Designed biodegradable hydrogel structures prepared by stereolithography using poly(ethylene glycol)/poly(D,L-lactide)-based resins

Designed three-dimensional biodegradable poly(ethylene glycol)/poly(D,L-lactide) hydrogel structures were prepared for the first time by stereolithography at high resolutions. A photopolymerisable aqueous resin comprising PDLLA-PEG-PDLLA-based macromer, visible light photo-initiator, dye and inhibitor in DMSO/water was used to build the structures. Porous and non-porous hydrogels with well-defined architectures and good mechanical properties were prepared. Porous hydrogel structures with a gyroid pore network architecture showed narrow pore size distributions, excellent pore interconnectivity and good mechanical properties. The structures showed good cell seeding characteristics, and human mesenchymal stem cells adhered and proliferated well on these materials.

Designed poly(ethylene glycol)/poly(D,L-lactide)-based hydrogel structures prepared by stereolithography

Three-dimensional biodegradable poly(ethylene glycol)/poly(D,L-lactide) hydrogel structures were prepared by stereolithography. A photo-polymerisable liquid resin comprising PDLLA-PEG-PDLLA-based macromer, visible light photo-initiator, dye and inhibitor in DMSO/water was used to build the structures. Hydrogels with welldefined architectures and good mechanical properties were prepared. Hydrogel structures with a gyroid pore network architecture showed narrow pore size distributions, excellent pore interconnectivity and good mechanical properties. The structures showed good cell seeding characteristics, and human mesenchymal stem cells adhered and proliferated on these materials.

Melt electrospinning of polycaprolactone and its blends with poly(ethylene glycol)

Melt electrospinning is one aspect of electrospinning with relatively little published literature, although the technique avoids solvent accumulation and/or toxicity which is favoured in certain applications. In the study reported, we melt-electrospun blends of poly(ε-caprolactone) (PCL) and an amphiphilic diblock copolymer consisting of poly(ethylene glycol) and PCL segments (PEG-block-PCL). A custom-made electrospinning apparatus was built and various combinations of instrument parameters such as voltage and polymer feeding rate were investigated. Pure PEG-block-PCL copolymer melt electrospinning did not result in consistent and uniform fibres due to the low molecular weight, while blends of PCL and PEG-block-PCL, for some parameter combinations and certain weight ratios of the two components, were able to produce continuous fibres significantly thinner (average diameter of ca 2 µm) compared to pure PCL. The PCL fibres obtained had average diameters ranging from 6 to 33 µm and meshes were uniform for the lowest voltage employed while mesh uniformity decreased when the voltage was increased. This approach shows that PCL and blends of PEG-block-PCL and PCL can be readily processed by melt electrospinning to obtain fibrous meshes with varied average diameters and morphologies that are of interest for tissue engineering purposes. Copyright © 2010 Society of Chemical Industry

Effect of dangling chains on the structure and physical properties of a tightly crosslinked poly(ethylene glycol) network

Major imperfections in crosslinked polymers include loose or dangling chain ends that lower the crosslink d., thereby reducing elastic recovery and increasing the solvent swelling. These imperfections are hard to detect, quantify and control when the network is initiated by free radical reactions. As an alternative approach, the sol-​gel synthesis of a model poly(ethylene glycol) (PEG-​2000) network is described using controlled amts. of bis- and mono-​triethoxy silyl Pr urethane PEG precursors to give silsesquioxane (SSQ, R-​SiO1.5) structures as crosslink junctions with a controlled no. of dangling chains. The effect of the no. of dangling chains on the structure and connectivity of the dried SSQ networks has been detd. by step-​crystn. differential scanning calorimetry. The role that micelle formation plays in controlling the sol-​gel PEG network connectivity has been studied by dynamic light scattering of the bis- and mono-​triethoxy silyl precursors and the networks have been characterized by 29Si solid state NMR, sol fraction and swelling measurements. These show that the dangling chains will increase the mesh size and water uptake. Compared to other end-​linked PEG hydrogels, the SSQ-​crosslinked networks show a low sol fraction and high connectivity, which reduces solvent swelling, degree of crystallinity and the crystal transition temp. The increased degree of freedom in segment movement on the addn. of dangling chains in the SSQ-​crosslinked network facilitates the packing process in crystn. of the dry network and, in the hydrogel, helps to accommodate more water mols. before reaching equil.

methoxy-poly(ethylene glycol) modified poly(L-lactide) enhanced cell affinity of human bone marrow stromal cells by the upregulation of 1-cadherin and delta-2-catenin

