanofibers/hydrogels. Since nucleotide phosphates, such as ATP, bound to actin monomers influence assembly of actins into filaments, this AMP-based hydrogels may lead a novel biomaterial that interact with actins—a pivotal cytoskeleton protein.
9:00 PM - LL6.8
Non-Steroidal Anti-Inflammatory Drugs (NSAID) Containing Multifunctional Supramolecular Hydrogels.
Jiayang Li 1 , Junfeng Shi 1 , Yuan Gao 1 , Yi Kuang 1 , Bing Xu 1 Show Abstract
1 Chemistry, Brandeis University, Waltham, Massachusetts, United States
Here we report a new type of supramolecular hydrogelators made of non-steroidal anti-inflammatory drugs (NSAID) and small peptides. The conjugation of NSAIDs and small peptides, such as Phe-Phe, generates molecules that self-assemble in water to form molecular nanofibers as the matrices of hydrogels. As a useful member in NSAIDs, naproxen conjugates with Phe-Phe to give a promising hydrogelators (NpxFF) that also serves as a general motif to enable enzymatic hydrogelation in which the conversion of a precursor to a hydrogelator by a phosphatase results in a hydrogel at a physiological condition. Except aspirin, the conjugates of Phe-Phe with other NSAIDs, for example, (R)-flurbiprofen, racemic flurbiprofen and racemic ibuprofen, are able to form supramolecular hydrogels. This approach is a potential alternative to polymeric hydrogel-based drug delivery media and contributes to the development of bioactive molecules that have dual or multiple roles, such as hydrogelators and therapeutic agents.
9:00 PM - LL6.9
Multiple Enzyme-Instructed Intracellular Formation of Nanofibers/Hydrogels for Selective Inhibition of Cancer Cells.
Dan Yuan 1 , Keming Xu 2 , Zhimou Yang 2 , Gaolin Liang 2 , Chun Liang 2 , Zhihong Guo 2 , Bing Xu 1 Show Abstract
1 Chemistry, Brandeis University, Waltham, Massachusetts, United States, 2 , The Hong Kong University of Science and Technology, Hong Kong China
We report a new approach to inhibit the growth of cancer cells. The over-expressed esterases and phosphatases and high metabolic rates in cancer cells allow us to design molecules that are both the substrates of esterases and/or phosphatases and the precursors of hydrogelators, which self-assembles to form nanofibers intracellularly. We observed the enhancement of self-assembly of small molecules by intracellular enzymes and the formation of nanofibers that were specifically stained by Congo red. By substituting the precursors with unnatural amino acid to increase their intracellular stability, we increased the potency of the precursors against cancer cells up to 5 × by designing precursors with multiple sites for enzymatic cleavage, we increased the selectivity of the precursors toward cancer cells at broader concentration ranges. In the process of hydrogelation induced cytotoxicity, the self-assembly and hydrogelation of hydrogelators induced high cellular stress, which led to the death of cancer cells. These findings promise a general strategy for targeted cancer therapy by utilizing regulated self-assembly of small molecules and exploiting high metabolic rate of cancer cells.
Ferenc Horkay National Institutes of Health
Noshir Langrana Rutgers University
J. David Londono Dupont de Nemours and Co.
Wilhelm Oppermann Clausthal University of Technology
Richard G. Weiss Georgetown University
LL7: Theory and Modeling
Wednesday AM, November 30, 2011
Room 101 (Hynes)
9:30 AM - **LL7.1
Colloidal Gels: Insight from Numerical Studies.
Francesco Sciortino 1 Show Abstract
1 Physics, Sapienza Universita' di Roma, Rome Italy
In the last years we have witnessed significant progress in the understanding of the aggregation properties of patchy colloidal particles and of the process of formation of equilibrium gels. In the talk I will discuss how the number of patches (a variable which can be experimentally controlled in current synthesis procedures) affects the equilibrium phase diagram and the relative stability against decomposition into two phases with different colloidal concentration, the analog of the gas-liquid phase separation in simple liquids. For small number of patches, the liquid phase exists as an equilibrium state down to small temperatures, giving rise to empty liquids and equilibrium gels.Finally, I will discuss the connection between irreversible and reversible gelation in this class of colloidal systems proposing a conceptual link between elapsed time during the aggregation kinetics and temperature in thermodynamic equilibrium.Relevant literature includes:E. Bianchi et al Phase diagram of patchy colloids: towards empty liquids Phys. Rev. Lett. 97, 168301, 2006FS et al, A parameter-free description of the kinetics of formation of loop-less branched structures and gelsSoft Matter 5, 2390-2398 (2009)Barbara Ruzicka et al Observation of empty liquids and equilibrium gels in a colloidal clay Nature Materials 10, 56-60 (2011)
10:00 AM - **LL7.2
Dynamics of Polyelectrolyte Gels.
