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In vivo biocompatibility testing of peek polymer for a spinal implant system: a study in rabbits.

We are developing a new spinal implant system (SIS) without fusion (bone graft). This SIS is made from two materials, metal and polyetheretherketone (PEEK) polymer. The Food and Drug Administration recommended testing in vivo, in an animal model, whether the PEEK polymer could be used in a SIS without any harm of wear debris to the nervous tissue (spinal cord and nerve roots). The objective was to evaluate the biological response of the spinal cord and nerve roots (dura mater) to PEEK polymer particles. Twenty-four female New Zealand white rabbits were used. The rabbits were divided into three groups: test (n = 12), control (n = 9), and sham (n = 3). During the surgery, the test group received the PEEK particle injections (5 x 10(7) particles per site, lumbar and thoracic), while the control group received only the vehicle (0.9% saline solution). The sham group had the same surgical approach without injection. In each group, the rabbits were euthanized at 1, 4, and 12 weeks postsurgery. The macroscopic and semiquantitative histologic analyses of the spinal cords (dura mater) showed normal vascularization and particle adherence to the connective tissue especially at the injection sites. Neither necrosis nor swelling of the dura mater and nerve roots was observed. The PEEK polymer is harmless to the spinal cord; thus it might be used as component in the spinal implant system.

Animals↗

In vitro biocompatibility of polyetheretherketone and polysulfone composites.

Short carbon fiber reinforced composites could potentially replace some of the metal alloys used in orthopedic implants. In particular, polysulfone and, more recently, polyetheretherketone have been considered as the matrix material for carbon fiber reinforced composite implant materials. ASTM standards F813 and F619 for direct contact cell culture evaluation and extraction were employed to determine the in vitro biocompatibility of a carbon fiber composite of polyetheretherketone, PEEK, in comparison to a carbon fiber reinforced polysulfone composite. The cell cultures were assessed qualitatively by microscopy and quantitatively using an enzyme assay to determine cytotoxicity. Overall, the cellular response to the PEEK and polysulfone composites were negligible indicating that further in vivo studies with these materials are appropriate.

Animals↗

Biological response to chopped-carbon-fiber-reinforced peek.

Polymer composites are being recognized as important implant materials for fracture fixation plates. The use of a composite material is dependent upon the mechanical properties of the material and its biocompatibility. The primary objective of this project was to evaluate 30% chopped-carbon-fiber-reinforced poly(etheretherketone) (CFRPEEK) as a potential material for use as a fracture fixation plate. A two-phase study was conducted. The first phase analyzed the short-term biocompatibility of CFRPEEK through rabbit muscle implant testing. CFRPEEK exhibited a nonspecific foreign body tissue reaction similar to the response observed with ultra-high-molecular-weight polyethylene (UHMWPE). In the second phase, four-hole CFRPEEK plates were implanted as internal fixation devices for transverse midshaft femoral osteotomies in beagles. The plates were effective in promoting fracture healing. A nonspecific foreign body reaction was observed to the plates and to particulate debris.

Animals↗

Long-term durability of the interface in FRP composites after exposure to simulated physiologic saline environments.

Fiber/matrix interfacial bond strength significantly influences the mechanical behavior of fiber-reinforced polymer (FRP) composites. Interfacial bond strength durability is therefore particularly important in the development of FRP composites for implant applications where diffused moisture may potentially weaken the material over time. In this study, the long-term durability of interfacial bonding in carbon fiber/380 grade polyetheretherketone (C/PEEK) and carbon fiber/polysulfone (C/PSF) composites was investigated after exposure to hygrothermal environments. A single fiber pull-out test was used to quantitatively determine the ultimate bond strength (UBS) of the samples following exposure. Samples were tested at three temperatures (37, 65, and 95 degrees C) for six time periods (0-5000 h) and in two environments (dry and physiologic saline-immersed). A mathematical model based on nth order chemical reaction kinetics was applied to describe the long-term durability of the interface. The results of this study indicate that interfacial bond strengths in C/PSF and C/PEEK (380 grade) composites are significantly decreased by exposure to physiologic saline and are functions of both time and temperature. For each material, the kinetics of degradation analysis predicts further bond strength losses following initial saturation, which then stabilizes at temperature-dependent equilibrium bond strength levels.

