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Biomedical subjects

B J Tighe

Publications and source records attributed to B J Tighe.

34 records · Page 2Linked to original sources

Low temperature incorporation of bovine serum albumin into a bead formed macroporous hydrophilic polymer matrix with potential for sustained release.

A process of freeze-thaw polymerization involving the low temperature photopolymerization of a mixed solution of monomers and bovine serum albumin around frozen ice crystals has been used to generate a bead formed macroporous hydrophilic matrix with potential for sustained release. Beads over the size range 100-3000 microns were fabricated with surface and internal pores of between 0.7-2.6 microns whose diameter could be controlled by manipulation of the monomers to solvent ratio. Increasing both the proportion of monomers in the monomer solution and the percentage of BSA incorporated reduced the EWC of beads. The BSA release profile was characterized by an initial burst followed by a lower but sustained release lasting up to 1 month. The total cumulative release of BSA and the proportion of the incorporated BSA load subsequently released were both reduced in physiological saline compared with distilled water but enhanced by freeze drying, mild agitation and incubation at 37 degrees C.

Cold Temperature↗

Polymers for biodegradable medical devices. V. Hydroxybutyrate-hydroxyvalerate copolymers: effects of polymer processing on hydrolytic degradation.

The effects of melt processing on those properties of polyhydroxybutyrate-hydroxyvalerate copolymers that control hydrolytic stability were studied. Initial experiments using a non-thermal preparation technique enabled the relationship between initial molecular weight and rate of hydrolytic degradation to be established. This rate was conveniently expressed in terms of the time for 10% by weight of the sample to be eroded. By varying melt processing conditions, the range of effects of processing on sample molecular weight and molecular weight distribution were investigated. These effects were found to be quite dramatic, with a reduction to 50% of the initial molecular weight being readily achieved. Temperature, shear rate and dwell time interrelated to control the extent of thermal degradation achieved during processing. The principal effect of copolymer composition resulted from the fact that an increase in hydroxyvalerate content led to a reduction in melting point and enabled milder processing conditions to be used. Enhanced crystallinity, resulting from more favourable processing conditions reduced hydrolytic degradation rates. As a result, melt processing produced a complex interrelation of effects, all of which influenced the hydrolytic stability of the fabricated specimen. In general, molecular weight effects predominated.

Biodegradation, Environmental↗

Polymers for biodegradable medical devices. VII. Hydroxybutyrate-hydroxyvalerate copolymers: degradation of copolymers and their blends with polysaccharides under in vitro physiological conditions.

The hydrolytic degradation of hydroxybutyrate-hydroxyvalerate copolymers was monitored in vitro at 37 degrees C and pH 7.4. Direct use of bulk properties such as weight loss and tensile strength did not reveal substantial changes in the polymer matrix over degradation periods of several months. Despite this, the polymers were demonstrated to undergo significant modification during this period, in ways that markedly influence their subsequent behaviour. Combined use of goniophotometry and surface energy measurements revealed that surface modification begins at an early stage and is accompanied by diffusion of water into the matrix and a progressive increase in polymer porosity. Relatively little change in the molecular weight and some increase in the crystallinity of the matrix occurred during these early months. As a result, the tensile strength of the polymer varies little in this period. As the porosity of the matrix increases, hydrolytic chain scission within the matrix and diffusion out of degradation products proceeds more effectively. Decrease in matrix molecular weight, increase in matrix erosion, weight loss and loss of tensile strength began at a much more dramatic rate. The apparent resistance of the polymer to degradation in the early months is followed by an accelerated degradation phase around and beyond 1 yr. The use of filters that can dissolve or hydrolytically degrade more rapidly than the hydroxybutyrate matrix accelerates the development of porosity within the matrix and thus enhances the decomposition process.

Biocompatible Materials↗

The potential of hydrogels as synthetic articular cartilage.