Murugappan Muthukumar 1 Show Abstract
1 , University of Massachusetts, Amherst, Massachusetts, United States
The dynamics of polyelectrolyte gels emerge from the collective aspects of entropy of polymer strands, quenched degrees of freedom from crosslinks, electrostatic interactions among charged monomers, and counterion entropy. Recent experiments and a theory will be presented regarding density fluctuations in polyelectrolyte gels. The pretransitional slowing down of collective dynamics as the system approaches a first order volume phase transition will be discussed.
11:00 AM - **LL7.3
Intermolecular Packing Preferences and Polymorph Predictions for Select Organic Gelators.
Miklos Kertesz 1 , Wenzhuo Li 1 , Michael Roumanos 1 , Richard Weiss 1 , Saul Lapidus 2 , Peter Stephens 2 Show Abstract
1 Chemistry, Georgetown University, Washington, District of Columbia, United States, 2 Physics Department , Stony Brook University, Stony Brook, New York, United States
Molecular aggregation in fibrous gel formation is affected by molecular conformation and intermolecular interactions. Crystal structure prediction remains challenging. [1,2] Our strategy of modeling crystalline aggregation is based on a multi step process that involves the following elements: (a) conformational search based on quantum mechanical and/or force field optimization; (b) optimization of structures of low energy small aggregates (typically dimers); (c) polymorph prediction based on low energy conformers and aggregates. Conformational analysis is based on separating the molecules into rigid and non-rigid segments. In the end of this multi step process we generate a list of viable crystal structures (LVCS). The modeling is supplemented by extensive validation based on analogues available in the Cambridge Structural Database (CSD). This validation based on analogues is used to reduce the list of conformers and the list of small aggregates. In steps (b) and (c) we further reduce the LVCSs by eliminating similar items on the list (“clustering”). Key component of the method is comparison with experimentally determined power X-ray diffraction (PXRD) patters obtained at Stony Brook University. When available, we utilize unit cell parameters in order to further narrow down the LVCSs. These modeling steps are applied for the organic gelators, 3β-cholesteryl N-(2-naphthyl) carbamate (CeNC) and 5α-cholestan-3β-yl N-(2-naphthyl) carbamate (CNC). Similarity analysis is used to reveal the structural reasons for the preferences for different crystal structures between CNC and CeNC. Day, G.M.; Cooper, T.G.; Cruz-Cabeza, A.J. et al. Acta Crystallogr. B. 2009, 65, 107-125. Materials Studio, Accelrys® Software Inc. “Accelrys Materials Studio.” 2009, http://accelrys.com/products/materials-studio.(a) Huang, X.; Terech, P.; Raghavan, S. R.; Weiss, R. G. J. Am. Chem. Soc. 2006, 128, 15341-15352; (b) Huang, X.; Terech, P.; Raghavan, S. R.; Weiss, R. G. J. Am. Chem. Soc. 2005, 127, 4336-4344.
11:30 AM - LL7.4
Micro- to Mesoscale Simulation of Hydrogel Swelling Dynamics Based on a Phase Field Model.
Heike Emmerich 1 , Daming Li 1 Show Abstract
1 , University of Bayreuth, Bayreuth, Bavaria, Germany
Hydrogels consist of three-dimensional charged polymer networks, mobile ions, and solvent, and they are usually synthesized by chemically cross-linking charged polymers. Hydrogels can swell or shrink by the absorption or squeeze of solvent if it is under the external stimuli, e.g., temperatures, pH, ionic strength, etc. Stimuli-response hydrogels have attracted much attention for their potential in wide range of applications, e.g. drug delivery, biosensors, tissue engineering etc.Here we contribute to a precise understanding of the mechanisms responsible for the hydrogels’ swelling kinetics as well as dynamics by proposing for the first time a model approach that can resolve the inherent short range correlation effects along the hydrogel-solution interface jointly with the long range ionic transport fields. To that end we investigate the swelling dynamics of hydrogels, which is a moving boundary problem, by a phase field model, which couples the Nernest- Planck like equation for the concentration of mobile ions, Poisson equation for the electric potential, mechanical equation for the displacement and an equation for the phase field variable.Simulation reveals that under the chemical stimulation the hydrogel will swell or shrink if the concentration of mobile ions inside bath solution decreases or increases.This is in agreement with the experimental results qualitatively.
11:45 AM - LL7.5
Modeling Photoinduced Morphing and Directed Motion of Polymer Gels.
