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Biomedical subjects

B J Tighe

Publications and source records attributed to B J Tighe.

At least 19 recordsLinked to original sources
PubMed2004

Mathematical modelling of corneal swelling.

This paper presents a differential model of the corneal transport system capable of modelling thickness changes in response to osmotic perturbations applied to either limiting membrane. The work is directed towards understanding corneal behaviour in vivo. The model considers the coupled viscous flows within the corneal stroma and across the epithelial and endothelial membranes. The flows within the stroma are established based on transport theory in porous media, while the flows across the membranes are described using the phenomenological equations of irreversible thermodynamics. The ability of the numerical model to reproduce corneal thickness changes in response to endothelial perturbations was tested against available experimental data. The sensitivity of the model to changes in stromal and membrane transport coefficients was examined.

Cell Membrane Permeability↗
PubMed2003

A model for the preliminary biological screening of potential keratoprosthetic biomaterials.

A series of in vitro screening assays for the preliminary selection of biomaterials for use in the fabrication of artificial corneas (keratoprostheses) (KPros) have been investigated. These screening assays assessed the initial binding of inflammatory and cell adhesive proteins, activation of inflammatory proteins, adhesion of keratocytes, epithelial cells and macrophages and the production of inflammatory cytokines by keratocytes contacting biomaterials. Central optic biomaterials were selected on the basis of low-inflammatory and cell adhesion potential. Peripheral skirt materials were selected on the basis of low-inflammatory potential but good cell adhesion to anchor the implant within the host cornea. Green fluorescent protein (GFP) gene transfer was used in a novel context to investigate cell invasion in the absence of external staining techniques. Confocal laser scanning microscopy and scanning electron microscopy were used to investigate GFP positive keratocyte invasion of porous materials. The results of in vitro assays were compared to a corneal organ culture system in which the biomaterials were assessed within a stromal environment. A range of polyurethane-based interpenetrating polymers with a range of water contents were screened. All materials showed low-inflammatory potential. A reduction in biomaterial water content induced an increase in complement C3 and fibronectin binding and in cell adhesion to materials, whilst differences in co-monomer formulation had little impact. The screening methods used in the current study provide a suitable preliminary assessment regime for the in vitro evaluation of potential KPro materials.

Biocompatible Materials↗
PubMed2001

Responsive hydrophobically associating polymers: a review of structure and properties.

Responsive hydrophobically associating polymers can in many ways be considered to be analogous to proteins in their ability to form compact molecules with a defined secondary structure, and hence, functionality. These molecules are characterized by the presence of alternating charged and hydrophobic groups. The balance between charge repulsion and hydrophobic interactions is sensitive to environmental pH and therefore changes in pH produce controllable conformational changes. The change from a charged extended chain to a collapsed uncharged coil structure is sometimes referred to as hypercoiling behaviour and enables the polymer to act as a simple switch between an 'on' and 'off' state. The purpose of this review is to illustrate the structure and behaviour of polymers that exhibit hypercoiling behaviour and to highlight their potential pharmaceutical applications, which in terms of drug delivery is likely to be related to their surface behaviour and solubilizing activity.

Animals↗
PubMed1999

Examination of particulate macroporous hydrogels in an extracorporeal rat haemoperfusion model.

A series of macroporous hydrogels has been synthesized, selected from a range of such materials in which the presence of functional groups has been shown to produce sorbent properties with respect to molecules having clinical significance in the field of liver support. The use of freeze thaw polymerization, together with inverse suspension polymerization in hexane, or in brine, enables macroporous beads ranging in size from 150 to 2000 microm, to be prepared from functional monomers exhibiting a range of chemical functionalities and aqueous solubilities. In order to investigate the behaviour of these rigid porous hydrophilic substrates in haemoperfusion, a rat model was used to explore various aspects of whole blood response. The materials were incorporated into an extracorporeal circuit linking the right carotid artery and left jugular vein of male Sprague-Dawley rats. Erythrocyte, leucocyte and platelet levels were monitored over a 240 min haemoperfusion period. The most significant observation is that, apart from the strongly acidic polyacrylic acid substrate. matrix chemistry has relatively little effect on leucocyte or platelet response. The most important factors appear to be surface area, pore size and surface rugosity, which do produce measurable, but not dramatic differences. This is encouraging for future work, since these variables may be manipulated by polymerization conditions.