Poly(l-lactide) (PLLA), a versatile biodegradable polymer, is one of the most commonly-used materials for tissue engineering applications. To improve cell affinity for PLLA, poly(ethylene glycol) (PEG) was used to develop diblock copolymers. Human bone marrow stromal cells (hBMSCs) were cultured on MPEG-b-PLLA copolymer films to determine the effects of modification on the attachment and proliferation of hBMSC. The mRNA expression of 84 human extracellular matrix (ECM) and adhesion molecules was analyzed using RT-qPCR to understand the underlying mechanisms. It was found that MPEG-b-PLLA copolymer films significantly improved cell adhesion, extension, and proliferation.This was found to be related to the significant upregulation of two adhesion genes, CDH1 and CTNND2, which encode 1-cadherin and delta-2-catenin, respectively, two key components for the cadherin-catenin complex. In summary, MPEG-b-PLLA copolymer surfaces improved initial cell adhesion by stimulation of adhesion molecule gene expression.

Controlling microencapsulation and release of micronized proteins using poly(ethylene glycol) and electrospraying

The fabrication of tailored microparticles for delivery of therapeutics is a challenge relying upon a complex interplay between processing parameters and materials properties. The emerging use of electrospraying allows better tailoring of particle morphologies and sizes than current techniques, critical to reproducible release profiles. While dry encapsulation of proteins is essential for the release of active therapeutics from microparticles, it is currently uncharacterized in electrospraying. To this end, poly(ethylene glycol) (PEG) was assessed as a micronizing and solubilizing agent for dry protein encapsulation and release from electrosprayed particles made from polycaprolactone (PCL). The physical effect of PEG in protein-loaded poly(lactic-co-glycolic acid) (PLGA) particles was also studied, for comparison. The addition of 5–15 wt% PEG 6 kDa or 35 kDa resulted in reduced PCL particle sizes and broadened distributions, which could be improved by tailoring the electrospraying processing parameters, namely by reducing polymer concentration and increasing flow rate. Upon micronization, protein particle size was reduced to the micrometer domain, resulting in homogenous encapsulation in electrosprayed PCL microparticles. Microparticle size distributions were shown to be the most determinant factor for protein release by diffusion and allowed specific control of release patterns.

Treatment of silk fibroin with poly(ethylene glycol) for the enhancement of corneal epithelial cell growth

A silk protein, fibroin, was isolated from the cocoons of the domesticated silkworm (Bombyx mori) and cast into membranes to serve as freestanding templates for tissue-engineered corneal cell constructs to be used in ocular surface reconstruction. In this study, we sought to enhance the attachment and proliferation of corneal epithelial cells by increasing the permeability of the fibroin membranes and the topographic roughness of their surface. By mixing the fibroin solution with poly(ethylene glycol) (PEG) of molecular weight 300 Da, membranes were produced with increased permeability and with topographic patterns generated on their surface. In order to enhance their mechanical stability, some PEG-treated membranes were also crosslinked with genipin. The resulting membranes were thoroughly characterized and compared to the non-treated membranes. The PEG-treated membranes were similar in tensile strength to the non-treated ones, but their elastic modulus was higher and elongation lower, indicating enhanced rigidity. The crosslinking with genipin did not induce a significant improvement in mechanical properties. In cultures of a human-derived corneal epithelial cell line (HCE-T), the PEG treatment of the substratum did not improve the attachment of cells and it enhanced only slightly the cell proliferation in the longer term. Likewise, primary cultures of human limbal epithelial cells grew equally well on both non-treated and PEG-treated membranes, and the stratification of cultures was consistently improved in the presence of an underlying culture of irradiated 3T3 feeder cells, irrespectively of PEG-treatment. Nevertheless, the cultures grown on the PEG-treated membranes in the presence of feeder cells did display a higher nuclear-to-cytoplasmic ratio suggesting a more proliferative phenotype. We concluded that while the treatment with PEG had a significant effect on some structural properties of the B. mori silk fibroin (BMSF) membranes, there were minimal gains in the performance of these materials as a substratum for corneal epithelial cell growth. The reduced mechanical stability of freestanding PEG-treated membranes makes them a less viable choice than the non-treated membranes.