Olga Kuksenok 1 , Anna Balazs 1 Show Abstract
1 Chemical Engineering Dep, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
We develop a computational model to simulate the behavior of photo-responsive polymer gels that contain spirobenzopyran (SP) chromophores. Using this model, we design three-dimensional samples with dynamically reconfigurable morphologies and photo-induced motility. In the dark, the SP moieties assume an open ring conformation and are hydrophilic; under illumination with blue light, the chromophores assume a closed ring conformation and are hydrophobic. Importantly, the collapse of the gels is caused by the decrease in hydration due to conformational changes and not by a light-induced heating of the polymer network. We first validate our model by by focusing on relatively small samples and calculating the variation in the degree of swelling for gels illuminated by uniform light of a given intensity and for non-illumuminated gels that undergo temperature-induced volume phase transitions. We show good agreement between our results and available experimental data on volume phase transitions in these systems. We then demonstrate that these gels can be effectively “patterned” remotely and reversibly with light (by, for example, illuminating the sample through photomasks) and thus, we can produce a variety of morphologies with features sizes that are on the sub-mm to mm length scale. This distinctive patterning and the ability to re-configure the same sample into a variety of shapes would not be feasible in systems where light causes the heating of the samples because thermal diffusion occurs much faster than the collective diffusion of the polymer network. We also show that by introducing variations in crosslink density within the gels during their preparation, as well as introducing temperature gradients, we have additional means of guiding the dynamic behavior of these versatile, responsive systems. We then demonstrate that one can use a mobile light source to move multiple gel pieces to a specific location and then merge these pieces into an extended, three-dimensional structure. The results point to a novel method for controlling the self-organization of soft, reconfigurable materials.
12:00 PM - LL7.6
Agglomeration Dynamics in Thermo-Sensitive Polymers across the Lower Critical Solution Temperature: A Molecular Dynamics Simulation Study.
Sanket Deshmukh 1 , Derrick Mancini 1 2 , Subramanian Sankaranarayanan 3 Show Abstract
1 CNM, Argonne National Lab, Lemont, Illinois, United States, 2 APS, Argonne National Lab, Lemont, Illinois, United States, 3 CNM, Argonne National Lab, Lemont, Illinois, United States
Stimuli-sensitive polymers can respond to surrounding environmental changes such as pH, temperature, light, glucose etc. that can lead to change in their conformations. Conformational changes in these polymers can be controlled/altered by using different co-monomers, additives etc. Temperature sensitive polymers either have an upper critical or a lower critical solution temperature (UCST or LCST). Poly(N-isopropylacrylamide), a classical thermo-sensitive polymer, has an LCST at ~32°C. PNIPAM polymer chains are soluble below the LCST and insoluble above the LCST. If the concentration of PNIPAM is >1 ppm, then polymer chains after undergoing coil-to-globule transition above the LCST, aggregates to yield a stable colloidal dispersion. However, to-date the atomic scale mechanism and structure of these aggregates is not clear. Different parameters, such as minimum distance between two polymer chains, number of monomers/polymer chains needed to form such agglomerates, have not yet been studied. Dynamical properties of these agglomerates and water below and above the LCST can be studied using molecular dynamics (MD) simulations. Two PNIPAM chains, consisting of 30 monomer units each, were placed in a simulation cell and were subsequently solvated. Simulations were carried out below and above the LCST, namely at 278 and 310K for 20ns. Simulated trajectories were analyzed for structural and dynamical properties of both PNIPAM and water. We observe coil-to-globule transition in PNIPAM above the LCST. We also find that the PNIPAM chains agglomerate above the LCST. However, we do not see any agglomeration in PNIPAM chains below the LCST. Diffusion coefficient for water molecules was calculated, using Einstein’s relation, both below and above the LCST. We observe lowering in the diffusion coefficient of water below the LCST. We also study agglomeration of 5 PNIPAM chains each consisting of 5 monomer units. There was no significant difference in polymer agglomeration behavior across the LCST for these short chain oligomers. The agglomeration behavior is thus strongly correlated to the size of the polymer chains. This study provides fundamental insights into the atomistic scale mechanism of PNIPAM agglomeration and transport properties of polymer/water across the LCST.
12:15 PM - LL7.7
Modeling Self-Healing in Networks of Star-Shaped Nanogel Particles.