The relatively poor mechanical properties of conventional synthetic hydrogels are illustrated and compared with those of articular cartilage. By using the composite structure of the natural material as a model a new family of hydrogels, based on interpenetrating polymer network (IPN) technology, has been developed. The underlying synthetic strategies are discussed and the properties of a novel representative network presented. IPN formation produces networks that are stiffer and stronger than the hydrogel copolymers of similar water content. In this behaviour these simple IPNs begin to mimic the properties of biological hydrogel composites. Thus, these materials have exciting potential for demanding in vivo applications.

Biocompatible Materials↗

Synthetic hydrogels. VI. Hydrogel composites as wound dressings and implant materials.

An overview is presented of the use of hydrogel composites as biomaterials. These range from laminates or coatings (in which a homogeneous hydrogel is used in conjunction with a more mechanically stable substrate), through blends of hydrogels with synthetic hydrophobic polymers, to the use of two-component systems in which water enhances the compatibility of two structurally different polymers. Although synthetic hydrogels provide an ideal basis for materials of these types, naturally occurring hydrophilic polymers with their unique properties have a major contribution to make. It is in the clinical and patent literature, rather than journals dealing with polymers per se, that the vast majority of examples of the use of hydrogel composites are found. This review collects and comments on examples based on synthetic developments in this field during the last decade, particularly in relation to the development of wound dressings and implant materials.

Bandages↗

Polymers for biodegradable medical devices. VI. Hydroxybutyrate-hydroxyvalerate copolymers: accelerated degradation of blends with polysaccharides.

The hydrolytic degradation of poly(hydroxybutyrate)-poly(hydroxyvalerate) (PHB-PHV) copolymers in the form of blends with the polysaccharides amylose, dextran, dextrin and sodium alginate, has been studied under a range of conditions (pH 2.3, 7.4 and 10.6 and at 37 degrees C and 70 degrees C). The hydrolytic degradation of the PHB-PHV copolymers was found to be dramatically affected by the presence of polysaccharides. Its progress was characterized by an initial increase in the wet weight, with concurrent decrease in the dry weight as the polysaccharides eroded from the matrix. Surface energy measurements and goniophotometry proved to be particularly useful in monitoring this stage of the degradation process. The concurrent increase in internal porosity leads to the eventual collapse of the matrix, a process which occurs, but less rapidly, in the degradation of the unblended PHB-PHV copolymers. Information obtained from molecular weight and crystallinity studies enabled a comprehensive profile of the overall degradation process to be built up.

Alginates↗

Polymers for biodegradable medical devices. III. Polymerization and copolymerization of cyclic derivatives of tartronic acid.

The syntheses of anhydrosulphite and anhydrocarboxylate derivatives of tartronic acid are described. These compounds, more correctly named 5-carboxy-1,3,2-dioxathiolan-4-one-2-oxide and 5-carboxy-1,3-dioxolan-2,4-dione have been shown to undergo polymerization and copolymerization to poly-alpha-esters containing the tartonic acid residue, characterized by the presence of a pendant carboxyl group. Thermal polymerization of the anhydrosulphite appears to proceed in a substantially identical manner to other members of the series in which the monomer decomposes by a first order process to yield an alpha-lactone which polymerizes by a rapid chain growth reaction. Because the rate of thermal polymerization of tartronic acid anhydrosulphite is much more rapid than simple alkyl substituted anhydrosulphites, copolymerization favours the former residues. More successful copolymerization was achieved by the use of tertiary base initiators and the anhydrocarboxylate derivative of tartronic acid. The polymers and copolymers described are of potential value in the synthesis of drug-carrying biodegradable matrices or more hydrophilic analogues of poly(glycolic acid) which combine the known bioerodibility of the moiety with that presence of a pendant carboxyl group.

Biocompatible Materials↗

Studies of the ocular compatibility of hydrogels. White spot deposits--chemical composition and geological arrangement of components.

