Characterization of Inflammatory and Fibrotic Encapsulation Responses of Implanted Materials with Bacterial Infection.

Medical device infections are costly, while preclinical assessment of antimicrobial properties for new materials is time intensive and imperfect at capturing the interrelated aspects of infection response and wound resolution. Herein, we developed an in vivo model for quantification of inflammatory and biocompatibility responses in the presence of a sustained implant-associated infection. The antimicrobial effectiveness of commercially available polymer materials was compared to that of thermoplastic polyurethane (TPU) materials modified with putative antimicrobial strategies as example test materials. Materials were incubated with bioluminescent Escherichia coli prior to implantation in a dorsal subcutaneous pocket in rats with an additional intraluminal bolus of bacteria. Infection kinetics were monitored with bioluminescence, and inflammatory infiltrate and fibrous capsule thickness were determined from stained histological sections. Our model resulted in a persistent infection, sensitive to antimicrobial effects, as the materials modified with a putative antimicrobial surface were able to significantly reduce the level of infection in animals at day 4 postimplantation with efficacy similar to that of commercially available antimicrobial drug-eluting polymers (positive controls). At day 30 postimplantation, the antimicrobial surface modified TPU tubing was found to promote complete elimination of intraluminal bacteria in the absence of antibiotics. Differences were also measurable in acute inflammation, as Wright-Giemsa staining demonstrated reduced inflammatory cell infiltration at day 4 postimplantation for antimicrobial TPU materials. Additionally, antimicrobial materials exhibited reduced fibrous capsule thickness coinciding with infection resolution, as compared to unmodified TPU controls. The developed model can be utilized for testing antimicrobial polymers in the context of a prolonged infection while also revealing concurrent differences in the infiltrating immune cell profiles and fibrous capsule thickness, thus improving the relevance of preclinical medical device material testing.

Optical limiting properties of nonlinear multimode waveguide arrays.

An experimental investigation of the transmission of multimode capillary waveguide arrays containing a liquid nonlinear absorber shows an enhanced nonlinear response relative to that found in a single waveguide and to the same length of bulk material. Comparison of the nonlinear response of arrays with different pitch to diameter (d/Lambda) ratios confirm that both the intensity distribution within an individual waveguide and coupling between the elements of the array influence the overall nonlinear response.

Surface modification of poly(ether urethane urea) with modified dehydroepiandrosterone for improved in vivo biostability.

In this study, a fatty acid urethane derivative of dehydroepiandrosterone (DHEA) was synthesized and evaluated as a polyurethane additive to increase long-term biostability. The modification was hypothesized to reduce the water solubility of the DHEA and physically anchor the additive in the polyurethane during implantation. Polyurethane film weight loss in water as a function of time was studied to determine the polymer retention of the modified DHEA. The polyurethane film with unmodified DHEA had significant weight loss in the first day (10%) that was previously correlated to rapid leaching of the additive. The polyurethane film with modified DHEA had significantly less weight loss at all time points indicating improved polymer retention. The effect of the modified DHEA additive on the biostability of a poly(ether urethane urea) was examined after 5 weeks of subcutaneous implantation in Sprague-Dawley rats. Optical micrographs and infrared analysis of the specimens indicated that the modified DHEA bloomed to the surface of the film forming a crystalline surface layer approximately 10-15 microns thick. After explantation, this surface layer was intact without measurable differences in surface chemistry as monitored by attenuated total reflectance-Fourier transform infrared spectroscopy. There was no evidence of degradation of the polyurethane underneath the modified DHEA surface layer as compared with the polyurethane control. We have concluded that the modified DHEA self-assembled into a protective surface coating that inhibited degradation of the polyurethane. The roughness of the modified DHEA surface layer prevented adherent cell analysis to determine if the additive retained the ability to down-regulate macrophage activity. Subsequent studies will investigate the ability of surface-modifying additives to modulate cellular respiratory bursts in addition to the formation of an impermeable barrier. This bimodal approach to improving biostability holds great promise in the field of polyurethane biomaterials.

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.

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 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.