Interpenetrating polymer networks of alginate and polyethylene glycol for encapsulation of islets of Langerhans.

A mixture of alginate and polyethylene glycol acrylate was investigated as a system for the encapsulation of islets of Langerhans. This system showed dual crosslinkability: the alginate was ionically crosslinked by multivalent cations, and the PEG was covalently crosslinked by photoactivated free radical polymerization. The major advantage of the dually crosslinkable system was the chemical stability of the resultant gels due to the presence of covalent bonds that maintain the integrity of the gel as opposed to reversible ionic linkages that were the only mode of crosslinkage in previous generations of alginate-based encapsulation systems. The physical aspects of gelation of such alginate/PEG compositions were investigated. Diffusion of dextrans of known molecular weights through these gels was studied in order to shed light on the hydrogel porosity and permeability. In vitro viability and function tests demonstrated that these gels were biocompatible. Islets encapsulated in these systems were healthy and retained both viability and insulin secretory function.

Homonymous visual field defects in patients without corresponding structural lesions on neuroimaging.

Homonymous visual field defects usually occur with structural processes affecting retrochiasmal visual pathways. The responsible lesion is usually evident on magnetic resonance imaging or on other neuroimaging studies. When results of neuroimaging are normal, functional illness is often suspected. The authors report four patients with homonymous visual field defects who presented with no evident corresponding lesion on magnetic resonance or computed tomography imaging. Etiologies for the visual field defects included the Heidenhain variant of Creutzfeldt-Jacob disease, degenerative dementia, subtle occipital ischemia demonstrated only on positron-emission tomography scanning, and nonketotic hyperglycemia. Clinicians should be aware of the alternative etiologies of organic homonymous visual field loss in patients with normal neuroimaging.

Internuclear ophthalmoplegia after coronary artery catheterization and percutaneous transluminal coronary balloon angioplasty.

A retrospective chart review was performed for identification of patients with isolated internuclear ophthalmoplegia (INO) postcardiac catheterization from two neuro-ophthalmology units. Of the 110 patients with a diagnosis of INO who were evaluated during the observation period, five patients (4.5%) demonstrated relatively isolated INO occurring in the perioperative period of a cardiac endovascular procedure. These five patients underwent diagnostic catheterization alone (three patients), balloon angioplasty (one patient), or stent placement (one patient). All patients improved, with resolution of diplopia in primary position after a mean period of 82 days. The occurrence of INO in the postcardiac catheterization setting is not uncommon, and it appears to be related to dorsal pontine ischemia. The pontomesencephalic medial longitudinal fasciculus is supplied by small-caliber perforating end-arteries from the basilar trunk, which increases selective vulnerability of this area. Cardiac catheterization may precipitate microemboli involving these vessels, leading to internuclear ophthalmoplegia.

Molecular mass distribution of sodium alginate by high-performance size-exclusion chromatography.

A sensitive high-performance size-exclusion chromatography (HPSEC) method with simple UV detection was developed for the molecular mass analysis of sodium alginate. It was used to evaluate alginates of varying molecular mass and the results were compared with the viscosity measurements. This HPSEC method was sensitive to serve as the stability indicating method for alginate after storage under different conditions. The information of relative molecular mass distribution of alginate was provided with reference to pullulan molecular mass standards. The comparison of the HPSEC chromatograms of alginate, pullulan and dextran revealed the effect of chemical composition of a polysaccharide and its effect on apparent molecular mass distribution.

Surface-immobilized polyethylene oxide for bacterial repellence.

Polyethylene terephthalate films were surface-modified with polyethylene oxide (18,500 g/mol) using a solution technique described previously. These films were investigated for their resistance to bacterial adhesion. Three bacterial strains most commonly associated with implant infections, Staphylococcus epidermidis, Staphylococcus aureus and Pseudomonas aeruginosa, were cultured in tryptic soya broth, human plasma and human serum on the polymeric substrates. Significant reductions (between 70 and 95%) in adherent bacteria were observed on the polyethylene oxide-modified substrates compared to the untreated control polyethylene terephthalate. Surface modification with polyethylene oxide may reduce the risk of implant-associated infections. Plasma fibrinogen was observed to play an important role in the adhesion of all three of these species on both the polyethylene oxide-modified and control polyethylene terephthalate materials.

Tissue response to intraperitoneal implants of polyethylene oxide-modified polyethylene terephthalate.