Acrylates↗
PubMed1996

Preliminary in vitro cytotoxicity screening of a bead-formed macroporous hydrophilic polymer matrix.

A prescreen of the in vitro cytotoxicity of both the primary fabrication components and potential leachables from a bead-formed macroporous poly(2-hydroxyethyl methacrylate), (pHEMA) matrix has been carried out using INVITTOX Neutral red and Kenacid blue R dye binding methods. Of the eluants obtained from 24, 48, and 72-h incubated beads, only the 72-h eluant produced a greater than 20% (ID20) inhibition of 3T3-L1 cell proliferation with values of 20.98 +/- 2.33% and 21.41 +/- 1.37% inhibition for the Neutral red and Kenacid blue R binding methods, respectively. ID50 values for the fabrication components obtained using the Kenacid blue R method were generally higher than those obtained by the Neutral red assay, although the ranking of the chemicals in terms of their relative cytotoxicities was identical by both methods, i.e. ethylene glycol dimethacrylate > uranyl nitrate > purified HEMA > n-hexane > ethylene glycol (mmol 1(-1)). Whilst extended washing of finished PHEMA beads in water will reduce their acute in vitro cytotoxicity, this will only be achieved with some loss of previously encapsulated water soluble macromolecules.

2,4-Dinitrophenol↗
PubMed1996

Determination of lubricating film thickness for permeable hydrogel and non-permeable polyurethane layers bonded to a rigid substrate with particular reference to cushion form hip joint replacements.

The lubricating film thickness in a model of compliant layered bearings, using both permeable hydrogels and non-permeable polyurethane elastomers for total hip joint replacements, has been measured using optical interferometry, under both entraining and squeeze-film motion. The film thickness in the lubricated contact was measured for both water and a 40 per cent glycerol solution in water as a function of entraining velocity and squeeze-film time. The measured lubricating film thickness for the permeable hydrogel was compared to that of the non-permeable polyurethane elastomer and little difference was found when the lubricating film thickness was sufficiently large (greater than 150 nm). Comparison of the experimental results and the theoretical predictions based upon elastohydrodynamic lubrication analysis showed good agreement in the entraining experiments where the film thickness was greater than 150 nm. In the squeeze-film experiments the experimental measurements were greater than the theoretical predictions for all squeeze times due to the formation of a central pocket of fluid which was not predicted by the simple theory used. This also occurred for the hydrogels for films greater than 150 nm. For longer squeeze times the film thickness for the hydrogel fell below the theoretical prediction. This was considered to be due to the permeability of the hydrogel reducing the film thickness when the film thickness was less than 150 nm. The permeability of the hydrogel was not modelled in the theoretical lubrication analysis used in this study.

Biomechanical Phenomena↗
PubMed1995

The incorporation and sustained release of bioactive insulin from a bead-formed macroporous hydrogel matrix.

Freeze-thaw photopolymerization of a mixed solution of monomers and bovine insulin around frozen ice crystals has been used to generate a bead-formed macroporous hydrophilic matrix of p-HEMA. The largest proportion of beads was 500-1000 microns in size (distribution < 106-1700 microns) with a mean EBC of 71.7 +/- 0.92%. Insulin release was monitored using RIA and insulin bioactivity determined using the rate of insulin stimulated D-[U14C] glucose oxidation to 14CO2. The cumulative insulin release profile was characterized by an initial lag phase followed by an almost linear increase in insulin release for up to 30 days. Insulin release at 4 degrees C was significantly greater than release at 37 degrees C both in the presence and absence of 2.5% thiomersalate as preservative. The latter served to extend the time period over which significant insulin release could be detected. Increasing the monomer concentration decreased the mean equilibrium buffer content (EBC), the total mean cumulative release of insulin, and the proportion of the incorporated insulin load subsequently released at both 4 degrees C and 37 degrees C in the presence of preservative. Insulin determination using RIA and bioassay confirmed that insulin released from beads was bioactive and that immunoreactivity was a reasonably reliable indicator of bioactivity.

Animals↗
PubMed1995

Enzymatic assay of hydroxybutyric acid monomer formation in poly(beta-hydroxybutyrate) degradation studies.

