Stability and biocompatibility studies of implantable materials using isothermal microcalorimetry

摘要

The objectives of this research were to investigate the feasibility of using isothermal microcalorimetry (IMC) to (1) predict the long-term storage stability of calcium sulfate implantable bone void filler, with and without added tobramycin sulfate antibiotic, (2) compare the physico-chemical stability of ultra-high molecular weight polyethylene (UHMWPE) reference materials and total joint components under simulated storage and implantation conditions, (3) in combination with other analytical (ESR and FTIR) and mechanical tests (MDBT) to determine the factors that most influence the long-term physico-chemical stability of UHMWPE implant components, and (4) study macrophage interactions with particulate debris derived from orthopaedic implant materials.;1. A new application of isothermal microcalorimetry (1MC) to measure the chemical stability of implant materials is described. Specifically, the "storage stability" of calcium sulfate (CaSO 4) pellets containing tobramycin sulfate (TS) was assessed. IMC heat flow rate measurements were obtained at three temperatures (30, 40, and 50°C), in air at 27% r.h.;2. Most total joint systems rely on ultra-high molecular weight polyethylene (UHMWPE) as one bearing surface and hard, polished metal, typically cobalt-chrome alloy, as the other. Different sterilization methods appear to affect the long-term mechanical properties and wear resistance of UHMWPE to varying degrees. There is substantial evidence that gamma radiation sterilization makes UHMWPE more susceptible to degradation than other methods, such as ethylene oxide or gas plasma sterilization. Differences in degradation rate (physico-chemical stability) can be detected by exothermic heat production. We utilized isothermal microcalorimetry (IMC) to evaluate UHMWPE heat production immediately after sterilization by various standard methods.;3. In this work, the correlation between UHWMPE physico-chemical stability and both sterilization method and the time of storage and/or implantation was investigated. Four. different test methods were employed---isothermal microcalorimetry (IMC), electron spin resonace (ESR), fourier-transformed infra-red spectroscopy (FTIR), and miniature disc bend test (MDBT)---to provide complementary information to develop a better understanding of the relationship between stability, sterilization methods, and shelf or implementation time. Each method was used to examine specimens obtained from shelf-stored or clinically retrieved UBMWE---tibial plateau inserts (TPIs) and reference grade rod-stock material.;4. A new in vitro method to gauge the metabolic heat response of macrophages (MO) to particulate materials similar to those shed from the surfaces of orthopaedic implant materials is described. Present thinking in orthopaedics suggests that this response involves the release of cytokines that stimulate osteoclastic action, and that this may result in peri-implant osteolysis. In some patients, osteolysis leads eventually to an unstable implant and the clinical necessity of revision surgery. Whereas the majority of work cited in the literature relies upon chemical analysis (e.g., ELISA assay) to periodically determine MO response to particles. here we use isothermal microcalorimetry (IMC) for direct continuous measurement of metabolic heat production to gauge the response. IMC is a screening method, in that it ensures (theoretically) that no energy-consuming phagocytic response goes undetected, and that the aggregate metabolic magnitude of the responses is determined. (Abstract shortened by UMI.).