Biomedical subjects

James M Anderson

Publications and source records attributed to James M Anderson.

At least 55 records · Page 3Linked to original sources

PubMed2004

Poly(carbonate urethane) and poly(ether urethane) biodegradation: in vivo studies.

Several strategies have been used to increase the biostability of medical-grade polyurethanes while maintaining biocompatibility and mechanical properties. One approach is to chemically modify or replace the susceptible soft segment. Currently, poly(carbonate urethanes) (PCUs) are being evaluated as a replacement of poly(ether urethanes) (PEUs) in medical devices because of the increased oxidative stability of the polycarbonate soft segment. Preliminary in vivo and in vitro studies have reported improved biostability of PCUs over PEUs. Although several studies have reported evidence of in vitro degradation of these new polyurethanes, there has been no evidence of significant in vivo degradation that validates a degradation mechanism. In this study, the effect of soft segment chemistry on the phase morphology, mechanical properties, and in vivo response of commercial-grade PEU and PCU elastomers was examined. Results from dynamic mechanical testing and infrared spectroscopy suggested that the phase separation was better in PCU as compared with PEU. In addition, the higher modulus and reduced ultimate elongation of PCU was attributed to the reduced flexibility of the polycarbonate soft segment. Following material characterization, the in vivo biostability and biocompatibility of PEU and PCU were studied using a subcutaneous cage implant protocol. The results from the cage implant study and cell culture experiments indicated that monocytes adhere, differentiate, and fuse to form foreign body giant cells on both polyurethanes. It is now generally accepted that the reactive oxygen species released by these adherent macrophages and foreign body giant cells initiate PEU biodegradation. Attenuated total reflectance-Fourier transform infrared analysis of explanted samples provided evidence of chain scission and crosslinking in both polyurethanes. This indicated that the PCU was also susceptible to biodegradation by agents released from adherent cells. These results reinforce the need to evaluate and understand the biodegradation mechanisms of PCUs.

Biocompatible Materials↗

PubMed2004

Effect of soft-segment chemistry on polyurethane biostability during in vitro fatigue loading.

The effect of soft-segment chemistry on biostability of polyurethane elastomers was studied with a diaphragm-type film specimen under conditions of static and dynamic loading. During testing, the films were exposed to an H(2)O(2)/CoCl(2) solution, which simulated the oxidative component of the in vivo environment. Films treated for up to 24 days were evaluated by IR spectroscopy and by optical and scanning electron microscopy. Biostability of a poly(ether urethane) (PEU), which is known to undergo oxidative degradation, was compared with biostability of a poly(carbonate urethane) (PCU), which is thought to be more resistant to oxidation than PEU. Materials similar to PEU and PCU, in which the polyether or polycarbonate soft segment was partially replaced with poly(dimethylsiloxane) (PDMS), were also tested with the expectation that PDMS would improve soft-segment biostability. Oxidative degradation of the polyether soft segment of PEU was manifest chemically as chain scission and cross-linking and physically as surface pitting. Biaxial fatigue accelerated chemical degradation of PEU and eventually caused brittle stress cracking. In comparison, the polycarbonate soft segment was more stable to oxidation; there was minimal chemical or physical degradation of PCU, even in biaxial fatigue. Partial substitution of the polyether soft segment with PDMS enhanced oxidative stability of PEU. Although both strategies for modifying soft-segment chemistry improved the resistance to oxidative degradation, the outstanding mechanical properties of PEU were compromised to some extent.

Biocompatible Materials↗

PubMed2004

In vivo inflammatory and wound healing effects of gold electrode voltammetry for MEMS micro-reservoir drug delivery device.