A novel method for monitoring the degradation of poly(beta-hydroxybutyrate) based on the enzymatic assay of beta-hydroxybutyrate (HBA) monomers has been developed. The method is particularly applicable to forms of the polymer, such as fibre and microcapsules, for which conventional surface and gravimetric monitoring techniques are not readily applicable. The method involves the use of enzyme HBA dehydrogenase in a reaction that converts nicotinamide adenine dinucleotide (NAD) to its reduced form (NADH). The conversion is associated with an increase in light absorption at 340 nm which thus serves to indicate the concentration of HBA monomer in the sample. The application of the methodology to the degradation of poly(beta-hydroxybutyrate) gel spun fibres has been used to demonstrate its potential use as a quantitative monitoring technique in the study of the hydrolysis of this polymer.

Hydrogen-Ion Concentration↗
PubMed1994

The incorporation and release of glucose oxidase and interleukin 2 from a bead formed macroporous hydrophilic polymer matrix.

Freeze-thaw photopolymerization at low temperature of a mixed solution of 2-hydroxyethyl methacrylate (HEMA), ethylene glycol dimethacrylate (EDM), and either glucose oxidase (GOx) or interleukin 2 (IL-2) around frozen ice crystals has been used to generate a bead-formed macroporous hydrophilic matrix with potential for immobilization and sustained release. The mean equilibrium acetate buffer content (EBC) of unloaded p-HEMA beads at room temperature and controlled humidity was approximately 72%. The incorporation of GOx into beads significantly increased the EBC to approximately 76%. The release of GOx was characterized by a short initial burst release which declined rapidly until by day 14 no further biologically active enzyme release could be detected. Bead size had no significant effect on the total mean cumulative release of GOx at room temperature. Since only approximately 4% of the original therapeutic load of GOx was released over 14 days a substantial proportion of biologically active enzyme had become associated with the hydrogel matrix surface generating a bead formed immobilised enzyme system. Total cumulative release profiles for IL-2 were almost linear and maintained for at least 16 days. In absolute terms, the proportion of the original theoretical incorporated load subsequently released over this period was low. However, such a low level sustained release of IL-2 may lend itself therapeutically to a reduction in unwanted non-specific systemic activity.

Enzymes, Immobilized↗
PubMed1993

Incorporation and release of fluorescein isothiocyanate-linked dextrans from a bead-formed macroporous hydrophilic matrix with potential for sustained release.

Freeze-thaw polymerization has been used to generate a bead-formed (100-3000 microns) macroporous hydrophilic matrix with potential for the sustained release of macromolecules. While the incorporation of FITC-dextrans marginally increased the equilibrium water content, their in vitro release profiles were characterized by an initial burst followed by a low but sustained release lasting > 21 d. The total cumulative release of FD-150 and the percentage of the incorporated FD-150 load subsequently released were reduced compared with FD-20S but for both dextrans these parameters could be enhanced by increasing the bead size and increasing the incubation temperature to 37 degrees C.

Biocompatible Materials↗
PubMed1993

Macroporous hydrogels for biomedical applications: methodology and morphology.

Macroporous hydrogel membranes have been fabricated using two complementary techniques, both involving the polymerization of a solution of monomers around a crystalline matrix which is subsequently removed. The first of these is the freeze-thaw technique, in which aqueous systems are used to form ice-based crystalline matrices. Whereas in the second, the porosigen technique, a crystalline compound (e.g. sucrose) is dispersed in the monomer solution prior to polymerization. Both copolymer composition and the polymerization conditions were found to influence membrane morphology and the limitations in the range of morphologies attainable using each technique are discussed. Careful choice of technique and polymerization conditions enables macroporous hydrogels with a wide range of morphologies to be fabricated, which are potentially valuable in a variety of biomedical applications. The suitability of these techniques described for the production of materials for use in affinity chromatography, as cell separation substrates and as synthetic articular cartilage as well as more general areas of biomedicine, is discussed.

3T3 Cells↗
PubMed1993

Towards a synthetic articular cartilage.

The physical and morphological properties of articular cartilage have been used as a model for the preparation of hydrogel based synthetic analogues of this complex high water content natural hydrogel. The relatively poor strength and stiffness of simple homogeneous hydrogels have been enhanced by semi-interpenetrating polymer network (semi-IPN) technology to a level which enables the mechanical properties of natural cartilage to be approached. Maintenance of chondrocytic phenotypes at the implant interface in vitro has been found to require careful control of pore size and distribution in the hydrogel matrix. The study of synthetic techniques for the fabrication of macroporous semi-IPNs has enabled hydrogel semi-IPNs with appropriate pore sizes and mechanical properties to be produced. A range of in vitro testing techniques have been developed to enable the physico-chemical properties of these materials to be optimised prior to animal studies.

