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Biomedical subjects

A W Lloyd

Publications and source records attributed to A W Lloyd.

At least 19 recordsLinked to original sources
PubMed2006

Polyurethane/poly(hydroxyethyl methacrylate) semi-interpenetrating polymer networks for biomedical applications.

The thermodynamic miscibility, morphology, phase distribution, mechanical properties, surface properties, water sorption, bacterial adhesion and cytotoxicity of semi-interpenetrating polymer networks (semi-IPNs) based on crosslinked polyurethane (PU) and poly(hydroxyethylmethacrylate) (PHEMA) were studied to give an insight into their structure and properties. The free energies of mixing of the two polymers in semi-IPNs have been determined and it was shown that the values are positive and depend on the amount of PHEMA. This demonstrates that the components are immiscible, the extent of which is dependent upon variations in composition. The morphology of the semi-IPNs was analyzed with scanning electron microscopy and tapping mode atomic force microscopy (TMAFM). The micrographs of the semi-IPNs and TMAFM phase images indicated that distinct phase separation at the nanometer scale is observed. The mechanical properties reflect the changes in structure of semi-IPNs with composition. The stress at break increases from 3.4 MPa to 23.9 MPa, and the Young's modulus from 12.7 MPa up to 658.5 MPa with increasing amounts of PHEMA, but strain at break has a maximum at 40.4% PHEMA. The bacterial adhesion and cytotoxicity data suggest that semi-IPNs with PHEMA content above 22% may be used for biomedical material applications.

Absorbable Implants↗
PubMed2006

In vivo assessment of the osteointegrative potential of phosphatidylserine-based coatings.

The successful implantation of titanium-based implants for orthopaedic and dental applications is often hindered because of their mobility, which arises because of a lack of direct binding of the metal surface to the mineral phase of the surrounding bone. Ceramic coatings, although ensuring the integration of the implant within the tissue, are unstable and carry risks of delamination and of failure. Recently, a novel biomimetic approach has been developed where porous titanium implants are coated with calcium-binding phospholipids able to catalyse the nucleation of discrete apatite crystals after only 30 min incubation in simulated body fluids. The present work assesses the osteointegrative potential of this new class of coatings in an in vivo rabbit model and compares its performance with those of bare porous titanium and hydroxyapatite-coated titanium. The data obtained show that phosphatidylserine-based coatings, whilst resorbing, drive the growing bone into apposition with the metal surface. This is in contrast to the case of bare titanium.

Animals↗
PubMed2005

Bacterial adhesion to bisphosphonate coated hydroxyapatite.

Staphylococcus aureus (S. aureus) is commonly associated with microbial infection of orthopaedic implants. Such infections often lead to osteomyelitis, which may result in failure of the implant due to localised bone destruction. Bacterial adhesion and subsequent colonisation of the device may occur as a consequence of contamination during surgery, or by seeding from a distant site through the blood circulation. Coating of the hydroxyapatite (HA) ceramic component of artificial hip joints with the bisphosphonates clodronate (C) and pamidronate (P) has been proposed as a means to minimise osteolysis and thereby prevent loosening of the implant. However, the effect of the bisphosphonate coating on bacterial adhesion to the HA materials must be determined before this approach can be implemented. In this study coated HA materials were incubated with the S. aureus and the number of adherent bacteria determined using the Modified Vortex Device (MVD) method. The number of bacteria adherent to the P coated HA material was significantly greater than that adherent to uncoated HA (60-fold increase) or to the C coated HA (90-fold increase). Therefore, even though earlier studies suggested that P bound to HA may improve osseointegration, the results presented would suggest that the use of this coating may be limited by the potential increased susceptibility of the coated device to infection.

Bacterial Adhesion↗
PubMed2005

Bacterial adhesion to phosphorylcholine-based polymers with varying cationic charge and the effect of heparin pre-adsorption.