The in vivo biocompatibility and biofouling of gold electrodes for a microelectromechanical systems drug delivery device were investigated in a rodent model. The role of the applied voltage and gold electrolysis products in modulating the inflammatory response (biocompatibility), and the temporal adhesion of cellular populations onto macroscopic gold film electrodes (biofouling) were analyzed in reference to two controls, devices to which voltage was not applied (uncorroded) or voltage was applied to inert platinum electrodes (electrical controls). Voltammetry was applied to the gold surfaces once (day 4, 7, 14, 21, 28, 35, 42, or 49), while voltage of identical magnitude was applied to the electrical controls. An inflammatory response characterized by a rapid decrease of leukocyte concentration to control levels was observed 48 h following voltage application with no significant cell concentration difference (p > 0.05) between the corroded devices and electrical controls. The histological evaluation of the direct implant fibrous capsule showed comparable thickness of voltage applied and control specimens. The gold corrosion peak current showed no significant difference (p > 0.05) among peak values at all time points. It was concluded that gold electrode corrosion was biocompatible and its electrochemical performance was not hindered by fibrous capsule formation.

Animals↗

PubMed2004

Differential degradation rates in vivo and in vitro of biocompatible poly(lactic acid) and poly(glycolic acid) homo- and co-polymers for a polymeric drug-delivery microchip.

The biocompatibility and biodegradation rate of component materials are critical when designing a drug-delivery device. The degradation products and rate of degradation may play important roles in determining the local cellular response to the implanted material. In this study, we investigated the biocompatibility and relative biodegradation rates of PLA, PGA and two poly(lactic-co-glycolic acid) (PLGA) polymers of 50:50 mol ratio, thin-film component materials of a drug-delivery microchip developed in our laboratory. The in vivo biocompatibility and both in vivo and in vitro degradation of these materials were characterized using several techniques. Total leukocyte concentration measurements showed normal acute and chronic inflammatory responses to the PGA and low-molecular-weight PLGA that resolved by 21 days, while the normal inflammatory responses to the PLA and high-molecular-weight PLGA were resolved but at slower rates up to 21 days. These results were paralleled by thickness measurements of fibrous capsules surrounding the implants, which showed greater maturation of the capsules for the more rapidly degrading materials after 21 days, but less mature capsules of sustained thicknesses for the PLA and high-molecular-weight PLGA up to 49 days. Gel-permeation chromatography of residual polymer samples confirmed classification of the materials as rapidly or slowly degrading. These materials showed thinner fibrous capsules than have been reported for other materials by our laboratory and have suitable biocompatibility and biodegradation rates for an implantable drug-delivery device.

Biocompatible Materials↗

PubMed2004

Macrophage behavior on surface-modified polyurethanes.

Adherent macrophages and foreign body giant cells (FBGCs) are known to release degradative molecules that can be detrimental to the long-term biostability of polyurethanes. The modification of polyurethanes using surface modifying endgroups (SMEs) and/or the incorporation of silicone into the polyurethane soft segments may alter macrophage adhesion, fusion and apoptosis resulting in improved long-term biostability. An in vitro study of macrophage adhesion, fusion and apoptosis was performed on polyurethanes modified with fluorocarbon SMEs, polyethylene oxide (PEO) SMEs, or poly(dimethylsiloxane) (PDMS) co-soft segment and SMEs. The fluorocarbon SME and PEO SME modifications were shown to have no effect on macrophage adhesion and activity, while silicone modification had varied effects. Macrophages were capable of adapting to the surface and adhering in a similar manner to the silicone-modified and unmodified polyurethanes. In the absence of IL-4, macrophage fusion was comparable on the modified and unmodified polyurethanes, while macrophage apoptosis was promoted on the silicone modified surfaces. In contrast, when exposed to IL-4, a cytokine known to induce FBGC formation, silicone modification resulted in more macrophage fusion to form foreign body giant cells. In conclusion, fluorocarbon SME and PEO SME modification does not affect macrophage adhesion, fusion and apoptosis, while silicone modification is capable of mediating macrophage fusion and apoptosis. Silicone modification may be utilized to direct the fate of adherent macrophages towards FBGC formation or cell death through apoptosis.

Apoptosis↗

PubMed2004

The role of claudins in determining paracellular charge selectivity.