Light, SEM and histochemical techniques were used to determine the architecture and composition of elevated deposits on a variety of commercial lenses of differing bulk and surface chemistries and wear protocols. Spoilt lenses were derived from controlled lens wear trials and additional clinical sources. Elevated deposits display a complex multilayered structure, unaffected by variations in wear protocol or bulk and surface chemistries. These deposits are predominantly composed of tear-derived lipids laid down in a well-defined fashion. The primary layer is composed of unsaturated lipids, whilst the secondary and tertiary layers are dominated by cholesterol and cholesterol esters. The composition and location of deposit components is unaffected by variations in, wear protocol, chemistry of the lens matrix, or tear composition of lens wearers. These findings suggest that unsaturated lipids are responsible for the biological interfacial conversion of hydrogel lenses, reducing their compatibility with the ocular environment.

Biocompatible Materials↗

Studies of the ocular compatibility of hydrogels. A review of the clinical manifestations of spoilation.

The range and nature of the various clinical manifestations of hydrogel contact lens spoilations are considered. An indication of the present view of the occurrence, chemical composition and potential aetiology for discrete elevated deposits, organic and inorganic surface films, plaques and granular deposits, microbial spoilation, lens discoloration and other extrinsic factors is provided. The literature is principally concerned with the clinical manifestations of spoilation and most observations have been made on lenses that have become so severely spoiled as to be unwearable. No serious attempt has yet been made to identify those tear species responsible for the development of the various types of deposits or of the effects of variations in the bulk and lens chemistry, and also wear protocols on the formation of deposits.

Adsorption↗

Studies of the ocular compatibility of hydrogels. White spot deposits--incidence of occurrence, location and gross morphology.

Light and scanning electron microscopical techniques have been employed to determine the morphology, geographical location and incidence of occurrence of discrete elevated deposits on a variety of commercial lenses of differing bulk and surface chemistries and also wear protocols. Spoilt lenses were derived from controlled lens wear trials and additional clinical sources. This type of elevated deposit displays a complex morphology and is composed of three distinctive yet interactive sub-layers. It is apparent that alterations in lens surface properties, wear protocol, and application of the device are not significant in determining deposit morphology. The rate of deposit formation is however, a function of the lens chemistry, wear protocol and the individual patient. These findings promote the belief that some common biological interface conversion event, or events, occur which reduce the biocompatibility of these materials with their ocular environment.

Biocompatible Materials↗

Polymers for biodegradable medical devices. II. Hydroxybutyrate-hydroxyvalerate copolymers: hydrolytic degradation studies.

The hydrolytic degradation of poly(hydroxybutyrate) together with a series of hydroxybutyrate-hydroxyvalerate copolymers has been studied. The effects of copolymer composition and molecular weight are presented together with the results of varying pH and temperature on the degradation rate. Degradation has been monitored by weight loss and water uptake measurements together with goniophotometric, surface energy and scanning electron microscopic studies. Some comparisons with the more widely used so-called 'biodegradable' polymers, poly(glycolic acid), poly(dioxanone) and the glycolic-lactic acid (90:10) copolymers are presented together with the effect of blood plasma on the degradation process.

Biocompatible Materials↗

Cellular interactions with synthetic polymer surfaces in culture.

The success of synthetic polymers as biomaterials depends upon their interfacial properties and resultant interactions with cells and biological fluids in vivo. A useful experimental approach to defining requirements for biocompatibility is to study the mechanisms by which synthetic substrata influence eukaryote cell behaviour in culture. Here we present an overview of the relationships between physical and chemical substratum properties and cell behaviour on a range of synthetic polymers. We relate our results to theories of in vivo tissue compatibility.

Animals↗

Requirements for cell spreading on polyHEMA coated culture substrates.

We have investigated the topography of polyHEMA coated culture substrates by scanning electron microscopy, and quantitatively assessed their effect upon the spreading activity of mammalian cells. Results indicate a clear correlation between cell spreading activity and polymer film discontinuity. Preparation of polyHEMA films on modified tissue culture substrates has allowed direct investigation of the role of the underlying substrate in regulating cell spreading, and confirms that apparent modulation of cell spreading by polyHEMA reflects increasing expression of the coated surface. We have further employed a spinning technique by which films of precise thickness, down to 0.01 micron, may be produced on coverslips. All polyHEMA coatings prepared in this way are smooth and complete. They do not allow cell attachment at any thickness. We conclude that polyHEMA is non-adhesive for mammalian cells.

