AVS2011 Session BI-ThM: Biomedical Materials

A biomaterial is defined as “any synthetic material or device–e.g. implant or prosthesis-intended to treat, enhance or replace an aging or malfunctioning native tissue, organ or function in the body” David Williams, states that “Biocompatibility is largely about the chemical interactions that take place between the materials and the body fluids, and the physiological responses to these reactions.” These reactions are dominated by the initial events at the molecular level, the interface, thus it is not hard to see the relationship between the implant surface properties and it's in vivo. It is clear that the performance of a biomaterial is directly linked to the surface chemistry, composition and topography of the device. However, despite the preponderance of evidence, biomedical device companies as a whole do not utilize surafce analytical methods nearly enough. Why is that?

In orthopaedics, most of the implants are fabricated from metals which directly contact biological fluids that are typically complex aqueous mixtures. Consequently corrosion and/or corrosion prevention are important considerations in device manufacturing. For the most part, orthopaedics manufacturers utilize the same passivation methodologies used to impart corrosion resistance to stainless materials. Numerous researchers have characterized the impact of acid passivation on stainless materials, but little has been done to study the effect of these treatments on the CoCr alloys. One of the topics in this presentation deals with the effects of passivation on CoCr alloys. Specifically, the presentation will correlate specific surface treatments with surface chemistry and ultimately to metal ion release. The study will also address questions relating to the use of Citric acid as a green replacement for nitric acid passivation. There is no argument that the process is much greener, but there are plenty of questions as to its effectiveness. Considering that the “changes” imparted by the passivation solutions effect the outer most 10-100A, the only means to characterize the affects of passivation requires surface analysis methodologies. The importance of surface analysis methods, especially XPS, will be highlighted by this example.

In addition to the discussion of metal alloy passivation, this presentation will also deal with other surface related issues that could impact the biocompatibility of biomaterials. The talk will show the potential impact of packaging materials and cleaning processes on the surface chemistry and composition of biomaterials.

Controlled release of active pharmaceutical molecules from biocompatible polymers over defined time periods is an area of intense study. Present applications include drug eluting stents and other drug delivery systems. One of the most important parameters which govern drug dosing is the drug concentration depth profile in the supporting polymer matrix. In a previous study we have shown that combining X-ray photoelectron spectroscopy (XPS) with a coronene ion source is a very powerful tool for investigating the drug distribution with depth of a model system [1].

The use of cluster ion sources for sputter depth profiling of thin film or multilayer organic materials during XPS analysis has become routine. A wide range of organic systems are amenable to profiling and there is a good understanding of the experimental parameters which contribute to successful analysis. Here we report on extending the aforementioned study to materials which closely resemble real world samples intended for use in vivo.

Monoclonal antibodies are a notable and rising class of cancer therapeutics due to their enhanced targeting and immune system stimulation properties. Dosage guidelines are typically developed with many uncertainties which may affect treatment outcome and cause unwanted side effects. The requirement for an assay that can quickly and precisely measure the concentration of the monoclonal antibody in a serum sample of a patient during therapy is needed. The present study has demonstrated that the key to detection is compensation for variation in non-specific binding of serum to the assay surface. A microparticle-based assay with peptide antigen mimetics has been developed to rapidly determine the concentration of antibody drug present in serum specimens with high sensitivity. Alemtuzumab (anti-CD52) and rituximab (anti-CD20) antigen peptides, as discovered by phage display, were synthesized on 10 um TentaGel resin beads using conventional solid phase peptide synthesis techniques. The microparticle beads were modified to allow for multiplexing and microfluidic handling via fluorescent labeling and magnetic functionalization. The antigen-displaying fluoromagnetic particles were incubated with spiked serum samples which allowed free antibody to be captured. Primary antibody detection was performed on alemtuzumab while rituximab detection was used to compensate for non-specific serum binding to the beads. After washing, the beads were incubated with a fluorescently tagged secondary antibody for detection by flow cytometry. Serum from thirty (30) individual donors with various spiked serum concentrations of antibody drug were assessed using this assay. Analysis of bead fluorescence data allows for a limit of quantitation down to 0.5ug/ml of serum antibody drug concentration. Using detection of an antibody known to be absent in serum, an accurate compensation technique for non-specific binding has been developed on multifunctional antibody assay beads in realistic samples. The developed assay is robust against donor serum variation.