The steady increase in the use of medical implants and the associated rise of medical device infections has fuelled the need for the production of biomaterials with improved biocompatibility. 2-(methacryloyloxyethyl phosphorylcholine) (MPC) based coatings have been used to improve the biocompatibility of a number of different medical devices. Recent studies have investigated the use of a phosphorylcholine modified with cationic charge to encourage specific bio-interaction. Until now the affect of cationic charge incorporation in MPC copolymers on bacterial adhesion has not been investigated. This study attempts to address this by investigating the affect of charge on four different strains of bacteria commonly associated with medical device infections. In addition, the affect of pre-incubating these MPC-copolymers in heparin is also evaluated as this has previously been shown to improve biocompatibility and reduce bacterial adhesion. Bacterial adhesion was assessed by ATP bioluminescence and Scanning Electron Microscopy (SEM). Results suggest that bacterial adhesion generally increased with increasing cationic charge. When samples were however, pre-incubated with heparin a significant reduction in bacterial adhesion to the MPC-based samples was observed. The heparin remained bound and effective at reducing bacterial adhesion to the cationic MPC-based samples even after three weeks incubation in PBS. To conclude, the MPC-based cationic polymer coatings complexed with heparin may provide a promising solution to reduce medical device related infections.

Absorption↗
PubMed2004

Structural characteristics of activated carbons and ibuprofen adsorption affected by bovine serum albumin.

Structural characteristics of a series of MAST carbons were studied using scanning electron microscopy images and the nitrogen adsorption isotherms analyzed with several models of pores and different adsorption equations. A developed model of pores as a mixture of gaps between spherical nanoparticles and slitlike pores was found appropriate for MAST carbons. Adsorption of ibuprofen [2-(4-isobutylphenyl)propionic acid] on activated carbons possessing different pore size distributions in protein-free and bovine serum albumin (BSA)-containing aqueous solutions reveals the importance of the contribution of mesopores to the total porosity of adsorbents. The influence of the mesoporosity increases when considering the removal of the drug from the protein-containing solution. Cellulose-coated microporous carbon Norit RBX adsorbs significantly smaller amounts of ibuprofen than uncoated micro/mesoporous MAST carbons whose adsorption capability increases with increasing mesoporosity and specific surface area, burnoff dependent variable. A similar effect of broad pores is observed on adsorption of fibrinogen on the same carbons. Analysis of the ibuprofen adsorption data using Langmuir and D'Arcy-Watt equations as the kernel of the Fredholm integral equation shows that the nonuniformity of ibuprofen adsorption complexes diminishes with the presence of BSA. This effect may be explained by a partial adsorption of ibuprofen onto protein molecules immobilized on carbon particles and blocking of a portion of narrow pores.

Adsorption↗
PubMed2004

Effects of plasma irradiation on the wettability and dissolution of compacts of griseofulvin.

In this study, the use of plasma irradiation was investigated as a possible technique for increasing the dissolution rate of the poorly soluble drug griseofulvin. Plasma is a partially ionised gas consisting of ions, electrons and neutral species. Oxygen plasma was used to treat griseofulvin compacts as this would lead to the formation of oxygen containing functional groups on the surface of the compact thus increasing the wettability. Compacts containing 300 mg of the drug were prepared using a stainless steel punch and die assembly and plasma treated. The effect of the length and power of the plasma treatment upon the dissolution rate of griseofulvin was investigated. Dissolution experiments of griseofulvin were carried out using the paddle method using 0.1 M HCl and 0.1 M HCl with 2% sodium dodecyl sulphate (SDS) as the dissolution media. The wettability was assessed by contact angle measurements using the sessile drop technique with the contact angle being measured every second for a period of ten seconds using pure water (to European Pharmacopoeia standards). Plasma treated and untreated samples were also analysed by scanning electron microscopy. Although plasma treatment was found to increase the wettability of griseofulvin it was not found to increase the dissolution rate as the treatment caused surface fusion of the material.