Tight junctions create regulated barriers in the paracellular space between epithelial cells, including those of the airway and alveolus. Junctions vary widely throughout the body in their electrical resistance and, to some extent, in their ionic charge selectivity. Paracellular differences complement transcellular transport to define overall water, ion, and solute movements. A large family of transmembrane proteins called claudins has recently been implicated in creating the variable properties of the junction. Here we highlight the evidence that claudins are functional components of the barrier. Supportive data include evidence from deletion of selected claudins in mice, human genetic diseases of claudins 14 and 16, and direct experimental tests of the hypothesis that the extracellular charged residues on claudins influence the passage of ions through the junction. Alterations in claudin expression profiles may contribute to epithelial lung dysfunction during infection and inflammation. Much work remains to be done in the molecular characterization of tight junctions in the lung in normal physiology and during pathologic processes.

Animals↗

PubMed2003

Reversal of charge selectivity in cation or anion-selective epithelial lines by expression of different claudins.

Tight junctions (TJ) regulate paracellular ionic charge selectivity and conductance across epithelial tissues and cell lines. These properties vary among epithelia, and recent evidence implicates the claudins, a family of TJ transmembrane proteins, as important determinants of both characteristics. To test the hypothesis that each claudin contributes a characteristic charge discrimination to the TJ, we expressed claudins-2, -4, -11, and -15 in both cation-selective Madin-Darby canine kidney (MDCK) II cells and in anion-selective LLC-PK1 cells and examined changes in transepithelial electrical resistance (TER) and paracellular charge selectivity. Regulated expression and localization were verified by immunoblot analysis and immunofluorescence microscopy, respectively. Expression of claudin-4 increased TER in both cell lines, whereas effects of the others on TER were variable. Claudin-4 and -11 decreased paracellular permeability for Na+ in MDCK II cells, whereas neither claudin-2 nor -15 had an effect. Conversely, in LLC-PK1 cells, claudin-2 and -15 increased the permeability for Na+, whereas claudin-4 and -11 were without effect. We conclude that the contribution of each claudin is most easily detectable when it reverses the direction of monolayer charge selectivity. These results are consistent with a model in which exogenous claudins add new charge-selective pores, leading to a physiological phenotype that combines endogenous and exogenous contributions. Additionally, it is possible to rationalize the direction of charge selectivity conferred by the individual claudins on the basis of electrostatic effects of the charged amino acids in their first extracellular loops.

Amino Acid Sequence↗

PubMed2003

Effect of strain and strain rate on fatigue-accelerated biodegradation of polyurethane.

A diaphragm-type film specimen was used to study in vitro degradation of poly(etherurethane urea) (PEUU) under conditions of dynamic loading. This geometry allowed both uniaxial and biaxial loading in a single experiment. During testing, the film was exposed to a H(2)O(2)/CoCl(2) solution that simulated in vivo oxidation of PEUU. The combination of dynamic loading and biaxial tensile strain accelerated oxidative degradation. The effects of biaxial strain magnitude and strain rate were examined separately by increasing the frequency of fatigue loading from 0 to 1 Hz with constant maximum biaxial strain and by changing the maximum biaxial strain while maintaining constant strain rate. In the ranges of biaxial strain energy (0.17 to 0.55 MPa) and strain rate (0 to 46% s(-1)) tested, the rate of degradation increased with increasing strain rate whereas strain magnitude had essentially no effect on degradation rate. Although loading conditions affected the rate of oxidative degradation, ATR-FTIR analysis suggested that in all cases the mechanism of degradation did not change. Chemical degradation produced a brittle crosslinked surface layer marked by dimpling and pitting, as observed with scanning electron microscopy. Pits served as stress concentrators and initiated environmental stress cracks under dynamic loading but not under static (creep) loading. Small pits were sufficient to initiate cracks at higher strain rates whereas only large pits initiated cracks at lower strain rates. Consequently, a higher strain rate produced more profuse cracking.

Biodegradation, Environmental↗

PubMed2003

Claudin 14 knockout mice, a model for autosomal recessive deafness DFNB29, are deaf due to cochlear hair cell degeneration.

