PEG Networks Research Articles

Tunable Networks from Thiolene Chemistry for Lithium Ion Conduction.

End-functionalized poly(ethylene glycol) (PEG) and polydimethylsiloxane (PDMS) were cross-linked by a thiolene reaction with a tetra-functional thiol to create robust, tunable networks. These networks were loaded with increasing amounts of lithium bis(trifluoromethane sulfonyl imide) (LiTFSI), and their ion conductivity was measured. A wide range of salt loading was achieved, allowing the investigation of both salt-in-polymer and polymer-in-salt regimes. Thermal, mechanical, and ion conductivity properties of LiTFSI-loaded PEG and PEG-PDMS networks were measured. Even at high salt loadings, both networks maintained rubber-like characteristics, which were stable over a range of temperatures (30-90 °C). The PEG network with the highest salt loading showed the greatest ion conductivity, 6.7 × 10-4 S cm-1 at 30 °C, as measured by impedance spectroscopy. This system provides a route to optimize lithium ion conduction and mechanical properties.

Targeted surface nanocomplexity: two-dimensional control over the composition, physical properties and anti-biofouling performance of hyperbranched fluoropolymer–poly(ethylene glycol) amphiphilic crosslinked networks

A two-dimensional array of amphiphilic crosslinked networks was prepared by systematic alteration of both the composition of hyperbranched fluoropolymers (HBFPs) and the relative stoichiometries upon crosslinking with poly(ethylene glycol) (PEG). Results of physicochemical, mechanical, surface and biofouling assessment are described in full. The materials were designed to present complex surface topographies, morphologies, and chemical features over nano- and microscopic dimensions to explicitly inhibit microorganism settlement and adhesion. A multi-dimensional, tunable matrix was generated to understand and optimize the composition–structure–property relationships. The thermal properties of the crosslinked networks were analyzed by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), where the onset of thermal degradation, overall thermal stability and phase transition temperatures could be controlled based on the formulation. Investigation of the mechanical properties of the coatings in the water-swollen state found that the Young's modulus, ranging between 10.0 and 121 MPa, was dependent on both the wt% of PEG crosslinker and chemical composition of the HBFP. This result, on average, gives Young's moduli an order of magnitude larger than that previously reported for HBFP–PEG networks. Use of atomic force microscopy (AFM) provided insight into the nanoscale topography of the networks. Interestingly, it was observed that for all networks, surface roughness increased with water swelling going from an average of 115 ± 49 nm (dry) to 214 ± 106 nm (swelled) RMS roughness. Probing the surface chemistry by optical tensiometry revealed an increase in the static water contact angle by as much as 40° after water swelling. These two findings display a counter-intuitive increase of the surface hydrophobicity. Secondary ion mass spectrometry (SIMS) confirmed migration of hydrophobic fluorocarbon units to the surface by quantifying a 24% increase in fluorine species ejected from a dry versus water-swollen surface. Selected formulations of HBFP–PEG that demonstrated complex surface features and an overall high mechanical strength were tested in biological assays and all surfaces (3 formulations × 12 replicates) completely resisted the settlement of barnacle cyprids (Balanus amphitrite). Diatoms (Navicula incerta) were two- to three-times more easily removed from the HBFP–PEG surfaces compared to a homogeneous polydimethylsiloxane elastomer (PDMSe) standard surface. In contrast, algal spores (Ulva linza) were able to colonize the surfaces and were more difficult to remove in comparison to the PDMSe standard, pointing to the challenges associated with the development of a single material that is capable of broad anti-biofouling performance.

Poly(p-dioxanone)–poly(ethylene glycol) network: synthesis, characterization, and its shape memory effect

Multi-shape polymers have recently attracted growing interest on account of their ability to switch between multiple shapes in a predetermined way. In this work, thermally induced shape-memory PPDO–PEG networks with well-defined architecture have been designed and prepared by coupling hydroxyl-telechelic three-arm star-shaped PPDO and PEG diol precursors with HDI in 1,2-dichloroethane. The molecular weight and the feed ratio of the two precursors affected the gel content and the cross-link density of the network. The DSC analysis indicated that increasing the content of a precursor, or its molecular weight, was helpful in enhancing the crystallization degree of its own domains. The testing of dual-shape and triple-shape effects of networks showed that composition and cross-link density played an important role. As a typical sample, PPDO(9k)65–PEG(6k)35 exhibits a triple-shape effect, which possesses two separate and apparent melting endothermic peaks for the PPDO and PEG segments respectively.