Animals↗

Polymers for biodegradable medical devices XI. Microencapsulation studies: characterization of hydrocortisone-loaded poly-hydroxybutyrate-hydroxyvalerate microspheres.

Hydrocortisone-loaded monolithic microspheres were prepared, using a single emulsion solvent evaporation process, from a range of poly-beta-hydroxybutyrate-hydroxyvalerate copolymers in which both molecular weight and hydroxyvalerate content were varied. Many similarities were observed in the effects of process parameters and co-polymer composition on the morphologies of the microspheres, and the morphologies of microcapsules prepared (and previously reported) by a double emulsion process. The yields of the single emulsion process were generally superior to those of the double emulsion process, although these were adversely affected by hydrocortisone incorporation as the molecular weight of the copolymer was reduced. The predominant effect of hydrocortisone incorporation was on polymer morphology, characterized by the appearance of small surface pores; an effect which increased with increasing drug loading. Changes in polymer molecular weight, copolymer composition and process temperature, together with the incorporation of polycaprolactone in the form of a solvent blend, enabled microspheres with a range of morphologies to be produced providing the potential for control of drug release.

Absorbable Implants↗

Polymers for biodegradable medical devices. IX: Microencapsulation studies; effects of polymer composition and process parameters on poly-hydroxybutyrate-hydroxyvalerate microcapsule morphology.

Reservoir-type microcapsules were prepared using a double emulsion solvent evaporation technique from a series of nine different poly-beta-hydroxybutyrate (PHB)-based polymers in which both molecular weight and hydroxyvalerate content were varied. Particles prepared from a low molecular weight (MW 43,000) homopolymer had a shrivelled appearance, but were not porous. When the molecular weight of the fabricating homopolymer was increased to 540,000, however, these features disappeared and non-wrinkled particles with microporous surfaces were observed. Microcapsules prepared from a high molecular weight copolymer of PHB with 10.8 per cent hydroxyvalerate (HV) had a similar appearance, but particles prepared from a high molecular weight 20.1 per cent HV copolymer had much smoother and less porous surfaces. Lowering the molecular weight of the copolymer had the effect of producing particles that were generally distorted in shape and had highly irregular, macroporous, surface morphologies. Increasing the double emulsion temperature to 40 degrees C at 2 min after phase combination typically generated smoother and/or less porous particles and improved the batch yield. The numerous factors potentially responsible for the development of morphological characteristics of the products are discussed in the light of these observations.

Biodegradation, Environmental↗

Polymers for biodegradable medical devices. X. Microencapsulation studies: control of poly-hydroxybutyrate-hydroxyvalerate microcapsules porosity via polycaprolactone blending.

Reservoir-type microcapsules were prepared using a double emulsion solvent evaporation process from a range of different poly-beta-hydroxybutyrate homopolymers and copolymers thereof with 3-hydroxyvalerate (P(HB-HV) polymers) blended with 20 per cent by weight of poly-epsilon-caprolactone (PCL). Microcapsules prepared from these P(HB-HV)/20 per cent PCL blends had very different typical surface morphologies from those prepared from the corresponding unblended P(HB-HV) polymers. At this blend ratio the effects of polymer blending on particle morphology were clearly dependent on the molecular weight of P(HB-HV) polymer and, to a reduced extent, the 3-hydroxyvalerate content. Microcapsules were also prepared from blends of a high molecular weight P(HB-HV) polymer with PCL in which the proportion of the latter was varied from 0 to 100 per cent at 10 per cent intervals. Increasing the proportion of PCL from 0 to 50 per cent produced a systematic and dramatic increase in microcapsule porosity; with only skeletal particles being generated from the even 50-50 blend. When the proportion of PCL in the blends was increased from 50 to 70 per cent the level of particle porosity diminished, and at 80 per cent or above the microcapsules were essentially smooth and non-porous.

Biodegradation, Environmental↗