Ryan Toomey

Functional Polymer Brushes in Aqueous Media from Self-Assembled and Surface-Initiated Polymers

This review focuses on the behavior of single-component, water-soluble neutral and charged brushes. Selected examples illustrate how solvation effects, hydrophobic interactions, and electrostatic interactions create complex behaviors not easily captured in mean-field treatments. In particular, we distinguish between two classes of polymer brushes: those that can be described classically within the context of generalized van der Waals potentials and those that can be described by model-dependent potentials arising from specific interactions. In classical systems, only a few global parameters are needed to predict behavior. Nonclassical systems, in contrast, necessitate several local details, which do not necessarily lead to universal scaling laws. Although these nonclassical interactions present unique opportunities for engineering functional surfaces, they also present new challenges for designing well-defined systems with precise control over distributions in the degree of polymerization and tethering density.

Swelling-induced instabilities in microscale, surface-confined poly(N-isopropylacryamide) hydrogels

A hydrogel is a three-dimensional hyperelastic polymer network that swells to a specific volume upon exposure to a penetrating solvent. If mechanical constraints interfere with the swelling process, anisotropic compressive stresses are generated, which may manifest in local or global instabilities. Herein, we employ confocal microscopy for the in situ, three-dimensional study of micron-scale hydrogels that are pinned to a solid substrate. Depending on the initial geometry of the hydrogel, four general modes of swelling-induced deformation were found: lateral differential swelling, local sinusoidal edge buckling, bulk sinusoidal buckling, and surface creasing. The transition between local edge buckling and bulk buckling is consistent with linear elastic theory; however, linear theory cannot be used to predict many details of the swollen structures. Whereas global buckling has a well-defined wavelength that depends on height of the hydrogel structure, edge buckling appears to be independent of height and depends on sample history. Moreover, edge buckling can appear in globally buckled structures, suggesting two different mechanisms for the two instabilities.

Surface instabilities in ultrathin, cross-linked poly(N-isopropylacrylamide) coatings.

Near-the-surface instabilities with a cusplike morphology were observed in ultrathin photo-cross-linked poly(N-isopropylacrylamide) coatings upon swelling in water. The characteristic wavelength of the instability was approximately 25 times the dry thickness and scaled linearly with coating thickness between 30 and 1200 nm. Above 1200 nm, slippage of the coating along the confining substrate led to reticulated patterns with a much larger wavelength. To help interpret the origin of the instability, the coatings were also exposed to a solvent slightly worse than water (acetone) and a solvent slightly better than water (isopropanol). In all cases, the characteristic wavelength scaled linearly with respect to the swelling induced by each solvent. Both water and isopropanol produced well-defined cusps or folds in the gel surface, while acetone produced semiordered blisters that grew into one another. The features produced in acetone may be a consequence of swelling being close to the threshold value for the loss of planar stability. Through the use of a first-order linear perturbation of the Flory-Rehner model, it is shown that the emergence of a characteristic wavelength is consistent with an inhomogeneous distribution of solvent that results from diffusion of solvent into a dry coating.

The effect of the Hofmeister series on the deswelling isotherms of poly(N-isopropylacrylamide) and poly(N,N-diethylacrylamide)

The influence of Na2SO4, NaCl, NaBr, and NaI was studied on the deswelling isotherms of thin films of photo-crosslinked poly(N-isopropylacrylamide) and poly(N,N-diethylacrylamide) to help elucidate the mechanisms by which ions of the Hofmeister series affect the solubility of neutral, amide-based polymers. The films were characterized with both ellipsometry and FTIR to determine both water content and the frequency of the CO, N–H, and CH3 vibrations associated with the polymers. When compared at the same water content, the frequency of the N–H bend in poly(NIPAAm) red-shifts in the order I− > Cl− > Br− > SO42−. The red-shift is consistent with disrupted hydrogen bonding of the N–H moiety due to an ion–dipole attraction. The CO stretch on the other hand is insensitive to the ion, suggesting that the ion pairs primarily with the partially positive end of the HN–CO dipole. For poly(DEAAm), which lacks an N–H moiety, the CO stretch is now sensitive to the ion, with the trend following the order of the ion in the Hofmeister series. Both of these findings signify that I− > Cl− > Br− > SO42− with respect to the strength of the ion–dipole interaction. Moreover, the ion–dipole interaction is stronger in poly(NIPAAm) than poly(DEAAm), suggesting that the specificity of the Hofmeister ions arises from the effect of vicinal groups on the amide dipole.

Continuous and discontinuous volume-phase transitions in surface-tethered, photo-crosslinked poly(N-isopropylacrylamide) networks

The water–polymer demixing behavior of surface-tethered poly(N-isopropylacrylamide) networks copolymerized with x mol% of photo-crosslinkable methacryloyloxybenzophenone (MaBP) (x = 1, 3, 5, 10%) was characterized with neutron reflection and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. Neutron reflection revealed that water is expelled discontinuously at low crosslink densities and continuously at high crosslink densities. The demarcation between the two behaviors occurred roughly at the critical point as measured by cloud point experiments. The neutron reflection experiments further revealed that the discontinuous concentration jump at low crosslink densities takes place in the presence of significant amounts of water and that water is not completely expelled in the process, with 2–3 water molecules remaining per polymer segment after the collapse of the network, independent of crosslink density. Parallel measurements with ATR-FTIR confirm that the transition is driven by dehydration of the isopropyl groups, with water remaining confined between the amide groups even at temperatures well above the demixing temperature. The internal water, however, is readily exchanged with deuterium oxide at temperatures up to 100 °C. This exchange points to the absence of a hydrophobic skin or physical barrier that would prevent water from completely leaving the film above the demixing temperature.