Tight junctions (TJs) create ion-selective paracellular permeability barriers between extracellular compartments. In the organ of Corti of the inner ear, TJs of the reticular lamina separate K(+)-rich endolymph and Na(+)-rich perilymph. In humans, mutations of the gene encoding claudin 14 TJ protein cause profound deafness but the underlying pathogenesis is unknown. To explore the role of claudin 14 in the inner ear and in other tissues we created a mouse model by a targeted deletion of Cldn14. In the targeted allele a lacZ cassette is expressed under the Cldn14 promoter. In Cldn14-lacZ heterozygous mice beta-galactosidase activity was detected in cochlear inner and outer hair cells and supporting cells, in the collecting ducts of the kidney, and around the lobules of the liver. Cldn14-null mice have a normal endocochlear potential but are deaf due to rapid degeneration of cochlear outer hair cells, followed by slower degeneration of the inner hair cells, during the first 3 weeks of life. Monolayers of MDCK cells expressing claudin 14 show a 6-fold increase in the transepithelial electrical resistance by decreasing paracellular permeability for cations. In wild type mice, claudin 14 was immunolocalized at hair cell and supporting cell TJs. Our data suggest that the TJ complex at the apex of the reticular lamina requires claudin 14 as a cation-restrictive barrier to maintain the proper ionic composition of the fluid surrounding the basolateral surface of outer hair cells.

Animals↗

PubMed2003

Biodegradation of polyurethane under fatigue loading.

A method utilizing expansion of a diaphragm-type film specimen was developed to study in vitro biodegradation of poly(etherurethane urea) (PEUU) under conditions of dynamic loading (fatigue). A finite element model was used to describe the strain state, which ranged from uniaxial at the edges of the film to balanced biaxial tensile strain at the center. During testing, the film was exposed to a H(2)O(2)/CoCl(2) solution, which simulated in vivo oxidative biodegradation of PEUU. The extent of chemical degradation was determined by infrared analysis. Physical damage of the film surface was characterized by optical microscopy and scanning electron microscopy. Dynamic loading did not affect the rate of degradation relative to unstressed and constant stress (creep) controls in regions of the film that experienced primarily uniaxial fatigue; however, degradation was accelerated in regions that experienced balanced biaxial or almost balanced biaxial fatigue. It was concluded that the combination of dynamic loading and biaxial tensile strain accelerated oxidative degradation in this system. Chemical degradation produced a brittle surface layer that was marked by numerous pits and dimples. Physical damage of the surface in the form of cracking occurred only in fatigue experiments. Cracking was not observed in unstressed or creep tests. Cracks initiated at the dimples produced by chemical degradation, and propagated in a direction that was determined by the strain state.

Biocompatible Materials↗

PubMed2003

In vivo leukocyte cytokine mRNA responses to biomaterials are dependent on surface chemistry.

An in vivo mouse cage implant system was used to determine whether leukocyte cytokine mRNA responses to implanted biomaterials were dependent on surface chemistry. Surfaces displaying various chemistries (hydrophobic, hydrophilic, anionic, and cationic) were placed into stainless steel cages and implanted subcutaneously. Semiquantitative RT-PCR analyses revealed that hydrophilic surfaces showed a decreased expression of proinflammatory cytokines, IL-6 and IL-8, and pro-wound healing cytokines, IL-10 and TGF-beta by adherent cells, and mRNA levels of the proinflammatory cytokine, IL-1beta, and the pro-wound healing cytokine IL-13 were decreased in surrounding, exudate cells. Cytokine responses by adherent and exudate cells to hydrophobic, anionic and cationic surfaces were similar and indicative of a strong inflammatory response at the earliest time point followed by a wound healing response at later time points. However, no differences in the types or levels of exudate cells for any of the surfaces or the empty cage at each of the respective time points were observed, indicating their respective biocompatibility. These studies identify hydrophilic surface chemistries as having significant effects on leukocyte cytokine responses in vivo by decreasing the expression of inflammatory and wound healing cytokines by inflammatory cells adherent to the biomaterial as well as present in the surrounding exudate.

Animals↗

PubMed2003

Foreign body-type multinucleated giant cell formation is potently induced by alpha-tocopherol and prevented by the diacylglycerol kinase inhibitor R59022.