Antifungal Agents↗
PubMed2004

Factors inducing in-stent restenosis: an in-vitro model.

In-stent restenosis is caused by the proliferation of the smooth muscle cells (SMCs) following a host response towards the implanted device. However, the precise biochemical and cellular mechanisms are still not completely understood. In this paper, the behaviour of SMCs has been investigated by an in vitro model where the cells were stimulated by platelet derived growth factor (PDGF) on tissue-like substrates as well as on biomaterials such as stainless steel (St) and diamond-like carbon (DLC)-coated St. The results demonstrated that SMCs have a completely different adhesion mode on St and become particularly prone to proliferation and pro-inflammatory cytokine secretion under PDGF stimulus. This would suggest that restenosis may caused by the accidental contact of the SMC with the St substrate under an inflammatory insult.

Carbon↗
PubMed2003

Controlled biological response on blends of a phosphorylcholine-based copolymer with poly(butyl methacrylate).

Phosphorylcholine (PC)-based polymers have been used in a variety of medical device applications to improve biocompatibility. Here, solutions containing poly(butyl methacrylate) (PBMA) and 2-methacryloyloxyethyl phosphorylcholine-co-lauryl methacrylate (MPC-co-LMA(2)) copolymer were spin-coated onto glass coverslips at various ratios ranging from 5:1 to 1:0 for each of the two components, respectively. The resulting blend coatings were shown to be phase-separated on the nanometre-scale by atomic force microscopy, the PC copolymer within the blend being preferentially expressed at the surface. The adsorption of two key blood proteins, fibrinogen and albumin were investigated using surface plasmon resonance as an indicator of biocompatibility. The adsorption of protein to a biomaterials' surface can then stimulate further biological responses. This study therefore, also investigates the materials ability to elicit an inflammatory response by studying the adhesion of human mononuclear cells to the material surface. The materials ability to support the adhesion and growth of other tissue cells was also evaluated, looking specifically at the adhesion and proliferation of rabbit corneal epithelial cells. Results suggest that the adsorption of proteins and the adhesion of both corneal epithelial cells and mononuclear cells are dependent on the composition of the PBMA:MPC-co-LMA(2) copolymer.

Adsorption↗
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↗
PubMed2003

Effects of oxygen plasma treatment on the surface wettability and dissolution of furosemide compacts.

The plasma irradiation of furosemide (frusemide) was investigated as a possible technique for increasing the dissolution rate of this drug. Oxygen plasma was used to generate oxygen-containing functional groups on the surface of the compact to increase the wettability of the surface and the dissolution rate of the drug. Compacts of furosemide (300 mg) were produced using a stainless steel die and punch assembly, which was placed into a KBr press. The time of the plasma treatment was varied to assess the effect if any upon the dissolution rate and the wettability of the drug. Dissolution experiments of the plasma-treated and untreated compacts were carried out using the paddle apparatus method. Dissolution was carried out at 37 degrees C using 1 L of 0.1 M HCl and phosphate buffer (pH 6). The wettability was assessed by contact angle measurements using the sessile drop technique. Untreated and plasma-treated samples were analysed by scanning electron microscopy at x 5000 magnification. Plasma treatment was found to lower the equilibrium contact angle from approximately 50 to 35 degrees but the dissolution rate was not significantly affected. This was attributed to fusion of the surface by the plasma treatment.

Diuretics↗
PubMed2002

The interactions of bisphosphonates in solution and as coatings on hydroxyapatite with osteoblasts.