Shape-changing hydrogel surfaces trigger rapid release of patterned tissue modules.

The formation and assembly of diverse tissue building blocks is considered a promising bottom-up approach for the construction of complex three-dimensional tissues. Patterned shape-changing materials were investigated as an innovative method to form and harvest free-standing tissue modules with preserved spatial organization and cell-cell connections. Arrays of micro-scale surface-attached hydrogels made of a thermoresponsive polymer were used as cell culture supports to fabricate tissue modules of defined geometric shape. Upon stimulation, these hydrogels swelled anisotropically, resulting in significant expansion of the culture surface and subsequent expulsion of the intact tissue modules. By varying the network crosslink density, the surface strain was modulated and a strain threshold for tissue module release was identified. This mechanical mechanism for rapid tissue module harvest was found to require inter- and intra-cellular tension. These results suggest that the cell-matrix adhesions are disrupted by the incompatibility of surface expansion with tissue module cohesion and stiffness, thus providing a novel method of forming and harvesting tissue building blocks by a mechanism independent of the thermal stimulus that induces the biomaterial shape change.

Poly(N-isopropylacrylamide) cross-linked coatings with phototunable swelling.

A series of terpolymers were synthesized comprising the following monomers: N-isopropylacrylamide (NIPAAm), a stimuli-responsive structural unit that swells and collapses in response to temperature; methacryloxybenzophenone (MaBP), a photo-cross-linking unit that is activated at a wavelength of 365 nm; and phenacyl methacrylate (PHEm), a photolabile protected carboxyl group that can be deprotected at a wavelength of 254 nm. It is shown that the terpolymers can be photo-cross-linked at long UV wavelength light (λ = 365 nm) to establish surface-attached, cross-linked coatings and subsequently photochemically cleaved at short UV wavelength light (λ = 254 nm), which is found to be consistent with first-order kinetics. The photocleavage reaction produces free carboxylic groups, which can be used to locally tune the swelling characteristics and transition temperature of the coating, which depends on both the irradiation exposure and the overall PHEm content. For instance, for a terpolymer with 7.1 mol % PHEm, the transition temperature between the swollen and collapsed states increased from 20 to 50 °C at a pH of 8.5 with an exposure dose of 0.52 J/cm(2) at 254 nm. Finally, photocleavage can be used to create chemically patterned regions to provide a basis by which to conjugate cationic markers, proteins, or nanoparticles to the terpolymer coating.

Protein-surface interactions on stimuli-responsive polymeric biomaterials.

Responsive surfaces: a review of the dependence of protein adsorption on the reversible volume phase transition in stimuli-responsive polymers. Specifically addressed are a widely studied subset: thermoresponsive polymers. Findings are also generalizable to other materials which undergo a similarly reversible volume phase transition. As of 2015, over 100,000 articles have been published on stimuli-responsive polymers and many more on protein-biomaterial interactions. Significantly, fewer than 100 of these have focused specifically on protein interactions with stimuli-responsive polymers. These report a clear trend of increased protein adsorption in the collapsed state compared to the swollen state. This control over protein interactions makes stimuli-responsive polymers highly useful in biomedical applications such as wound repair scaffolds, on-demand drug delivery, and antifouling surfaces. Outstanding questions are whether the protein adsorption is reversible with the volume phase transition and whether there is a time-dependence. A clear understanding of protein interactions with stimuli-responsive polymers will advance theoretical models, experimental results, and biomedical applications.

Thermoresponsive PNIPAM Coatings on Nanostructured Gratings for Cell Alignment and Release

Thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) has been widely used as a surface coating to thermally control the detachment of adsorbed cells without the need for extreme stimuli such as enzyme treatment. Recently, the use of 2D and 3D scaffolds in controlling cell positioning, growth, spreading, and migration has been of a great interest in tissue engineering and cell biology. Here, we use a PNIPAM polymer surface coating atop a nanostructured linear diffraction grating to controllably change the surface topography of 2D linear structures using temperature stimuli. Neutron reflectometry and surface diffraction are utilized to examine the conformity of the polymer coating to the grating surface, its hydration profile, and its evolution in response to temperature variations. The results show that, in the collapsed state, the PNIPAM coating conforms to the grating structures and retains a uniform hydration of 63%. In the swollen state, the polymer expands beyond the grating channels and absorbs up to 87% water. Such properties are particularly desirable for 2D cell growth scaffolds with a built-in nonextreme tissue-release mechanism. Indeed, the current system demonstrates advanced performance in the effective alignment of cultured fibroblast cells and the easy release of the cells upon temperature change.

Influence of lipid membrane rigidity on properties of supporting polymer.

Temperature-sensitive hydrogel polymers are utilized as responsive layers in various applications. Although the polymers native characteristics have been studied extensively, details concerning its properties during interaction with biorelated structures are lacking. This work investigates the interaction between a thermoresponsive polymer cushion and different lipid membrane capping layers probed by neutron reflectometry. N-isopropylacrylamide copolymerized with methacroylbenzophenone first supported a lipid bilayer composed of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) and subsequently 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). The polymer-membrane systems were investigated above and below the polymer transition temperature (37 and 25°C). Although the same cushion supported each lipid membrane, the polymer hydration profile and thickness were markedly different for DPPE and DPPC systems. Because DPPE and DPPC have different bending rigidities, these results establish that the polymer-membrane interaction is critically mediated by the mechanics of the membrane, providing better insight into cell-hydrogel interactions.