Mechanically Robust, Rapidly Actuating, and Biologically Functionalized Macroporous Poly( N -isopropylacrylamide)/Silk Hybrid Hydrogels (original) (raw)
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Nanofabrication Technologies, 2003
Sandia is exploring two classes of integrated systems involving bioactive materials: 1) microfluidic systems that can be used to manipulate biomolecules for applications ranging from counter-terrorism to drug delivery systems, and 2) fluidic systems in which active biomolecules such as motor proteins provide specific functions such as active transport. An example of the first class involves the development of a reversible protein trap based on the integration of the thermally-switchable polymer poly(N-isopropylacrylamide)(PNIPAM) into a micro-hotplate device. To exemplify the second class, we describe the technical challenges associated with integrating microtubules and motor proteins into microfluidic systems for: 1) the active transport of nanoparticle cargo, or 2) templated growth of high-aspect ratio nanowires. These examples illustrate the functions of bioactive materials, synthesis and fabrication issues, mechanisms for switching surface chemistry and active transport, and new techniques such as the interfacial force microscope (IFM) that can be used to characterize bioactive surfaces.
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Angewandte Chemie-international Edition, 2007
The development of materials that undergo shape changes occupies a central theme in materials science and has proven important in several applications. Several classes of hydrogels, which are cross-linked water-soluble polymers, can change their properties (such as, volume, cross-link density) in response to temperature, pH value, or ionic strength. These dynamic hydrogels can also be modified with biochemical moieties to give materials that change their properties in response to proteins and ligands. For example, hydrogels that undergo volume changes because of antigen-antibody and lectin-carbohydrate interactions have been used as biosensors. The underlying principle of operation of dynamic hydrogel materials relates to a change in their physical or chemical cross-linking density in response to environmental cues. An unexplored alternative to these approaches relies on the use of a natural protein that undergoes a conformational change as a mechanism to alter the characteristics of a material. The functional importance of protein motions in biological systems, together with the wide range of protein motions that can be harnessed, offers a flexible approach to the preparation of dynamic materials.
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Integrative nanobiotechnology utilizes natural ideas and materials for manufacturing nanoscale devices. As living organisms traditionally represent a good model for engineers to learn from, biological components of interest, with optimal functionality, have been used in the creation of biotic/abiotic hybrid devices. As an example, bacteriorhodopsin/F 0 F 1 -ATP-synthase-incorporated polymer vesicles provide a model of hybrid protein/artificial synthetic membrane system to perform biological functions. Some potential applications are the construction of intervesicular/intravesicular communications, such as excitable vesicles (EVs), for biocomputer and biomolecular motorpowered nanoelectromechanical systems (NEMS) for nanomedicine. Finally, advanced biotic/abiotic hybrid technology is expected to provide an alternative method to conventional fabrication technology to meet the increasing demands by saving enormous engineering efforts.
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Spatiotemporal control over engineered tissues is highly desirable for various biomedical applications as it emulates the dynamic behavior of natural tissues. Current spatiotemporal biomaterial functionalization approaches are based on cytotoxic, technically challenging, or non-scalable chemistries, which has hampered their widespread usage. Here we report a strategy to spatiotemporally functionalize (bio)materials based on competitive supramolecular complexation of avidin and biotin analogs. Specifically, an injectable hydrogel is orthogonally post-functionalized with desthiobiotinylated moieties using multivalent neutravidin. In situ exchange of desthiobiotin by biotin enables spatiotemporal material functionalization as demonstrated by the formation of long-range, conformal, and contra-directional biochemical gradients within complex-shaped 3D hydrogels. Temporal control over engineered tissue biochemistry is further demonstrated by timed presentation and sequestration of growth ...