Effect of Interfacial Microstructure of Adsorbed Poly(ethylene glycol) Monooleate on Steel Substrate on Sliding Friction in Oil in Water Emulsion

The concentration of a nonionic surfactant and water pH were varied in an oil-in-water emulsion to minimize the friction coefficient between a steel ball sliding on a steel flat. At a surfactant concentration near the CMC (critical micelle concentration) the oil droplet size was found to be minimum. In this paper we study the microstructure of the surfactant molecules self-assembled on the steel substrate in water to comment on the ability of the surfactant aggregate to attract and retain oil. We find that a near semicylindrical hemimiceller microstructure with hydrocarbon tails projecting into bulk water as obtained at CMC in near neutral water is best able to capture and retain oil in yielding a low coefficient of friction.

Orthogonal biofunctionalization of magnetic nanoparticles via ``clickable'' poly(ethylene glycol) silanes: a ``universal ligand'' strategy to design stealth and target-specific nanocarriers

The present work demonstrates a novel strategy to synthesize orthogonally bio-engineered magnetonanohybrids (MNPs) through the design of versatile, biocompatible linkers whose structure includes: (i) a robust anchor to bind with metal-oxide surfaces; (ii) tailored surface groups to act as spacers and (iii) a general method to implement orthogonal functionalizations of the substrate via ``click chemistry''. Ligands that possess the synthetic generality of features (i)-(iii) are categorized as ``universal ligands''. Herein, we report the synthesis of a novel, azido-terminated poly(ethylene glycol) (PEG) silane that can easily self-assemble on MNPs through hetero-condensation between surface hydroxyl groups and the silane end of the ligand, and simultaneously provide multiple clickable sites for high density, chemoselective bio-conjugation. To establish the universal-ligand-strategy, we clicked alkyl-functionalized folate onto the surface of PEGylated MNPs. By further integrating a near-infrared fluorescent (NIRF) marker (Alexa-Fluor 647) with MNPs, we demonstrated their folate-receptor mediated internalization inside cancer cells and subsequent translocation into lysosomes and mitochondria. Ex vivo NIRF imaging established that the azido-PEG-silane developed in course of the study can effectively reduce the sequestration of MNPs by macrophage organs (viz. liver and spleen). These folate-PEG-MNPs were not only stealth and noncytotoxic but their dual optical and magnetic properties aided in tracking their whereabouts through combined magnetic resonance and optical imaging. Together, these results provided a strong motivation for the future use of the ``universal ligand'' strategy towards development of ``smart'' nanohybrids for theragnostic applications.

Biodegradable Interpolyelectrolyte Complexes Based on Methoxy Poly(ethylene glycol)-b-poly(alpha,L-glutamic acid) and Chitosan

We synthesized methoxy poly(ethylene glycol)-b-poly(alpha,L-glutamic acid) (mPEGGA) diblock copolymer by ring-opening polymerization of N-carboxy anhydride of gamma-benzyl-L-glutamate (NCA) using amino-terminated methoxy polyethylene glycol (mPEG) as macroinitiator. Polyelectrolyte complexation between mPEGGA as neutral-block-polyanion and chitosan (CS) as polycation has been scrutinized in aqueous solution as well as in the solid state.

A Biodegradable Diblcok Copolymer Poly(ethylene glycol)-block-poly(L-lactide-co-2-methyl-2-carboxyl-propylene carbonate): Docetaxel and RGD Conjugation

A diblcok copolymer monomethoxy poly (ethylene glycol)-block-poly(L-lactide-co-2-methyl-2-carboxyl-propylene carbonate) (MPEG-b-P(LA-co-MCC)) was obtained by copolymerization of L-lactide (LA) and 2-methyl-2-benzoxycarbonyl-propylene carbonate (MBC) and subsequent catalytic hydrogenation. The pendant carboxyl groups of the copolymer MPEG-b-P(LA-co-MCC) were conjugated with antitumor drug docetaxel and tripeptide arginine-glycine-aspartic acid (RGD), respectively.

Selective hydrogenation of unsaturated aldehydes in a poly(ethylene glycol)/compressed carbon dioxide biphasic system

Hydrogenation of alpha,beta-unsaturated aldehydes (citral, 3-methyl-2-butenal, cinnamaldehyde) has been studied with tetrakis(triphenylphosphine) ruthenium dihydride (H2Ru(TPP)(4)) catalyst in a poly(ethylene glycol) (PEG)/ compressed carbon dioxide biphasic system. The hydrogenation reaction was slow under PEG/ H-2 biphasic conditions at H-2 4 MPa in the absence of CO2. When the reaction mixture was pressurized by a non-reactant of CO2, however, the reaction was significantly accelerated.