Nathaniel A. Lynd

Tunable, High Modulus Hydrogels Driven by Ionic Coacervation

The need for robust and responsive hydrogels in numerous pharmaceutical, biomedical, and industrial applications has motivated intense research efforts in these important polymeric materials. [ 1–6 ] The defi ning feature of hydrogels is that the vast majority of their mass consists of water, yet they still exhibit solid-like mechanical properties due to the presence of a three-dimensional network structure that, classically, is created through in situ covalent bond formation between multifunctional, reactive precursors. [ 6 , 7 ] A wide variety of chemistries have been utilized for covalent crosslinking of hydrogel-forming materials, e.g. free radical polymerization, Michael addition, and thiol-ene coupling, with the resulting hydrogels having good mechanical properties arising from the strong covalently bonded framework. [ 1 , 6–10 ] Limitations of the covalent approach are that the hydrogels are not re-moldable once formed, have limited responsiveness to external stimuli, and may require organic co-solvents/reagents during their formation. To overcome these limitations, hydrogels formed through non-covalent, physical associations arising from intermolecular interactions, in lieu of covalent crosslinks, have attracted signifi cant interest recently, particularly as responsive materials and injectable gels. [ 5 , 6 ] Typically, a drawback of such physically-associated hydrogels is their poor mechanical properties due to generally weak intermolecular interactions. [ 11 , 12 ] However, recent work by Gong et al. [ 13 ] and Yasuda et al . [ 14 ] on double network gels and Wang et al . [ 15 ] on the development of “aquamaterials” has demonstrated that signifi cant improvement in hydrogel mechanical properties is possible through careful design of the intermolecular interactions and length-scales between crosslinks or physical associations. In addressing new strategies to yield high performance, physically associated hydrogels, the role of dynamic materials formed via electrostatic interactions serves as a powerful model. While block copolyelectrolytes are widely used in the construction of hydrogel materials, the majority of these systems are based on block copolymers where the ionic blocks serve as the water soluble component and neutral, hydrophobic blocks

Linear versus Dendritic Molecular Binders for Hydrogel Network Formation with Clay Nanosheets: Studies with ABA Triblock Copolyethers Carrying Guanidinium Ion Pendants

ABA-triblock copolyethers 1a-1c as linear polymeric binders, in combination with clay nanosheets (CNSs), afford high-water-content moldable supramolecular hydrogels with excellent mechanical properties by constructing a well-developed crosslinked network in water. The linear binders carry in their terminal A blocks guanidinium ion (Gu(+)) pendants for adhesion to the CNS surface, while their central B block comprises poly(ethylene oxide) (PEO) that serves as a flexible linker for adhered CNSs. Although previously reported dendritic binder 2 requires multistep synthesis and purification, the linear binders can be obtained in sizable quantities from readily available starting materials by controlled polymerization. Together with dendritic reference 2, the modular nature of compounds 1a-1c with different numbers of Gu(+) pendants and PEO linker lengths allowed for investigating how their structural parameters affect the gel network formation and hydrogel properties. The newly obtained hydrogels are mechanically as tough as that with 2, although the hydrogelation takes place more slowly. Irrespective of which binder is used, the supramolecular gel network has a shape memory feature upon drying followed by rewetting, and the gelling water can be freely replaced with ionic liquids and organic fluids, affording novel clay-reinforced iono- and organogels, respectively.

A general approach to controlling the surface composition of poly(ethylene oxide)-based block copolymers for antifouling coatings.

To control the surface properties of a polystyrene-block-poly(ethylene oxide) diblock copolymer, perfluorinated chemical moieties were specifically incorporated into the block copolymer backbone. A polystyrene-block-poly[(ethylene oxide)-stat-(allyl glycidyl ether)] [PS-b-P(EO-stat-AGE)] statistical diblock terpolymer was synthesized with varying incorporations of allyl glycidyl ether (AGE) in the poly(ethylene oxide) block from 0 to 17 mol %. The pendant alkenes of the AGE repeat units were subsequently functionalized by thiol-ene chemistry with 1H,1H,2H,2H-perfluorooctanethiol, yielding fluorocarbon-functionalized AGE (fAGE) repeat units. (1)H NMR spectroscopy and size-exclusion chromatography indicated well-defined structures with complete functionalization of the pendant alkenes. The surfaces of the polymer films were characterized after spray coating by X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure spectroscopy (NEXAFS), showing that the P(EO-stat-fAGE) block starts to compete with polystyrene to populate the surface after only 1 mol % incorporation of fAGE. Increasing the incorporation of fAGE led to an increased amount of perfluorocarbons on the surface and a decrease in the concentration of PS. At a fAGE incorporation of 8 mol %, PS was not detected at the surface, as measured by NEXAFS spectroscopy. Water contact angles measured by the captive-air-bubble technique showed the underwater surfaces to be dynamic, with advancing and receding contact angles varying by >20°. Protein adsorption studies demonstrated that the fluorinated surfaces effectively prevent nonspecific binding of proteins relative to an unmodified PS-b-PEO diblock copolymer. In biological systems, settlement of spores of the green macroalga Ulva was significantly lower for the fAGE-incorporated polymers compared to the unmodified diblock and a polydimethylsiloxane elastomer standard. Furthermore, the attachment strength of sporelings (young plants) of Ulva was also reduced for the fAGE-containing polymers, affirming their potential as fouling-release coatings.