Currency Networks, Bilateral Exchange Rate Volatility and the Role of the US Dollar

We investigate monthly bilateral exchange rate volatility for a large sample of currency pairs over the period 1999–2006. Pegs (particularly to the US dollar) and managed floats tend to have lower volatility than independent floats. A deeper investigation shows that the peg effect operates almost entirely through currency networks (i.e. where two currencies are pegged to the same anchor currency), and the lower volatility of US dollar pegs reflects the size of the US dollar network. Managed floats show clear evidence of tracking the US dollar, further increasing the effective size of the US dollar network. Inflation undermines the currency-stabilizing effect of peg networks. Currencies in smaller peg networks have higher unweighted but not trade-weighted exchange rate volatility, which is consistent with anchors being chosen to minimize trade-weighted volatility. The size of the effective US dollar network revealed here is a plausible explanation of the rarity of basket pegs. Volatility also reflects a range of structural factors such as country size, level of development, population density, inflation differentials and business cycle asymmetry.

Influence of glycosaminoglycan identity on vocal fold fibroblast behavior

Poly(ethylene glycol) (PEG) hydrogels have recently begun to be studied for the treatment of scarred vocal fold lamina propria due, in part, to their tunable mechanical properties, resistance to fibroblast-mediated contraction, and ability to be polymerized in situ. However, pure PEG gels lack intrinsic biochemical signals to guide cell behavior and generally fail to mimic the frequency-dependent viscoelastic response critical to normal superficial lamina propria function. Recent results suggest that incorporation of viscoelastic bioactive substances, such as glycosaminoglycans (GAGs), into PEG networks may allow these gels to more closely approach the mechanical responses of normal vocal fold lamina propria while also stimulating desired vocal fold fibroblast behaviors. Although a number of vocal fold studies have examined the influence of hyaluronan (HA) on implant mechanics and vocal fold fibroblast responses, the effects of other GAG types have been relatively unexplored. This is significant, since recent studies have suggested that chondroitin sulfate C (CSC) and heparan sulfate (HS) are substantially altered in scarred lamina propria. The present study was therefore designed to evaluate the effects of CSC and HS incorporation on the mechanical response of PEG gels and vocal fold fibroblast behavior relative to HA. As with PEG–HA, the viscoelasticity of PEG–CSC and PEG–HS gels more closely approached that of the normal vocal fold lamina propria than pure PEG hydrogels. In addition, collagen I deposition and fibronectin production were significantly higher in CSC than in HA gels, and levels of the myofibroblast marker smooth muscle α-actin (SM α-actin) were greater in CSC and HS gels than in HA gels. Since collagen I, fibronectin, and SM α-actin are generally elevated in scarred lamina propria these results suggest that CSC and HS may be undesirable for vocal fold implants relative to HA. Investigation of various signaling intermediates indicated that alterations in NFκB-p50, NFκB-p65, or pERK1/2 levels may underlie the observed differences among the PEG–GAG gels.

Sliding-Graft Interpenetrating Polymer Networks from Simultaneous “Click Chemistry” and Atom Transfer Radical Polymerization

In this work, a kind of semi-interpenetrating polymer network (s-IPN) with unique molecular structures, poly(ethylene glycol) (PEG) network with movable sliding-grafted poly(2-hydroxyethyl methacrylate) (PHEMA) (s-IPN-PEG/α-CD-sg- PHEMA), were first reported. s-IPN-PEG/α-CD-sg-PHEMAs were prepared by simultaneous “click chemistry” and atom transfer radical polymerization (ATRP) of a mixture of poly(ethylene glycol)-diazide/bromobutyryloxy α-cyclodextrin inclusion complex (N3-PEG-N3/(α-CD-BIBB)m), tetrakis(2-propynyloxymethyl) methane (TMOP), CuBr, pentamethyldiethylenetriamine (PMDETA), HEMA and DMF. Attributable to the controlled characters of ATRP and the quantitative yields of “click chemistry”, the prepared s-IPN-PEG/α-CD-sg-PHEMAs have the well-defined PEG networks, as well as uniform and tunable sliding-grafted PHEMA chains. The length of sliding-grafted PHEMA of the s-IPN-PEG/α-CD-sg-PHEMA can be regulated by changing polymerization times. The molecular structures, and physical and thermal properti...