Polyethylene terephthalate films surface modified with polyethylene oxide of mol wt 18,500 g/mol (18.5 k) by a previously described technique, were implanted in the peritoneal cavity of mice, along with their respective untreated controls, for periods of 1-28 d. The implants were retrieved and examined for tissue reactivity and cellular adherence. The control polyethylene terephthalate surfaces showed an initial inflammatory reaction followed by an extensive fibrotic response with a mean thickness of 60 microns at 28 d. By contrast, polyethylene oxide-modified polyethylene terephthalate showed only a mild inflammatory response and no fibrotic encapsulation throughout the implantation period: at 28 d a cellular monolayer was observed. Apparently either the polyethylene oxide-modified surface was stimulating less inflammation, which was in turn stimulating less fibroblastic overgrowth, or the cellular adhesion to the polyethylene oxide-modified surface was too weak to support cellular multilayers.

Biological responses to polyethylene oxide modified polyethylene terephthalate surfaces.

Polyethylene oxide (PEO) of molecular weights 5,000, 10,000, 18,500, and 100,000 g/mol was covalently grafted to surfaces of otherwise cell adhesive polyethylene terephthalate (PET) films. Analysis of these surfaces by measurement of contact angles and ESCA verified the presence of the grafted PEO. Protein adsorption assays of radiolabeled albumin and fibrinogen showed a marked reduction in adsorbed protein for the 18,500 and 100,000 molecular weight PEO coupled surfaces. Cell growth assays using human foreskin fibroblasts in culture showed that the higher-molecular-weight PEO surfaces supported cell growth to a much lower extent than the two lower-molecular-weight PEOs. Flow of whole blood over these surfaces and visualization of platelet adherence using epifluorescence video-microscopy showed very low platelet adherence only on the two higher-molecular-weight PEO coupled surfaces. Scanning electron microscopy corroborated these results. It was concluded that PEO of molecular weights neighboring 18,500 and higher was effective in reducing protein adsorption and cellular interactions on these surfaces.

Endothelial cell-selective materials for tissue engineering in the vascular graft via a new receptor.

We have found a novel adhesion receptor on the human endothelial cell for the peptide sequence Arg-Glu-Asp-Val (REDV), which is present in the III-CS domain of human plasma fibronectin, with a dissociation constant of 2.2 x 10(-6) M and 5.8 x 10(6) sites/cell. When a synthetic peptide containing this sequence was immobilized on otherwise cell nonadhesive substrates, endothelial cells attached and spread but fibroblasts, vascular smooth muscle cells, and platelets did not. Endothelial monolayers on REDV were nonthrombogenic: endothelial cells attached and spread upon other receptor-binding domains of fibronectin and laminin, but with lesser degrees of specificity or with a loss of nonthrombogenicity. This approach may provide a basis for a tissue engineered vascular graft where endothelial cell attachment is desired, but not the attachment of other blood vessel wall cells and blood platelets.

Solution technique to incorporate polyethylene oxide and other water-soluble polymers into surfaces of polymeric biomaterials.

A simple solution technique was used to incorporate polyethylene oxide (PEO, of 5000, 10,000, 18,500, and 100,000 g/mol) and other water-soluble polymers such as polyvinylpyrrolidone and polyethyl oxazoline into the surfaces of commonly used biomedical polymers such as polyethylene terephthalate, a polyurethane (Pellethane 2363-80AE), and polymethylmethacrylate. The presence of the water-soluble polymers on these surfaces was verified by using contact angle analysis and ESCA. Protein adsorption studies, fibroblast adhesion assays, and whole blood perfusions over these polymers showed that the surface modified with PEO 18,500 was the most effective in reducing all the tested biological interactions. It was concluded that PEO 18,500 had a chain length that was optimal, using this technique for surface incorporation, to reduce protein adsorption and hence prevent protein-mediated biological interactions.

The short-term blood biocompatibility of poly(hydroxyethyl methacrylate-co-methyl methacrylate) in an in vitro flow system measured by digital videomicroscopy.

An in vitro flow system for short-term blood biocompatibility testing of solution-castable polymeric biomaterials was developed. This system was relatively free of artefacts resulting from blood contact with materials other than the test material itself. In conjunction with epifluorescence videomicroscopy and digital image processing, this method provided a high resolution, quantitative, continuous analysis of platelet adhesion, aggregation, thrombus formation, and embolization on the biomaterial surface. This system was well suited for performing biochemical assays on post-contact blood for assessment of platelet activation and release as additional measures of the thrombogenicity of the test material. This method for biomaterials evaluation in vitro was demonstrated by a detailed examination of copolymers of hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA). Videomicroscopic analysis of fluorescently labelled platelets adhering per unit area of the polymer surface after 5 min of flow at a wall shear rate of 500 s-1 showed a dramatic decrease with increasing HEMA fraction in the polymer. The release of serotonin and thromboxane A2 by platelets decreased with increasing HEMA fraction. Reflection interference contrast microscopy was used to examine focal contacts of platelets on the copolymer surfaces as a qualitative measure of the platelet-surface interaction. A polymer-dependent gradation in contact extent and morphology was observed, ranging from large contacts on P(MMA) to none on P(HEMA).