Synthetic Aptamer-Polymer Hybrid Constructs for Programmed Drug Delivery into Specific Target Cells

Viruses have evolved specialized mechanisms to efficiently transport nucleic acids and other biomolecules into specific host cells. They achieve this by performing a coordinated series of complex functions, resulting in delivery that is far more efficient than existing synthetic delivery mechanisms. Inspired by these natural systems, we describe a process for synthesizing chemically defined molecular constructs that likewise achieve targeted delivery through a series of coordinated functions. We employ an efficient “click chemistry” technique to synthesize aptamer-polymer hybrids (APHs), coupling cell-targeting aptamers to block copolymers that secure a therapeutic payload in an inactive state. Upon recognizing the targeted cell-surface marker, the APH enters the host cell via endocytosis, at which point the payload is triggered to be released into the cytoplasm. After visualizing this process with coumarin dye, we demonstrate targeted killing of tumor cells with doxorubicin. Importantly, this process can be generalized to yield APHs that specifically target different surface markers.

Ketene Functionalized Polyethylene: Control of Cross-Link Density and Material Properties

The functionalization and cross-linking of polyethylene is synthetically challenging, commonly relying on highly optimized radical based postpolymerization strategies. To address these difficulties, a norbornene monomer containing Meldrums acid is shown to be effectively copolymerized with polyethylene using a nickel α-iminocarbaxamidato complex, providing high-melting, semicrystalline polymers with a tunable incorporation of the functional comonomer. Upon heating the copolymer to common polyethylene processing temperatures, the thermolysis of Meldrums acid to ketene provides the desired reactive group. This simple and versatile methodology does not require small molecule radical sources or catalysts, and the dimerization of the in situ generated ketenes is shown to provide tunable cross-linking densities in polyethylene. Subsequent rheological and tensile experiments illustrate the ability to tune cross-linked polyethylene properties by comonomer incorporation and elucidate valuable structure/property relationships in these materials. This study illustrates the power of well-defined and synthetically accessible functional groups in polyolefin synthesis and functionalization.

pH-triggered self-assembly of biocompatible histamine-functionalized triblock copolymers

Histamine functionalized poly(allyl glycidyl ether)-b-poly(ethylene glycol)-b-poly(allyl glycidyl ether) (PAGE-PEO-PAGE) triblock copolymers represent a new class of physically cross-linked, pH-responsive hydrogels with significant potential for biomedical applications. These telechelic triblock copolymers exhibited abrupt and reversible hydrogelation above pH 7.0 due to a hudrophilic/hydrophobic transition of the histamine units to form a network of hydrophobic domains bridged by a hydrophilic PEO matrix. These hydrophobic domains displayed improved ordering upon increasing pH and self-assembled into a body centered cubic lattice at pH 8.0, while at lower concentrations formed well-defined micelles. Significantly, all materials were found to be non-toxic when evaluated on three different cell lines and suggests a range of medical and biomedical applications.

Synthesis of thermally stable Au-core/Pt-shell nanoparticles and their segregation behavior in diblock copolymer mixtures

We report a facile strategy for the preparation of sub-5 nm gold/platinum (Au-Pt) nanoparticles which are thermally stabilized by a crosslinked polymer shell. Diblock copolymer (PS-b-PI-SH) ligands on the Au nanoparticles were used to crosslink the vinyl functionalities on PIviahydrosilylation with 1,1,3,3-tetramethyldisiloxane in the presence of a platinum catalyst. The Pt catalyst was reduced on the Au nanoparticles during the hydrosilylation reaction resulting in the formation of a Pt-shell on the Au nanoparticle. The hydrosilylation reaction on the Au nanoparticles as well as their positioning in films of a poly(styrene-b-2-vinylpyridine) (PS-b-P2VP) block copolymer were thoroughly characterized by X-ray diffraction (XRD), high-resolution transmission electron microscopy (HR-TEM), UV-VIS spectroscopy, and X-ray photoelectron spectroscopy (XPS). Variables such as number of vinyl groups on PS-b-PI-SH ligands, the areal density of these ligands on the Au nanoparticle as well as the concentrations of the reactive species were varied systematically to obtain thermally stable nanoparticles. Au-Pt nanoparticles were stable in organic solvents up to 130 °C, and in polymer films at 190 °C for several days. This increased stability allowed the nanoparticles to be thermally annealed in films of PS-b-P2VP where their strong interfacial activity and localization were observed.