Balaji Iyer 1 , Isaac Salib 1 , Victor Yashin 1 , German Kolmokov 1 , Krzysztof Matyjaszewski 2 , Anna Balazs 1 Show Abstract
1 Chemical And Petroleum Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 2 Department of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States
We report the results of a computational study of the deformation, fracture, and self-healing processes in a network composed of star-shaped nanogel particles. Each particle consists of a permanently cross-linked elastomeric core and a corona of flexible chains grafted chemically to the core surface. The corona chains are assumed to contain functional groups that can form either stable or multiple labile bonds between the overlapped coronas of neighboring nanogel particles. In the resulting network, under a sufficiently high deformation, the stable bonds between the corona arms break irreversibly, whereas the labile bonds break and reform at a specific rate that depends on the applied force. We demonstrate that the presence of stretchable corona arms increases the material’s strength and enhances self-healing. In particular, we show that the stretchable corona arms enable the nanogel rearrangements that result in distinct necking phenomena. In the course of necking, labile bonds form in the direction normal to that of stretching and consequently enhance self-healing. Our results reveal that while the stress at break is proportional to the multiplicity of the labile bonds, N, the ductility is a more complex function of N that exhibits a maximum depending on the structural characteristics of the network.
12:30 PM - LL7.8
Mesoscale Simulation of the Structure of Star Acrylated Poly(Ethylene Glycol-co-lactide) Hydrogels.
Seyedsina Moeinzadeh 1 , Esmaiel Jabbari 1 Show Abstract
1 Chemical Engineering, University of South Carolina, Columbia, South Carolina, United States
Introduction: Poly (ethylene glycol-co-lactide) (PEL) copolymers have been used extensively for the synthesis of hydrogels for tissue engineering applications. PEL macromers can be functionalized with acrylate groups to produce chemically crosslinked degradable hydrogels. PEL macromers are potentially useful as injectable in situ crosslinkable cell carriers in tissue engineering and regenerative medicine. The viability and function of cells encapsulated in these macromers depends on crosslink density, water content, and gel remodeling (degradation rate), which in turn, depend on the distribution, concentration, and accessibility of the acrylate groups in the macromer. The star PEL macromers have higher density of acrylate groups per chain and lower shear viscosity, compared to the linear macromers, thus increasing the rate of crosslinking and reducing the minimum required concentration of initiator. The objective of this work was to simulate the structure of acrylate-functionalized PELA (SPELA) at the mesoscale using the Dissipative Particle Dynamics (DPD) approach and predict the effect of lactide (LA) to EG ratio on the microstructure of the macromer in aqueous solution.Methods: A 4-arm star PEG macromer with molecular weight of 5 kDa was used followed by the lactide block, with each arm terminated with an acrylate group. The system components were coarse-grained into different beads (set of atoms) which moved according to Newton’s equations of motion integrated via a modified Velocity-Verlet algorithm. The force acting on each bead, in a specific cutoff distance (rc), was divided into conservative force (FC), random force (FR), dissipative force (FD), bond force (FS) and bond angle force (FE). The repulsion parameters of the conservative force (αij) were calculated from the solubility parameters of different beads, each of which were extracted from an atomistic molecular dynamics simulation (MD).Results: The acrylated 4-arm PEG was soluble in aqueous solution. As lactide was added to arm, a micellar structure was formed with the lactide and acrylate beads forming the core and the EG blocks extending through the aqueous solution. The micelles showed an increasing trend in size and decreasing trend in number density with increasing LA to EG ratio. Although the overall amount of acrylate in each micelle increased with LA volume fraction, the acrylate density decreased from the center to the surface of the micelles. In addition, the number of acrylate beads adjacent to a water bead decreased with increasing LA volume fraction, which indicated that the accessibility of acrylates to water (for crosslinking) decreased with increasing LA volume fraction. Conclusion: Results demonstrate that the LA to EG ratio in SPELA macromer significantly affects accessibility of acrylate groups in the aqueous phase and the extent of crosslinking.
12:45 PM - LL7.9
Multiscale Poroelastic Characterization of Hydrated Hydrogels via Indentation.