Responsive polymers for dynamic modulation of bio-macromolecular transport properties
2008
Responsive self-assembling polymers are used in wide range of applications in the food, pharmaceutical, agricultural, electronic and environmental industries, as well as in the biomedical field. The proper design of such polymers is critical for the particular applications being considered. In this thesis, different matrices that can be modulated dynamically by the application of appropriate stimuli were designed and used for two applications: electrophoretic separation and gene transfection. Light represents an attractive trigger to change the properties of a polymer solution because it enables structural transitions to be induced under isothermal conditions without the addition of other chemical species to the solution, and is externally reversible and hence amenable to device design and automation. Amphiphilic copolymers with azobenzene moieties are of interest because the azobenzene can undergo reversible trans-cis photoisomerization leading to conformational isomers with significantly dissimilar dipole moments and hydrophobicities and thus different propensities to aggregate into nanoscale structures in aqueous media. Copolymers of 4methacryloyloxyazobenzene (MOAB) and N,N-dimethylacrylamide aggregate strongly in aqueous solutions with concentration-dependent aggregate size distributions and welldefined boundaries between the dilute and semi-dilute regimes. The copolymers are strongly surface active, an uncommon observation for random copolymers, and exhibit pronounced photoviscosity effects at higher concentrations. Trans-to-cis isomerization under UV light leads to partial dissociation of the azobenzene aggregates that form physical crosslinks, thereby significantly affecting the polymer solution rheology, with a consequent tenfold loss of viscoelasticity upon irradiation, especially in concentrated polymer solutions. Photo-responsive poly(N,N-dimethylacrylamide-co-methacryloyloxyazobenzene) (MOAB-DMA) and temperature-responsive Pluronic F127 (PF127) copolymers were blended to obtain mixed micellar systems that were responsive to both stimuli. The azobenzene groups of DMA-MOAB in the trans conformation self-associate and the interactions with PF127 are less pronounced when compared to those with cis conformation of the azobenzene groups. The cis-isomer of the MOAB-DMA copolymer self-associates less strongly than does the trans conformation, and thus the copolymer micelles dissociate upon UV irradiation. These polymeric unimers can form mixed micelles with the PF127 present. This causes the sol-gel transition temperature of the MOAB-DMA/PF127 blend to be 2-6 degrees lower upon UV irradiation than under dark conditions depending on the molar ratio of the two polymers. It has been found that I would like to express my gratitude to all those who have helped me to get to this stage. I am grateful to my advisors T. Alan Hatton and Kenneth A. Smith for giving me the opportunity to work in their group. Alan has helped me become a better researcher by letting me explore my ideas. I would also like to thank my thesis committee members, Prof. William Deen, Prof. Patrick Doyle and Prof. Daniel Wang for all of their contributions during my committee meetings. I am highly indebted to Dr. Lev Bromberg for his help with my research and for lending his time and effort for discussing my research problems even amidst his long lists of other commitments. I would also like to thank Hatton group members past and present for their help. In particular, I would like to thank Lino Gonzalez for imparting me some of his knowledge of optics and Comsol, and Sanjoy Sircar and Huan Zhang for timely discussions. I am also grateful to Harpreet, Saurabh and Abhinav for all their help and chats, which were a good break from research and how could I not mention: allowing me to gorge on their home-made food. I want to extend my thanks to my collaborators Prof.