Animals↗
PubMed1992

Polymers for biodegradable medical devices. VIII. Hydroxybutyrate-hydroxyvalerate copolymers: physical and degradative properties of blends with polycaprolactone.

The physical and degradative properties of polyhydroxybutyrate-hydroxyvalerate copolymer blends with polycaprolactone were investigated. Blends containing low levels of polycaprolactone (less than 20%) were found to possess a considerable degree of compatibility, whilst those with higher levels of polycaprolactone were incompatible and showed phase separation behaviour. This incompatibility was most marked in blends containing approximately 50% of each component. In blends containing low levels of polycaprolactone, processing conditions governed the ease of crystallization of polycaprolactone in the polyhydroxybutyrate-hydroxyvalerate matrix and thus the mechanical property of the blend. The degradation rate of these blends was found to be influenced by a complex set of factors, including temperature, pH and polycaprolactone content of the blend. Although crystallinity affected the mechanical properties of the blends, its influence on the hydrolytic degradation rate was masked by the large difference in the molecular weight of the polyhydroxybutyrate-hydroxyvalerate copolymers (MW approximately 300,000) and polycaprolactone. (MW approximately 50,000). The polyhydroxybutyrate-hydroxyvalerate/polycaprolactone blends were found to be much more stable to hydrolytic degradation than polyhydroxybutyrate-hydroxyvalerate/polysaccharide blends previously studied. Here the combined techniques of goniophotometry and surface energy measurements proved extremely valuable in monitoring the early stages of degradation, during which surface, rather than bulk degradation, processes predominate.

Biocompatible Materials↗
PubMed1992

Polymer membranes in clinical sensor applications. I. An overview of membrane function.

Polymer membranes are used in a wide variety of molecular sensing devices many of which are of potential clinical interest. The role of the polymer and the physical properties required of it are, however, rarely clearly defined. An extensive review is presented of the range of polymers whose use as membranes is described in the sensor literature. This forms the basis of an overview of membrane function in potentiometric amperometric and fibre optic sensors. In particular, the interaction of permeability, permselectivity and transmembrane potential is highlighted, together with the role of polymer membranes as matrices for the immobilization of reactive chemical and biological agents.

Biocompatible Materials↗
PubMed1992

Polymer membranes in clinical sensor applications. II. The design and fabrication of permselective hydrogels for electrochemical devices.

Hydrogels, particularly the tough, low water content materials, have potential advantages in the field of clinical biosensors because of their established use as medical polymers. The factors that control transport behaviour in these polymers are discussed with particular reference to ion selectivity. The nature of the transport behaviour in relation to coated wire electrode performance is presented and an extension of these permselectivity studies to the fabrication of miniaturized devices, such as ISFETs, is described. Linear soluble hydrogel polymers, coated on to sensor substrates, may be converted to insoluble membranes using solid photosensitive aromatic monomers, such as N-vinyl carbazole. Photolithographic patterning is achieved using a UV source together with appropriate masking, followed by an oxygen plasma etch process. Gas plasma etching, which selectively removes uncross-linked (masked) areas forms the basis of an all dry, low-temperature patterning process capable of giving micrometre-scale resolution. This novel photographic process, which does not damage or extract enzymes or ionophores, can advantageously be extended to the fabrication of poly(vinylchloride)-based membranes.

Biocompatible Materials↗
PubMed1992

Polymer membranes in clinical sensor applications. III. Hydrogels as reactive matrix membranes in fibre optic sensors.

The potential of hydrogel copolymer membranes in clinical sensors, based on fibre optics, is addressed. The particular properties of the membranes of relevance in this application are the ease of refractive index modulation and the potential of the hydrogel to act as a permselective barrier in which a colorimetric agent may be immobilized. The results presented illustrate the complexity of colorimetric and refractive index effects together with their dependence on pH and tonicity for hydrogels of a given composition range. The incorporation of an acryloyl-functionalized reagent (bromopyrogallol red) is used to illustrate the way in which a working pH sensor based on these combined properties may be designed and fabricated.

Biocompatible Materials↗