No abstract

A focused library of methacrylate terpolymers was synthesized to explore the effects of varying surface chemistry and adhesive peptide ligands on cell function. The chemical diversity of methacrylate monomers enabled construction of a library of polymers in which one can systematically vary the chemical composition to achieve a wide range of contact angle, Young's modulus, and Tg values. Furthermore, the materials were designed to allow surface immobilization of bioactive peptides. We then examined the effects of these material compositions on protein adsorption and cell attachment, proliferation, and differentiation. We observed that chemical composition of the polymers was an important determinant for NIH 3T3 cell attachment and proliferation, as well as human mesenchymal stem cell differentiation, and correlated directly with the ability of the polymers to adsorb proteins that mediate cell adhesion. Importantly, functionalization of the methacrylate terpolymer library with an adhesive GRGDS peptide normalized cellular responses. RGD-functionalized polymers uniformly exhibited robust attachment, proliferation, and differentiation irrespective of the underlying substrate chemistry. These studies provide a library-based approach to rapidly explore the biological functionality of biomaterials with a wide range of compositions, and highlights the importance of cell and protein cell adhesion in predicting their performance.

The surface properties and biocompatibility of a class of thermoplastic polyurethanes (TPUs) with applications in blood-contacting medical devices have been studied. Thin films of commercial TPUs and novel polyisobutylene (PIB)-poly(tetramethylene oxide) (PTMO) TPUs were characterized by contact angle measurements, X-ray photoelectron spectroscopy, and atomic force microscopy (AFM) imaging. PIB-PTMO TPU surfaces have significantly higher C/N ratios and lower amounts of oxygen than the theoretical bulk composition, which is attributed to surface enrichment of PIB. Greater differences in the C/N ratios were observed with the softer compositions due to their higher relative amounts of PIB. The contact angles were higher on PIB-PTMO TPUs than on commercial polyether TPUs, indicating lower surface energy. AFM imaging showed phase separation and increasing domain sizes with increasing hard segment content. The biocompatibility was investigated by quantifying the adsorption of fouling and passivating proteins, fibrinogen (Fg) and human serum albumin (HSA) respectively, onto thin TPU films spin coated onto the electrode of a quartz crystal microbalance with dissipation monitoring (QCM-D). Competitive adsorption experiments were performed with a mixture of Fg and albumin in physiological ratio followed by binding of GPIIb-IIIa, the platelet receptor ligand that selectively binds to Fg. The QCM-D results indicate similar adsorbed amounts of both Fg and HSA on PIB-PTMO TPUs and commercial TPUs. The strength of the protein interactions with the various TPU surfaces measured with AFM (colloidal probe) was similar among the various TPUs. These results suggest excellent biocompatibility of these novel PIB-PTMO TPUs, similar to that of polyether TPUs.

No abstract

It has often been observed anecdotally and implied through experimentation that acrylic emulsion paintings accumulate and entrain soils over time due to the inherent mechanical softness in artist's acrylic paint films, through the presence of hydrophilic film components, and by virtue of the ubiquitous presence of surfactant moieties on these film surfaces once they dry. In the present study, it has been this last effect that we have sought to describe more fully in terms of surfactant responsiveness to both temperature and relative humidity (RH). Surfactant hydration and dehydration under varying temperature and RH conditions affects the ultimate partitioning of the surfactant at the paint-air interface, as well as the inherent size, aggregation tendencies, and solubility of surfactant in the bulk paint materials which contain components that are highly responsive to changes in temperature and RH (e.g. polyacrylic or polymaleic anhydride-type dispersal materials). In this work, analytical techniques including three-dimensional microscopy and quartz crystal microbalance with dissipation were used to add to and reinforce current understanding of the physical and mechanical changes to acrylic paint films with temperature and RH. The migration of surfactant at the film surface was studied using desorption electrospray ionization-mass spectrometry and attenuated total reflectance Fourier transform infrared microscopy.