Morphology of Photopolymerized End-Linked Poly(ethylene glycol) Hydrogels by Small-Angle X-ray Scattering

Due to the biocompatibility of poly(ethylene glycol) (PEG), PEG-based hydrogels have attracted considerable interest for use as biomaterials in tissue engineering applications. In this work, we show that PEG-based hydrogels prepared by photopolymerization of PEG macromonomers functionalized with either acrylate or acrylamide end-groups generate networks with crosslink junctions of high functionality. Although the crosslink functionality is not well controlled, the resultant networks are sufficiently well ordered to generate a distinct correlation peak in the small angle x-ray scattering (SAXS) related to the distance between crosslink junctions within the PEG network. The crosslink spacing is a useful probe of the PEG chain conformation within the hydrogel and ranges from approximately 6 to 16 nm, dependent upon both the volume fraction of polymer and the molecular weight of the PEG macromonomers. The presence of a peak in the scattering of photopolymerized PEG networks is also correlated with an enhanced compressive modulus in comparison to PEG networks reported in the literature with much lower crosslink functionality that exhibit no scattering peak. This comparison demonstrates that the method used to link together PEG macromonomers has a critical impact on both the nanoscale structure and the macroscopic properties of the resultant hydrogel network.

Screening for 3D Environments That Support Human Mesenchymal Stem Cell Viability Using Hydrogel Arrays

In this study we generated 3D poly(ethylene glycol) (PEG) hydrogel arrays to screen for the individual and combinatorial effects of extracellular matrix (ECM) degradability, cell adhesion ligand type, and cell adhesion ligand density on human mesenchymal stem cell (hMSC) viability. In particular, we explored the influence of two well-characterized ECM-derived cell adhesion ligands: the fibronectin-derived Arg-Gly-Asp-Ser-Pro (RGDSP) sequence, and the laminin-derived Ile-Lys-Val-Ala-Val (IKVAV) sequence. PEG network degradation, the RGDSP ligand, and the IKVAV ligand each individually increased hMSC viability in a dose-dependent manner. The RGDSP ligand also improved hMSC viability in a dose-dependent manner in degradable PEG hydrogels, while the effect of IKVAV was less pronounced in degradable hydrogels. Combinations of RGDSP and IKVAV promoted high viability of hMSCs in nondegradable PEG networks, while the combined effects of the ligands were not significant in degradable PEG hydrogels. Although hMSC spreading was not commonly observed within PEG hydrogels, we qualitatively observed hMSC spreading after 5 days only in degradable PEG hydrogels prepared with 2.5 mM of both RGDSP and IKVAV. These results suggest that the enhanced throughput approach described herein can be used to rapidly study the influence of a broad range of ECM parameters, as well as their combinations, on stem cell behavior.

Decorin moieties tethered into PEG networks induce chondrogenesis of human mesenchymal stem cells