Multinucleated foreign body giant cells (FBGCs) form by monocyte-derived macrophage fusion on implanted biomedical devices and are believed to mediate oxidative damage to biomaterial surfaces. Our in vitro system of human macrophage culture and interleukin (IL)-4-induced FBGC formation was developed to study the macrophage fusion mechanism and the physiological significance of FBGCs on implanted biomaterials and at other sites of chronic inflammation. Here, we demonstrate that the antioxidant vitamin E (90% alpha-tocopherol) moderately induces macrophage fusion and increases IL-4-induced FBGC formation. Moreover, purified alpha-tocopherol, but not beta-, gamma-, or delta-tocopherol, most remarkably induces macrophage fusion, leading to cultures of confluent FBGCs below normal plasma concentrations. This is not observed with the similar antioxidants probucol or Trolox, suggesting that the alpha-tocopherol effects on FBGC formation are independent of its antioxidant activity. Consistent with the reported activation of diacylglycerol kinase by alpha-tocopherol, the diacylglycerol kinase inhibitor R59022 completely abrogates FBGC formation. R59022 inhibition of IL-4-induced FBGC formation is reversed by alpha-tocopherol, suggesting that FBGC formation involves diacylglycerol kinase activation. This study suggests a novel role for diacylglycerol kinase in the mechanism of macrophage fusion/FBGC formation at sites of chronic inflammation and reveals that the pleiotropic lipophilic compound, alpha-tocopherol, is a highly potent macrophage fusion factor.

Antioxidants↗

PubMed2003

Biocompatibility and biofouling of MEMS drug delivery devices.

The biocompatibility and biofouling of the microfabrication materials for a MEMS drug delivery device have been evaluated. The in vivo inflammatory and wound healing response of MEMS drug delivery component materials, metallic gold, silicon nitride, silicon dioxide, silicon, and SU-8(TM) photoresist, were evaluated using the cage implant system. Materials, placed into stainless-steel cages, were implanted subcutaneously in a rodent model. Exudates within the cage were sampled at 4, 7, 14, and 21 days, representative of the stages of the inflammatory response, and leukocyte concentrations (leukocytes/microl) were measured. Overall, the inflammatory responses elicited by these materials were not significantly different than those for the empty cage controls over the duration of the study. The material surface cell density (macrophages or foreign body giant cells, FBGCs), an indicator of in vivo biofouling, was determined by scanning electron microscopy of materials explanted at 4, 7, 14, and 21 days. The adherent cellular density of gold, silicon nitride, silicon dioxide, and SU-8(TM) were comparable and statistically less (p<0.05) than silicon. These analyses identified the MEMS component materials, gold, silicon nitride, silicon dioxide, SU-8(TM), and silicon as biocompatible, with gold, silicon nitride, silicon dioxide, and SU-8(TM) showing reduced biofouling.

Animals↗

PubMed2003

Effects of adsorbed heat labile serum proteins and fibrinogen on adhesion and apoptosis of monocytes/macrophages on biomaterials.

A previously established human monocyte culture protocol was used to determine the effects of varying adsorbed proteins on monocyte/macrophage adhesion and survival on dimethyl-silane (DM) or RGD modified glass coverslips. Cells were allowed to adhere for 2 h in the absence of protein or in the presence of serum, fibrinogen (Fg), heat inactivated serum (HIS), serum supplemented with Fg or HIS with Fg. Cell adhesion and apoptosis rates were determined on days 0 (2 h), 3, 7 and 10 of culture. The presence of serum alone in the initial culture was sufficient to optimize monocyte/macrophage adhesion and survival rates. Adding Fg to serum did not increase adhesion nor decrease apoptotic rates. No protein or the addition of HIS during the initial incubation period significantly decreased monocyte/macrophage adhesion and survival on both surfaces, however, the addition of Fg to HIS restored adhesion and survival rates to those seen with in the presence of serum alone on RGD surfaces. These studies demonstrate that monocyte/macrophage adhesion and survival on biomaterial surfaces are optimized by adsorbed heat labile serum proteins while adsorbed Fg plays a surface property-dependent role.

Journal Article↗

PubMed2003

Inhibition of bacterial and leukocyte adhesion under shear stress conditions by material surface chemistry.

