Dynamic Surfaces-Degradable Polyester Networks that Resist Protein Adsorption.

We synthesized a series of novel degradable alternating copolyesters composed of diglycolic anhydride (DGA) and two epoxides, epoxymethoxytriethylene glycol (ETEG) and a photoactive crosslinking agent epoxy benzophenone (EBP). After UV crosslinking, soaking the films in a good solvent (tetrahydrofuran) removed uncrosslinked material, and the resulting film gel fractions were calculated. These network films were then degraded in buffer solutions of varying pH values. The degradation of networks with lower gel fraction (fewer crosslinks) was faster and followed first-order kinetics. In contrast, the denser network degraded slower and followed zeroth-order kinetics. The lower gel fraction networks possess a higher swelling ratio and resist bovine serum albumin (BSA) adsorption better by entropic shielding and faster degradation. In comparison, higher gel fraction networks with higher EBP mole fractions adsorb more BSA due to hydrophobic interactions and slower degradation.

Fabrication of Flexible Hydrogel Sheets Featuring Periodically Spaced Circular Holes with Continuously Adjustable Size in Real Time.

We report on the formation of stimuli-responsive structured hydrogel thin films whose pattern geometry can be adjusted on demand and tuned reversibly by varying solvent quality or by changing temperature. The hydrogel films, ∼100 nm in thickness, were prepared by depositing layers of random copolymers comprising N-isopropylacrylamide and ultraviolet (UV)-active methacryloyloxybenzophenone units onto solid substrates. A two-beam interference pattern technique was used to cross-link the selected areas of the film; any unreacted material was extracted using ethanol after UV light-assisted cross-linking. In this way, we produced nanoholes, perfectly ordered structures with a narrow size distribution, negligible tortuosity, adjustable periodicity, and a high density. The diameter of the circular holes ranged from a few micrometers down to several tens of nanometers; the hole periodicity could be adjusted readily by changing the optical period of the UV interference pattern. The holes were reversibly closed and opened by swelling/deswelling the polymer networks in the presence of ethanol and water, respectively, at various temperatures. The reversible regulation of the hole diameter can be repeated many times within a few seconds. The hydrogel sheet with circular holes periodically arranged may also be transferred onto different substrates and be employed as tunable templates for the deposition of desired substances.

Effect of Network Density in Surface-Anchored Poly(N-isopropylacrylamide) Hydrogels on Adsorption of Fibrinogen.

We describe a simple approach to generate surface-attached biocompatible hydrogels with tunable cross-link density and employ them to study the effect of gel structure on protein adsorption. Using free-radical polymerization, we synthesize a series of random copolymers comprising N-isopropylacrylamide (NIPAm) and the photoactive curing agent 4-methacryloyl-oxy-benzophenone (MABP) of mole fractions ranging from 2.5 to 10%. We deposit a thin film of the precursor copolymer (∼150 nm) on a silicon or glass substrate, which is precoated with monolayers of benzophenone-silane, then cross-link it through UV irradiation at 365 nm (dose ≈ 6-10 J/cm2) to generate surface-attached networks. A systematic investigation of the network properties such as gel fraction, cross-link density, and swelling ratio reveals that gels with higher MABP content (≥5%) produce densely cross-linked hydrophobic networks with low or no swelling in an aqueous medium. We study the adsorption of fibrinogen (Fg) on such hydrogel substrates and establish that the amount of adsorbed Fg depends on the degree of cross-linking and the swelling capacity of the networks. Specifically, although Fg adsorbs heavily on denser networks, loosely bound gels that swell in aqueous medium repel proteins. We attribute the latter behavior to entropic shielding and size-exclusion factors.

Surface-Anchored Poly(N-isopropylacrylamide) Orthogonal Gradient Networks.

We present a versatile synthetic route leading toward generating surface-attached polyacrylamide gels, in which the cross-link density varies continuously and gradually across the substrate in two orthogonal directions. We employ free radical polymerization to synthesize random copolymers comprising ~5% of photoactive methacrylyloxybenzophenone (MABP), ~5% of thermally active styrene sulfonyl azide (SSAz), and ~90% of N-isopropylacrylamide (NIPAAm) units. The presence of MABP and SSAz in the copolymer facilitates control over the cross-link density of the gel in an orthogonal manner using photoactivated and thermally activated cross-linking chemistries, respectively. Spectroscopic ellipsometry is employed to determine the degree of swelling of the gel in water and methanol as a function of position on the substrate. Network swelling varies continuously and gradually across the substrate and is high in regions of low gel fractions and low in regions of high gel fractions.

Influence of the molecular structure of surface-attached poly(N-alkyl acrylamide) coatings on the interaction of surfaces with proteins, cells and blood platelets.

Blood protein adsorption and blood platelet adhesion onto surface-attached poly(alkylacrylamide) networks that exhibit small and systematic variations in chemical composition are investigated. The polymer coatings are generated by depositing a thin layer of benzophenone-group-containing copolymer onto a solid substrate, followed by photo crosslinking and simultaneous surface-attachment. The correlation of the swelling of the obtained surface-attached networks with the adsorption of blood proteins and cellular adhesion is studied. The swollen surface-attached layers are inert to blood proteins and platelet cells. These results suggest that the hydrogel-coated materials are promising candidates for the generation of hemocompatible surfaces.