Small Angle Neutron Scattering Study of Complex Coacervate Micelles and Hydrogels Formed from Ionic Diblock and Triblock Copolymers

A complex coacervate is a fluid phase that results from the electrostatic interactions between two oppositely charged macromolecules. The nature of the coacervate core structure of hydrogels and micelles formed from complexation between pairs of diblock or triblock copolymers containing oppositely charged end-blocks as a function of polymer and salt concentration was investigated. Both ABA triblock copolymers of poly[(allyl glycidyl ether)-b-(ethylene oxide)-b-(allyl glycidyl ether)] and analogous poly[(allyl glycidyl ether)-b-(ethylene oxide)] diblock copolymers, which were synthesized to be nearly one-half of the symmetrical triblock copolymers, were studied. The poly(allyl glycidyl ether) blocks were functionalized with either guanidinium or sulfonate groups via postpolymerization modification. Mixing of oppositely charged block copolymers resulted in the formation of nanometer-scale coacervate domains. Small angle neutron scattering (SANS) experiments were used to investigate the size and spacing of the coacervate domains. The SANS patterns were fit using a previously vetted, detailed model consisting of polydisperse core-shell micelles with a randomly distributed sphere or body-centered cubic (BCC) structure factor. For increasing polymer concentration, the size of the coacervate domains remained constant while the spatial extent of the poly(ethylene oxide) (PEO) corona decreased. However, increasing salt concentration resulted in a decrease in both the coacervate domain size and the corona size due to a combination of the electrostatic interactions being screened and the shrinkage of the neutral PEO blocks. Additionally, for the triblock copolymers that formed BCC ordered domains, the water content in the coacervate domains was calculated to increase from approximately 16.8% to 27.5% as the polymer concentration decreased from 20 to 15 wt %.

Mussel-Inspired Anchoring of Polymer Loops That Provide Superior Surface Lubrication and Antifouling Properties

We describe robustly anchored triblock copolymers that adopt loop conformations on surfaces and endow them with unprecedented lubricating and antifouling properties. The triblocks have two end blocks with catechol-anchoring groups and a looping poly(ethylene oxide) (PEO) midblock. The loops mediate strong steric repulsion between two mica surfaces. When sheared at constant speeds of ∼2.5 μm/s, the surfaces exhibit an extremely low friction coefficient of ∼0.002-0.004 without any signs of damage up to pressures of ∼2-3 MPa that are close to most biological bearing systems. Moreover, the polymer loops enhance inhibition of cell adhesion and proliferation compared to polymers in the random coil or brush conformations. These results demonstrate that strongly anchored polymer loops are effective for high lubrication and low cell adhesion and represent a promising candidate for the development of specialized high-performance biomedical coatings.

Fluidity and water in nanoscale domains define coacervate hydrogels

Coacervate-based hydrogels, formed in aqueous solution by simple mixing of two oppositely charged ABA block copolyelectrolytes represent a new and versatile approach to the design of bio-inspired gelators. While coacervate-based hydrogels provide high tunability of a range of desirable properties, little is understood about the molecular-level makeup of the nanometer-scale domains. Small angle neutron scattering was employed to quantify the effective polymer density and water content of each domain. Further, electron paramagnetic resonance and Overhauser dynamic nuclear polarization of block-specific spin labels elucidate domain-specific, local, polymer and water dynamics. This unique combination of techniques reveals that the charged A blocks segregate into spherical domains with a radius of 8 nm, and are dispersed in a continuous matrix of water soluble, PEO B blocks. The edges of the spherical A block domains are found to be soft and diffuse, and the B block matrix exhibits higher water and polymer dynamics than the A block domains. The selective measurement of the local water and polymer dynamics shows a viscous and dense, but fluidic environment in the spherical A block domains, thus permitting the designation as a complex coacervate phase. Further, the physical properties of the analogous homopolymers mixed at equal composition to that of the triblock copolyelectrolytes leads to the conclusion that “the whole is greater than the sum of its parts”: nanometer scale complex coacervates only form when the two charged A blocks are covalently linked by a PEO midblock that serves as an intrinsic osmolyte.