An aptamer-functionalized chemomechanically modulated biomolecule catch-and-release system
Nature Chemistry, 2015
The efficient extraction of (bio)molecules from fluid mixtures is vital for applications ranging from target characterization in (bio)chemistry to environmental analysis and biomedical diagnostics. Inspired by biological processes that seamlessly synchronize the capture, transport and release of biomolecules, we designed a robust chemo-mechanical sorting system capable of the concerted "catch and release" of target biomolecules from a solution mixture. The hybrid system is composed of target-specific, reversible binding sites attached to microscopic fins embedded in a responsive hydrogel that moves the cargo between two chemically-distinct environments. To demonstrate the utility of the system, we focus on the effective separation of thrombin by synchronizing the pH-dependent binding strength of a thrombin-specific aptamer with volume changes of the pH-responsive hydrogel in a biphasic microfluidic regime, and show the non-destructive separation with quantitative sorting efficiency, system's stability and amenability to multiple solution recycling. Numerous biological processes involve the synchronized trapping, transporting, and sorting of specific biomolecules within complex fluids. 1 These processes arise from a chemo-mechanically modulated inherent integration of molecular recognition, reconfiguration and micromechanical motion of components in response to various internal signals. 1, 2 In contrast, current techniques for biomolecule sorting often require significant, even destructive, biomolecule modification, many sequential steps, and high energy input from lasers, sources of electrical, IR, or magnetic fields. 3-8 Considerable effort has recently been devoted to developing dynamic micro-and nano-scale hybrid systems that exploit the precise geometry of their components, combine chemical and mechanical action, act in a multimodal fashion, and even generate autonomous movement or
Natural extracellular matrix (ECM) consists of complex signals interacting with each other to organize cellular behavior and responses. This sophisticated microenvironment can be mimicked by advanced materials presenting essential biochemical and physical properties in a synergistic manner. In this work, we developed a facile fabrication method for a novel nanofibrous self-assembled peptide amphiphile (PA) and poly(ethylene glycol) (PEG) composite hydrogel system with independently tunable biochemical, mechanical, and physical cues without any chemical modification of polymer backbone or additional polymer processing techniques to create synthetic ECM analogues. This approach allows noninteracting modification of multiple niche properties (e.g., bioactive ligands, stiffness, porosity), since no covalent conjugation method was used to modify PEG monomers for incorporation of bioactivity and porosity. Combining the self-assembled PA nanofibers with a chemically cross-linked polymer network simply by facile mixing followed by photopolymerization resulted in the formation of porous bioactive hydrogel systems. The resulting porous network can be functionalized with desired bioactive signaling epitopes by simply altering the amino acid sequence of the self-assembling PA molecule. In addition, the mechanical properties of the composite system can be precisely controlled by changing the PEG concentration. Therefore, nanofibrous self-assembled PA/ PEG composite hydrogels reported in this work can provide new opportunities as versatile synthetic mimics of ECM with independently tunable biological and mechanical properties for tissue engineering and regenerative medicine applications. In addition, such systems could provide useful tools for investigation of how complex niche cues influence cellular behavior and tissue formation both in two-dimensional and three-dimensional platforms.
Microactuators toward microvalves for responsive controlled drug delivery
Sensors and Actuators B: Chemical, 2000
A responsive controlled drug release system in which the delivery of drugs is achieved by actuating miniature metal or polymeric valves has been introduced. These valves might be actuated under the control of a sensor responding to a specific biological stimulus. This approach offers better reproducibility and easier control than drug release achieved by passive diffusion out of a polymer host matrix. The metal valve systems, which are irreversible, consist of thin suspended non-porous layers that can be electrochemically dissolved or disintegrated by water electrolysis. The reversible polymeric valve systems, also called 'artificial muscle', are prepared from a blend of redox polymer and hydrogel that swells and shrinks either by applying a suitable bias or through a specific chemical reaction. In one of the several possible configurations for the artificial muscle valves such as the sphincter configuration, the blend is electropolymerized within an array of holes, which open and close corresponding to the shrinking and swelling of the polymer actuator. The swelling and shrinking property of the blends is characterized by video monitoring and by in situ conductivity measurements. Significantly larger magnitude of swelling and shrinking were observed for the blend than the redox polymer itself. The blend also Ž appeared smoother and more voluminous. The largest actuation was obtained for the blend consisting of polyaniline and poly 2-hydroxy-. Ž . ethylmethacrylate -poly N-vinylpyrrolidinone . The results demonstrate that it is possible to apply artificial muscle for the fabrication of microactuator valves for responsive controlled drug delivery. q 2000 Elsevier Science S.A. All rights reserved.