Aseptic loosening is one of the major causes of failure of artificial hip joints, and it can occur for several reasons, including osteolysis of the bone tissue in response to stress shielding or cellular reactions to wear debris. Any treatment of the prosthesis which could minimize the osteolytic response of bone tissue may be able to extend the life-time of the implant. Bisphosphonates are potent inhibitors of osteoclastic bone resorption, and they bind avidly to hydroxyapatite (HA). Coating the prostheses with bisphosphonates may therefore inhibit osteolysis. We have investigated the potential for this approach by determining whether bisphosphonates interact with osteoblasts in vitro. The effects of pamidronate (P), clodronate (C), and etidronate (E) in solution and when coated onto HA were investigated. P inhibited protein and collagen syntheses potently when in solution, but not after being bound to HA. When bound to HA, both P and C increased DNA, protein and collagen syntheses of osteoblasts and may encourage the osseointegration of implants. The pharmacological effects of the bisphosphonates studied altered dramatically after binding to HA. This must be fully investigated before this approach to prolonging prostheses stability can be evaluated.

Journal Article↗
PubMed2001

Does MMP-2 expression and secretion change with increasing serial passage of keratocytes in culture?

The effects of ageing on matrix metalloprotease degradation of the extracellular matrix during corneal wound healing are largely unknown. The following study used an in vitro model of ageing to assess changes in MMP-2 RNA expression and protein secretion. Early passage (EP) EK1.BR keratocyte cultures from 14 to 18 cumulative population doublings (cpds) and late passage (LP) cultures from 40 to 47 cpds were used to isolate protein and mRNA samples. Total protein from EP and LP cultures was measured using the Bradford protein assay. Zymographic analysis of EP and LP samples was carried out to compare MMP-2 activity. Northern blot analysis was used to assess changes in MMP-2 mRNA expression by EP and LP cultures, using a digoxigenin (DIG) based chemiluminescent detection system. LP cultures secreted more total protein per cell. MMP-2 but not MMP-9 activity was detected in keratocyte cultures. Densitometric analysis of zymograms and calculation of MMP-2 activity indicated a significant increase in MMP-2 activity per cell (P<0.05, n=11). No difference was observed in the levels of MMP-2 mRNA expressed by EP and LP cultures. An increase in MMP-2 activity per cell by LP cultures suggests that senescent keratocytes increase their degradative capacity. Similar changes in the keratocyte phenotype within the ageing cornea may alter the balanced response necessary for adequate wound healing and may have implications for the therapeutic use of MMP inhibitors in the eye.

Cell Division↗
PubMed2001

Ocular biomaterials and implants.

The maintenance of vision is a key determinant of healthy ageing. This has been facilitated over recent decades by the development of a wide range of implants and biomedical devices to correct the functional deficiencies of disease, age and ocular trauma. This brief overview provides an insight into the structure of this unique organ, the major physiological functions of the component tissues and the present state of the art with respect to modern ocular implants. The review focuses primarily on the existing limitations of existing ocular biomaterials used in the fabrication of contact lenses, intraocular lenses, glaucoma filtration implants, keratoprostheses, intracorneal implants, scleral buckles and viscoelastic replacement agents. The challenge of improving ocular compatibility and ensuring the longevity of indwelling ocular devices is addressed along with the need to improve the physicochemical and mechanical properties of existing ocular biomaterials.

Animals↗
PubMed2001

A comparison of the use of an ATP-based bioluminescent assay and image analysis for the assessment of bacterial adhesion to standard HEMA and biomimetic soft contact lenses.

The aim of this study was to investigate in vitro adhesion of clinically relevant bacteria to standard HEMA and novel biomimetic soft contact lenses (SCL) using bioluminescent ATP assay and image analysis. Unworn SCL were incubated with Pseudomonas aeruginosa, Staphylococcus epidermidis or Serratia marcescens suspended in sterile phosphate buffered saline (PBS). The level of bacterial adhesion after 1, 2, 4, 6 and 18h, was assessed using both image analysis and a bioluminescent ATP assay. Species differences in the overall level of adhesion to the different types of lens were observed using both measurement techniques. Generally bacterial adhesion was shown to peak at 4-6 h, then decline to a much lower level by 18 h. After 4 h, adhesion of all species of bacteria to the biomimetic SCL (omafilcon A) was found to be significantly lower than to the standard HEMA SCL (polymacon) (p<0.05. Student's t-test, n = 4). Both these techniques demonstrated that novel biomimetic SCL materials exhibit significantly lower bacterial adhesion in vitro compared to standard HEMA SCL materials. SCL manufactured with these novel biomimetic materials may reduce the risk of infection.