A versatile approach to fabricate PEG-peptide copolymer gels was utilized to design niches to promote chondrogenic differentiation of human mesenchymal stem cells (hMSCs). The sequences RGD and KLER were chosen as motifs to modify PEG gels through a thiol-acrylate polymerization. The KLER sequence, a binding site from decorin protein, is known to bind strongly to collagen type II and is responsible for matrix organization, while RGD promotes general survival of encapsulated cells. hMSCs were encapsulated at 2 x 10(6) cells/mL into 10 wt % PEG gels with 1 mM CRGDSG in the presence or absence of 5 mM CKLERG. A scrambled sequence served as a control. The gels were cultured in control and chondrogenic media, containing 5 ng/mL TGFbeta(1) over a 6-week period. Cell/gel constructs were analyzed at various time points for glycosaminoglycan (GAG) content, type II collagen deposition, immunostaining, and gene analysis. After 14 days in chondrogenic cultures, cells in RGDS and KLER functionalized gels produced 2.5 times as much GAG/cell as those in gels containing only RGD. By day 28, hMSCs within the chondrogenic KLER gels produced 27-fold higher hydroxyproline than that of day 0, whereas cells in chondrogenic culture with RGDS alone produced twofold of initial. Immunostained images indicated that col II was more predominant in the KLER-derivatized gels than others, and enhanced chondrogenic differentiation in KLER containing gels was further supported by RT-PCR analysis of type II collagen and aggrecan expression. Collectively, these results demonstrate how incorporation of matrix-binding peptide interacts with hMSCs inducing chondrogenic differentiation and cartilage-specific ECM deposition.

Metal‐chelating affinity hydrogels for sustained protein release

Affinity hydrogels based on poly(ethylene glycol) diacrylate and a metal-ion-chelating ligand, glycidyl methacrylate-iminodiacetic acid, have been developed to systematically decrease protein release rates from hydrophilic tissue engineering scaffolds formed in situ. In the current work, tunable and sustained release of a model protein, hexa-histidine tagged green fluorescence protein (hisGFP), is accomplished by judiciously increasing ligand:protein ratio or replacing low-affinity nickel ions with high-affinity copper ions. Agreement between theoretical predictions of a reaction-diffusion model and experimental measurements confirm metal- ion-mediated sustained protein release from these affinity hydrogels is governed by equilibrium protein-ligand binding affinity (dissociation constant, Kd) as well as protein-ligand dissociation kinetics (protein debinding rate constant, k off). The former dictates the release rate in the early period of protein release while the latter determines the long-term sustained release effect. While metal-ion affinity binding has been widely used for various purposes including protein purification and surface patterning, this is the first report describing its application in systematically controlling protein release from hydrophilic PEG networks suitable for cell encapsulation. By using ligands with proper binding kinetic constants (Kd and k off), localized protein delivery can be sustained over clinically relevant timescales while maintaining a favorable environment for cell encapsulation and viability.

Protein Adhesion on Silicon-Supported Hyperbranched Poly(ethylene glycol) and Poly(allylamine) Thin Films

Hyperbranching poly(allylamine) (PAAm) and poly(ethylene glycol) (PEG) on silicon and its effect on protein adhesion was investigated. Hyperbranching involves sequential grafting of polymers on a surface with one of the components having multiple reactive sites. In this research, PAAm provided multiple amines for grafting PEG diacrylate. Current methodologies for generating PEG surfaces include PEG-silane monolayers or polymerized PEG networks. Hyperbranching combines the nanoscale thickness of monolayers with the surface coverage afforded by polymerization. A multistep approach was used to generate the silicon-supported hyperbranched polymers. The silicon wafer surface was initially modified with a vinyl silane followed by oxidation of the terminal vinyl group to present an acid function. Carbodiimide activation of the surface carboxyl group allowed for coupling to PAAm amines to form the first polymer layer. The polymers were hyperbranched by grafting alternating PEG and PAAm layers to the surface using Michael addition chemistry. The alternating polymers were grafted up to six total layers. The substrates remained hydrophilic after each modification. Static contact angles for PAAm (32-44 degrees) and PEG (33-37 degrees) were characteristic of the corresponding individual polymer (30-50 degrees for allylamine, 34-42 degrees for PEG). Roughness values varied from approximately 1 to 8 nm, but had no apparent affect on protein adhesion. Modifications terminating with a PEG layer reduced bovine serum albumin adhesion to the surface by approximately 80% as determined by ELISA and radiolabel binding studies. The hyperbranched PAAm and PEG surfaces described in this paper are nanometer-scale, multilayer films capable of reducing protein adhesion.

Controllable erosion time and profile in poly(ethylene glycol) hydrogels by supramolecular structure of hydrolyzable polyrotaxane.