Biomaterial-centered infections, initiated by bacterial adhesion, persist due to a compromised host immune response. Altering implant materials with surface modifying endgroups (SMEs) may enhance their biocompatibility by reducing bacterial and inflammatory cell adhesion. A rotating disc model, which generates shear stress within physiological ranges, was used to characterize adhesion of leukocytes and Staphylococcus epidermidis on polycarbonate-urethanes and polyetherurethanes modified with SMEs (polyethylene oxide, fluorocarbon and dimethylsiloxane) under dynamic flow conditions. Bacterial adhesion in the absence of serum was found to be mediated by shear stress and surface chemistry, with reduced adhesion exhibited on materials modified with polydimethylsiloxane and polyethylene oxide SMEs. In contrast, bacterial adhesion was enhanced on materials modified with fluorocarbon SMEs. In the presence of serum, bacterial adhesion was primarily neither material nor shear dependent. However, bacterial adhesion in serum was significantly reduced to < or = 10% compared to adhesion in serum-free media. Leukocyte adhesion in serum exhibited a shear dependency with increased adhesion occurring in regions exposed to lower shear-stress levels of < or = 7 dyne/cm2. Additionally, polydimethylsiloxane and polyethylene oxide SMEs reduced leukocyte adhesion on polyether-urethanes. In conclusion, these results suggest that surface chemistry and shear stress can mediate bacterial and cellular adhesion. Furthermore, materials modified with polyethylene oxide SMEs are capable of inhibiting bacterial adhesion, consequently minimizing the probability of biomaterial-centered infections.

Bacterial Adhesion↗

PubMed2002

Biomaterial adherent macrophage apoptosis is increased by hydrophilic and anionic substrates in vivo.

An in vivo rat cage implant system was used to identify potential surface chemistries that prevent failure of implanted biomedical devices and prostheses by limiting monocyte adhesion and macrophage fusion into foreign-body giant cells while inducing adherent-macrophage apoptosis. Hydrophobic, hydrophilic, anionic, and cationic surfaces were used for implantation. Analysis of the exudate surrounding the materials revealed no differences between surfaces in the types or levels of cells present. Conversely, the proportion of adherent cells undergoing apoptosis was increased significantly on anionic and hydrophilic surfaces (46 +/- 3.7 and 57 +/- 5.0%, respectively) when compared with the polyethylene terephthalate base surface. Additionally, hydrophilic and anionic substrates provided decreased rates of monocyte/macrophage adhesion and fusion. These studies demonstrate that biomaterial-adherent cells undergo material-dependent apoptosis in vivo, rendering potentially harmful macrophages nonfunctional while the surrounding environment of the implant remains unaffected.

Animals↗

PubMed2002

Recent advances in ion chromatography suppressor improve anion separation and detection.

The Alltech DS-Plus suppressor improves and simplifies anion analysis by suppressor-based ion chromatography (IC). In addition to suppressing the mobile phase and enhancing the analyte signal, the DS-Plus suppressor removes carbonic acid from the suppressor effluent when carbonate-hydrogencarbonate mobile phases are used, reducing the water dip that interferes with early eluting peaks, increasing detection sensitivity, and enabling carbonate-hydrogencarbonate gradients. The ability to operate with carbonate-hydrogencarbonate gradients places exceptional separating power in the mobile phase, forgoing the need for expensive columns with special selectivity. Continuous operation and solid-phase chemistry eliminates the need for external regenerants, switching valves, and multiple operating modes.

Anions↗

PubMed2002

Solving complex anion separation problems with a carbonate-hydrogencarbonate gradient.

This paper describes the application of a new suppressor to solve complex anion separation problems with carbonate-hydrogencarbonate gradients. In addition to suppressing the mobile phase and enhancing the analyte signal like any other ion chromatography suppressor, the new DS-Plus suppressor removes carbonic acid from the suppressor effluent when carbonate-hydrogencarbonate mobile phases are used. This greatly reduces the background signal, enabling carbonate-hydrogencarbonate gradients. Since carbonate-hydrogencarbonate mobile phase has stronger eluting power than hydroxide or tetraborate, only dilute concentrations are needed to separate most anions. By adjusting the carbonate-hydrogencarbonate ratio in the mobile phase, various anion mixtures including those containing organic and inorganic anions with -1 to -3 charges can be separated on one or two columns, eliminating the needs for columns with special selectivity.

Anions↗