Benzophenones↗

Grafting amine-terminated branched architectures from poly(L-lactide) film surfaces for improved cell attachment.

Poly(L-lactide) (PLL) has been used as a bioabsorbable material in the medical and pharmaceutical fields. The unmodified hydrophobic PLL surface generally has low cell affinity; thus, modification of PLL film surface properties is necessary to improve its use as a biomaterial. Our surface modification method involved the use of photografting and typical wet chemistry to create branched architectures containing amine functionalities on the periphery of the grafted layers. Amine (-NH2) groups were first introduced on the PLL film surface by photoinduced grafting of 4,4'-diaminobenzophenone and the grafted branched architectures were created by subsequent reactions with succinic acid and tris(2-aminoethyl) amine. The resulting film surface was analyzed using contact angle goniometry and X-ray photoelectron spectroscopy. MC3T3 fibroblasts were cultured on unmodified PLL film and PLL films grafted with the branched structures and the films were subsequently analyzed by optical microscopy. The contact angle goniometry results showed an initial decrease and subsequent plateau in the water contact angles for the PLL films with each successive generation of the branched architectures. The X-ray photoelectron spectroscopy data provided insight into the structure of the grafted layer and revealed an increase in the nitrogen content with each generation. Optical micrographs showed enhanced cell attachment and viability on the surface-modified PLL films.

Amines↗

Rapid screening and characterization of drug metabolites using a new quadrupole-linear ion trap mass spectrometer.

The application of a new hybrid RF/DC quadrupole-linear ion trap mass spectrometer to support drug metabolism and pharmacokinetic studies is described. The instrument is based on a quadrupole ion path and is capable of conventional tandem mass spectrometry (MS/MS) as well as several high-sensitivity ion trap MS scans using the final quadrupole as a linear ion trap. Several pharmaceutical compounds, including trocade, remikiren and tolcapone, were used to evaluate the capabilities of the system with positive and negative turbo ionspray, using either information-dependent data acquisition (IDA) or targeted analysis for the screening, identification and quantification of metabolites. Owing to the MS/MS in-space configuration, quadrupole-like CID spectra with ion trap sensitivity can be obtained without the classical low mass cutoff of 3D ion traps. The system also has MS(3) capability which allows fragmentation cascades to be followed. The combination of constant neutral loss or precursor ion scan with the enhanced product ion scan was found to be very selective for identifying metabolites at the picogram level in very complex matrices. Owing to the very high cycle time and, depending on the mass range, up to eight different MS experiments could be performed simultaneously without compromising chromatographic performance. Targeted product ion analysis was found to be complementary to IDA, in particular for very low concentrations. Comparable sensitivity was found in enhanced product ion scan and selected reaction monitoring modes. The instrument is particularly suitable for both qualitative and quantitative analysis.

Animals↗

Synthesis of various geometric and enantiomeric oxime O-(alpha- and beta-methylcholinyl) ethers as potential anticholinergic agents.

Various enantiomeric and geometric oxime O-(alpha- and beta-methylcholinyl) ethers were synthesized as potential anticholinergic agents. The synthesis, separation, resolution, and structural characterization of these compounds are reported. The first step of the synthetic pathway involved an oxime formation, with subsequent O-alkylation of the respective oxime with 2-chloro-N,N-dimethylpropylamine hydrochloride. The separation of the alpha- and beta-structural isomers utilized vacuum fractional distillation and/or column chromatography, and the resolution of the enantiomers was accomplished via the formation of tartrate diastereoisomers. A preliminary pharmacological evaluation for anticholinergic activity was conducted using a rat ileum assay. Structure-activity relationships, including some stereochemical properties and antimuscarinic activity, are discussed.

Animals↗