Zeynep Kalcioglu 1 , Roza Mahmoodian 1 , Yuhang Hu 2 , Zhigang Suo 2 , Krystyn Van Vliet 1 Show Abstract
1 DMSE, MIT, Cambridge, Massachusetts, United States, 2 School of Engineering and Applied Sciences, Kavli Institute, Harvard University, Cambridge, Massachusetts, United States
Indentation is a powerful means for characterization of very compliant materials such as gels and soft tissues which exhibit a wide range of time-dependent responses. Recently contact mechanics has been utilized to develop approaches to distinguish between poroelastic and viscoelastic regimes using load relaxation experiments, and to simultaneously extract the mechanical and transport properties of gels. These methods have been applied to experiments performed at macroscale. Since poroelastic relaxation times scale quadratically with contact size, use of large probes requires hours for a single load relaxation experiment to complete. For degradable materials such as biodegradable hydrogels and soft biological tissues, it is necessary to minimize the required experimental time. In this study, we investigated the applicability of these methods at small (micron) length scales to shorten relaxation times. We conducted load relaxation experiments on hydrated polyacrylamide (PAAm) gels at microscale via atomic force microscopy (AFM) - enabled indentation, as well as at macroscale using instrumented indentation. We confirmed the approach as a reliable means to distinguish between viscoelastic and poroelastic relaxation regimes at microscale. We extracted shear modulus G, drained Poisson’s ratio νs, diffusivity D, and intrinsic permeability κ of the gel for both length scales and found marked agreement between the properties obtained at micro- and macroscale levels, now accessed within seconds in the former rather than hours in the latter scenario. Our results demonstrate the promise of contact-based analysis of load relaxation response in poroelastic materials toward fast and robust characterization of their mechanical and transport properties.
LL8: Synthesis and Characterization of Polymer Networks
Wednesday PM, November 30, 2011
Room 101 (Hynes)
2:30 PM - **LL8.1
Chain Dynamics in Multicomponent Polyelectrolyte Solutions and Its Relation to Deformation Mechanism in Double Network Hydrogels.
Wen-li Wu 1 , Sanghun Lee 3 1 , Vijay Tirumala 1 , Michihiro Nagao 1 , Taiki Tominaga 2 1 , Tasuku Nakajima 2 1 , Jian Ping Gong 2 Show Abstract
1 , NIST, Gaithersburg, Maryland, United States, 3 , Seoul National University, Seoul Korea (the Republic of), 2 , Hokkaido University, Sapporo Japan
Double-network hydrogels (DN-gels) prepared from the combination of a moderately crosslinked anionic polyelectrolyte (poly 2-acrylamido-2-methyl-1-propanesulfonic acid, PAMPS) and a loosely crosslinked neutral polymer (polyacrylamide, PAAm) show strong mechanical properties far superior to that of their individual constituents. To determine the origin of the superior properties of DN-gels we investigated the structure and the chain dynamics of model PAMPS/PAAm solution blends using small angle neutron scattering and neutron spin echo measurements. Akcasu’s dynamic scattering theory for multicomponent system is modified to include long range interactions among polyelectrolytes, the resulted equation describes well the neutron spin echo results over the entire wave vector range covered in our experiments. Hydrodynamic interaction contributes significantly to the chain dynamics in high q regime. The implications of the above observation to the toughening mechanism in DN-gels will be discussed.
3:00 PM - **LL8.2
Structure and Properties of High Performance Gels Made by Module Assembling Method.
Mitsuhiro Shibayama 1 , Hanako Asai 1 , Kenta Fujii 1 , Takamasa Sakai 2 Show Abstract
1 Institute for Solid State Physics, The University of Tokyo, Kashiwa, Chiba, Japan, 2 Department of Bioengineering, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Recently, we developed a new class of biocompatible high-strength hydrogels, consisting of four-arm poly(ethylene glycol) (PEG) networks (hereafter we call Tetra-PEG gels). The Tetra-PEG gels are made by end-cross-coupling of two kinds of four-arm PEG having different functional groups at chain ends. Since the functional groups are amine group (TAPEG) and N-hydroxysuccinimidyl ester group (TNPEG), the coupling reaction occurs exclusively between TAPEG and TNPEG. Thus, a network with a functionality of four is prepared. The mechanical propertied of Tetra-PEG gel are much superior to those of conventional gels and the compressive strength of resulting gel was in a MPa range which was much superior to those of agarose gels or acrylamide gels having the same network concentrations. The mechanical energy dissipation was extremely low (tan δ ≈10-4). The macroscopic stress–strain relationship of the Tetra-PEG gels was in good agreement with that of microscopic elastic blobs. The maximum breaking strength was extremely high (≈ 27 MPa). The structure of Tetra-PEG gel was investigated by means of small angle neutron scattering (SANS) as a function of the polymer volume fraction, Φ0, and the molecular weight. The scattering functions could be represented by a simple Ornstein-Zernike function, indicating homogeneous network structure without cross-linking inhomogeneities. Hence, both the mechanical properties and the structural investigation lead to the conclusion that Tetra-PEG gels can be treated as uniformly packed elastic blobs with an extremely small fraction of network defects, such as dangling chains and trapped entanglements. Furthermore, various applications of Tetra-PEG gel, including biomedical applications and tetra-PEG ion-gel with high conductivity with extremely low volatility, will be addressed.