Adenosine Triphosphate↗
PubMed2001

Volume--activated chloride currents in HeLa cells are blocked by tamoxifen but not by a membrane impermeant quaternary analogue.

BACKGROUND/AIMS: Tamoxifen has been shown to inhibit volume activated chloride currents in many cell types. Tamoxifen has also been reported to inhibit a number of cation channels as well as cytosolic proteins such as calmodulin. The mechanism of channel block by tamoxifen is not known but three hypotheses can be proposed: i) a direct effect following binding to the channel protein from the aqueous environment or ii) a direct effect on the channel protein after partitioning into the lipid membrane or iii) an indirect mechanism via binding to intracellular regulatory proteins after diffusion across the lipid membrane. The aim of these experiments was to distinguish between these hypotheses using membrane permeant and impermeant antioestrogens. METHODS: Volume activated chloride currents were recorded from single HeLa cells using whole cell patch clamp technique. The ability of tamoxifen and its membrane impermeant quaternary derivative ethyl bromide tamoxifen (EBT) to inhibit these currents was examined. RESULTS: Extracellular tamoxifen at 3 microM inhibited volume activated chloride currents in HeLa cells whereas EBT had no effect up to 10 microM when applied either to the extracellular bathing solution or the intracellular solution via the patch pipette. CONCLUSION: Eliminating the ability of tamoxifen to cross the plasma membrane abolishes its channel blocking activity against volume activated chloride channels in HeLa cells.

Chloride Channels↗
PubMed2000

Human keratocyte migration into collagen gels declines with in vitro ageing.

Although senescence in various cell types has been shown to have detrimental effects on wound repair, the effect of this phenomenon on corneal function with increasing age has yet to be elucidated. This study investigated the effect of in vitro ageing on keratocyte migration into a collagen gel matrix. The keratocyte cell strain EK1. BR was cultured to late passage and a comparison of early passage migration with that of late passage migration was carried out. Early or late passage keratocytes were seeded onto 6 collagen gels (1.75 mg ml(-1)) for each experiment. Gels were incubated at 37 degrees C for 72 h, stained with calcein AM (0.5 mg ml(-1)) and assayed for cell migration using fluorescent microscopy. Changes in the effect of EGF on keratocyte migration with age were assessed by the addition of EGF (20 ng ml(-1)) to 3 of the 6 gels in each experiment. Proliferative lifespan was measured by immunocytochemical detection of Ki67 activity. This study shows for the first time that keratocyte migration, and migration in response to EGF stimulation, significantly declines with increasing age of keratocytes in culture (P<0.001). As keratocyte migration in response to cytokine stimulation is vital for corneal repair, the accumulation of senescent keratocytes with age may impair corneal wound healing.

Cell Line↗
PubMed2000

Synthesis and bacterial degradation of an azopolymer.

Azopolymers were synthesised with differing degrees of hydrophobicity, from 2-hydroxyethylmethacrylate (HEMA), styrene and 2,2'-dimethylacryloyloxyazobenzene as azo crosslinker. Bacterial degradation of the series of polymers was assessed using a pure culture of the colonic organism Enterococcus faecalis and rat caecal contents. Polymer degradation was determined in terms of weight loss on polymer coated glass beads and using scanning electron microscopy after incubation. Similar weight loss occurred on incubation of polymers in both bacterial cultures and non-bacterial control. The presence of styrene was found to decrease the amount of weight loss. The polymer surfaces showed microscopic cracks and holes after incubation, again, this phenomenon was less pronounced with increasing styrene content. As there was no increase in polymer degradation in the presence of azo reducing microorganisms, the results of this study suggest that these polymers are degraded by mechanisms other than azo reduction.

Amaranth Dye↗