Regulation of smooth muscle cell adhesion, proliferation, and motility on biomaterials is critical to the performance of blood-contacting implants and vascular tissue engineering scaffolds. The goal of this study was to examine the underlying substrate-smooth muscle cell response relations, using a selection of polymers representative of an expansive library of multifunctional, tyrosine-derived polycarbonates. Three chemical components within the polymer structure were selectively varied through copolymerization: 1) the content of iodinated tyrosine to achieve X-ray visibility; 2) the content of poly(ethylene glycol) (PEG) to decrease protein adsorption and cell adhesivity; and 3) the content of desaminotyrosyl-tyrosine (DT) which regulates the rate of polymer degradation. Using quartz crystal microbalance with dissipation, we quantified differential serum protein adsorption behavior due to the chemical components DT, iodinated tyrosine, and PEG: increased PEG content within the polymer structure progressively decreased protein adsorption but the simultaneous presence of both DT and iodinated tyrosine reversed the effects of PEG. The complex interplay of these components was next tested on the adhesion, proliferation, and motility behavior cultured human aortic smooth muscle cells. The incorporation of PEG into the polymer reduced cell attachment, which was reversed in the presence of iodinated tyrosine. Further, we found that as little as 10% DT content was sufficient to negate the PEG effect in polymers containing iodinated tyrosine while in non-iodinated polymers the PEG effect on cell attachment was reversed. Cross-functional analysis of motility and proliferation revealed divergent substrate chemistry related cell response regimes. For instance, within the series of polymers containing both iodinated tyrosine and 10% of DT, increasing PEG levels lowered smooth muscle cell motility without a change in the rate of cell proliferation. In contrast, for non-iodinated tyrosine and 10% of DT, increasing PEG levels increased cell proliferation significantly while reducing cell motility. Clearly, the polycarbonate polymer library offers a sensitive platform to modulate cell adhesion, proliferation, and motility responses, which, in turn, may have implications for controlling vascular remodeling in vivo. Additionally, our data suggests unique biorelevant

Distribution of water in three classes of biomedically relevant and degradable polymers was investigated using small-angle neutron scattering. In semicrystalline polymers, such as poly(lactic acid) and poly(glycolic acid), water was found to diffuse preferentially into the noncrystalline regions. In amorphous polymers, such as poly(D,L-lactic acid) and poly(lactic-co-glycolic acid), the scattering after 7-days of incubation was attributed to water in microvoids that form following the hydrolytic degradation of the polymer. In amorphous copolymers containing hydrophobic segments (desaminotyrosyl-tyrosine ethyl ester) and hydrophilic blocks (poly(ethylene glycol) PEG), a sequence of distinct regimes of hydration were observed: homogeneous distribution (~ 10 Å length scales) at <13 wt% PEG (~ 1 water per EG), clusters of hydrated domains (~50 Å radius) separated at 24 wt% PEG (1 to 2 water per EG), uniformly distributed hydrated domains at 41 wt% PEG (~ 4 water per EG), and phase inversion at > 50 wt% PEG ( > 6 water per EG ). Increasing PEG content increased the number of these domains with only a small decrease in distance between the domains. These discrete domains appeared to coalesce to form submicron droplets at ~60 °C, above the melting temperature of crystalline PEG. Significance of such observations on the evolution of μm size channels that form during hydrolytic erosion is discussed.

Increase in modulus upon hydration in copolymers of desaminotyrosyl-tyrosine ethyl ester (DTE) and poly(ethylene glycol) (PEG) with iodinated tyrosines, poly(I2DTE-co-PEG carbonate)s, was investigated by varying the fraction and the molecular weight of the hydrophilic PEG component. Water, as expected, acts as plasticizer in polymer with PEG content < 15 wt% and > 30 wt%. But, water has the opposite effect in iodinated polymers with moderate PEG contents, between 15 to 20 wt%: it enhances the Young's modulus. The strength and modulus of hydrated poly(I2DTE-co-15%PEG2K carbonate)s increased by as much as fifteen fold upon hydration. While the decrease in the mechanical properties in most polymeric materials with diluents such water is due to the solvent-induced swelling, the increase in strength and modulus that is observed is most likely due to the reinforcing effect of the increased cross-linking efficiency of the hydrated PEG domains in the iodinated polymer.