A series of poly(ethylene glycol) (PEG) hydrogels cross-linked by a hydrolyzable polyrotaxane was prepared and the hydrolytic erosion behavior was characterized. The hydrolyzable polyrotaxane consisting of many alpha-cyclodextrins (alpha-CDs) and a PEG chain capped with bulky end groups via ester linkages was used as a cross-linker in the PEG hydrogels, where alpha-CDs in the polyrotaxane were linked with another PEG chains to form hydrophilic PEG networks. From the result of the erosion study, the time to reach complete gel erosion was found to be prolonged by decreasing the polyrotaxane content and increasing the PEG/alpha-CD ratio. The PEG/alpha-CD ratio, indicating the number of PEG chains linked with one alpha-CD molecule, is considered to make the environment of the polyrotaxane more aqueous and lead to the hydrolysis of ester linkages in the polyrotaxane. However, the higher PEG/alpha-CD ratio prolonged the time of the hydrogel erosion. These results indicate the enhanced stability of ester hydrolysis in the hydrogels with highly water swollen state. Such an anomalous phenomenon may be due to the structural characteristic of the polyrotaxane: ester linkages may be included within the cavity of alpha-CDs, resulting in their enhanced stability. The erosion profile of the hydrogels was changeable by the M(n) of PEG-bisamine, independent of the polyrotaxane content. The hydrogels cross-linked by the polyrotaxane can be new candidates as long-term stable but actually hydrolyzable hydrogels for polymeric scaffolding in tissue engineering.

Clonazepam release from bioerodible hydrogels based on semi-interpenetrating polymer networks composed of poly(ε-caprolactone) and poly(ethylene glycol) macromer

Poly(ethylene glycol)(PEG) macromers terminated with acrylate groups and semi-interpenetrating polymer networks (SIPNs) composed of poly(ε-caprolactone)(PCL) and PEG macromer were synthesized to obtain a bioerodible hydrogel. Polymerization of PEG macromer resulted in the formation of cross-linked gels due to the multifunctionality of macromer. Glass transition temperature ( T g) and melting temperature ( T m) of PEG networks and PCL in the SIPNs were inner-shifted, indicating an interpenetration of PCL and PEG chains. Water content in the SIPNs increased with increasing PEG weight fraction due to the hydrophilicity of PEG. The amount of clonazepam (CNZ) released from the SIPNs increased with higher content in the SIPNs, lower drug loading, lower concentration of PEG macromer during the SIPNs preparation, and higher molecular weight of PEG. In particular, a combination with low PEG content and low CNZ solubility in water led to long-term constant release from these matrices in vitro and in vivo.

Synthesis of Polymer Network Scaffolds from l-Lactide and Poly(ethylene glycol) and Their Interaction with Cells

New lactide-based poly(ethylene glycol) (PEG) polymer networks (GL−PEGs) have been prepared by UV photopolymerization using two nontoxic macromers, triacrylated lactic acid oligomer emanating from a glycerol center (GL) and monoacrylated PEG. These materials have been developed for use as polymer scaffolds in tissue engineering, which have cell-adhesion resistant, ligand-immobilizable, and biodegradable characteristics. The GL−PEG cross-linked polymer networks obtained were glassy and transparent, and the gel content was approximately 90%, irrespective of the degree of polymerization of lactide on the glycerol center and the amount and molecular weight of the PEG acrylate incorporated. All networks showed relatively low swelling in water, due to their highly cross-linked nature. They had no melting endotherms, but they displayed glass transition temperatures indicative of phase-mixing of the PEG. Analysis by ESCA, contact angle measurement, and cell culture indicated the presence of PEG at the network surfaces and showed that higher molecular weight PEG was incorporated into the network surfaces to a higher extent, rendered the surfaces more hydrophilic, and repelled cell adhesion more effectively than did PEG of lower molecular weights. All GL networks showed much less adhesion and spreading of human foreskin fibroblasts than glass used as a control. In particular, GL−PEG networks were highly resistant to cell adhesion due to the mobile PEG chains. Given that the terminal hydroxyl function on the incorporated PEG can be readily derivatized with a bioactive peptide, these degradable networks should be useful as polymer scaffolds for tissue engineering.