Carbon fiber reinforced polymers for implantable medical devices.

Carbon fibers reinforced polymers (CFRPs) are prolifically finding applications in the medical field, moving beyond the aerospace and automotive industries. Owing to its high strength-to-weight ratio, lightness and radiolucency, CFRP-based materials are emerging to replace traditional metal-based medical implants. Numerous types of polymers matrices can be incorporated with carbon fiber using various manufacturing methods, creating composites with distinct properties. Thus, prior to biomedical application, comprehensive evaluation of material properties, biocompatibility and safety are of paramount importance. In this study, we systematically evaluated a series of novel CFRPs, aiming at analyzing biocompatibility for future development into medical implants or implantable drug delivery systems. These CFRPs were produced either via Carbon Fiber-Sheet Molding Compound or Fused Deposition Modelling-based additive manufacturing. Unlike conventional methods, both fabrication processes afford high production rates in a time-and cost-effective manner. Importantly, they offer rapid prototyping and customization in view of personalized medical devices. Here, we investigate the physicochemical and surface properties, material mutagenicity or cytotoxicity of 20 CFRPs, inclusive of 2 surface finishes, as well as acute and sub-chronic toxicity in mice and rabbits, respectively. We demonstrate that despite moderate in vitro physicochemical and surface changes over time, most of the CFRPs were non-mutagenic and non-cytotoxic, as well as biocompatible in small animal models. Future work will entail extensive material assessment in the context of orthopedic applications such as evaluating potential for osseointegration, and a chronic toxicity study in a larger animal model, pigs.

The micronucleus assay as a biological dosimeter in hospital workers exposed to low doses of ionizing radiation.

The health risk associated with low levels of ionizing radiation is still a matter of debate. A number of factors, such as non-target effects, adaptive responses and low-dose hypersensitivity, affect the long-term outcome of low-dose exposures. Cytogenetic bio-dosimetry provides a measure of the absorbed dose, taking into account the individual radiation sensitivity. The aim of the present study is to evaluate the value of the micronucleus (MN) test as a bio-dosimeter in hospital workers exposed to low doses of ionizing radiation. Blood samples were obtained from 30 subjects selected among workers exposed to X- and gamma-radiation, and 30 controls matched for sex, age and smoking from the same hospital. Micronucleus frequencies were analyzed by use of the cytokinesis-block method. The MN frequency was compared among the groups considering the confounding factors and the length of employment. No increase in the number of bi-nucleated cells with MN (BNMN), but a significant increase in the number of mono-nucleated cells with micronuclei (MOMN) was observed in exposed subjects compared with the controls. The relationship between MN frequency and accumulated dose (mSv) was evaluated. The length of employment did not affect the extent of MN frequency, but an increase of BNMN and MOMN cells was observed based on the accumulated radiation dose. Our study shows the sensitivity of the MN test in the detection of cytogenetic effects of cumulative exposure levels, suggesting the potential usefulness of this assay in providing a biological index in medical surveillance programs.

Gene expression changes in medical workers exposed to radiation.

The use of nuclear resources for medical purposes causes considerable concern about occupational exposure. Nevertheless, little information is available regarding the effects of low-dose irradiations protracted over time. We used oligomicroarrays to identify the genes that are transcriptionally regulated by persistent exposure to extremely low doses of ionizing radiation in 28 exposed professionals (mean cumulative effective dose +/- SD, 19 +/- 38 mSv) compared with a matched sample of nonexposed subjects. We identified 256 modulated genes from peripheral blood mononuclear cells profiles, and the main biological processes we found were DNA packaging and mitochondrial electron transport NADH to ubiquinone. Next we investigated whether a different pattern existed when only 22 exposed subjects with accumulated doses >2.5 mSv, a threshold corresponding to the natural background radiation in Italy per year, and mean equal to 25 +/- 41 mSv were used. In addition to DNA packaging and NADH dehydrogenase function, the analysis of the higher-exposed subgroup revealed a significant modulation of ion homeostasis and programmed cell death as well. The changes in gene expression that we found suggest different mechanisms from those involved in high-dose studies that may help to define new biomarkers of radiation exposure for accumulated doses below 25 mSv.

[Occupational exposure to antineoplastic drugs in a hospital setting: biological and environmental monitoring]. / Esposizione professionale ad antiblastici in ospedale: monitoraggio biologico e ambientale.

OBJECTIVE: To estimate the occupational exposure of hospital personnel handling antineoplastics drugs using a highly sensitive and specific analitycal method in biological and environmental samples. DESIGN: To develop analitycal methods for the biological and environmental monitoring of more than one substance. SETTING: Five departments of the Policlinico Sant'Orsola-Malpighi (Bologna, Italy) involved in the preparation and administration of antineoplastic drugs. PARTICIPANTS: 50 nurses handling antineoplastics drugs. MAIN OUTCOME MEASURES: Evaluation of the occupational exposure of hospital personnel handling and administering anticancer drug cocktails. RESULTS: 19 of 50 subjects were positive to biological monitoring. Three were positive for MTX only, 11 for CP only and 5 subjects were positive for both. Urinary MTX levels ranged from 0.3 to 2.0 ppb, CP ranged fom 0.06 to 10.0 ppb. Wipe tests showed a higher contamination on the hoods working tray (where drugs are prepared), suggesting that the organization layout can affect the surface contamination level. Samples from each department resulted positive for at least one of three drugs. CONCLUSIONS: The analytical methods developed allow sensitive and specific determination of indicators of internal and external dose. Biological monitoring is of primary importance for assessing the real espoxure of hospital personnel during the preparation and administration of the drugs. Environmental monitoring stresses the importance to observe the Guidelines for standard operating procedures and the importance of protective disposables to reduce exposure and the associated health risk.

[Biomonitoring of nurses occupationally exposed to antineoplastic drugs: the IMEPA Project]. / Identificazione di marcatori specifici di esposizione professionale a farmaci antiblastici usati in polichemioterapia: Progetto IMEPA.

OBJECTIVE: To develop a multiple-endpoint monitoring system in order to assess and minimize long term risks in hospital nurses exposed to antiblastic drugs. DESIGN: Molecular epidemiology study. SETTING: S. Orsola-Malpighi Hospital in Bologna, Italy: nurses exposed to antiblastic drugs. PARTICIPANTS: 50 exposed subjects (8 males and 42 females) and 50 unexposed individuals (8 males and 42 females) matched for age and smoking habits. MAIN OUTCOME MEASURES: Urinary markers of exposure, Heat Shock Proteins (HSPs) 27, 70, 90, 110, immunologic biomarkers in peripheral blood lymphocytes: apoptosis, cell-cycle analysis G1-S-G, typization of Natural Killer cells (NK) and receptors micronuclei; frequency in peripheral blood lymphocytes and in exfoliated buccal mucosa cells; activation ofspecific oncogenes (bax, bcl2). RESULTS: 19/50 subjects showed urinary antiblastic drug levels (3 subjects MTX, 11 subjects CP, 5 subjects MTX and CP). No statistically significant differences were observed in all the considered biomarkers between the exposed and control groups. CONCLUSION: This biomonitoring study doesn't evidence any early significant effect associated to the exposure to antiblastic drugs.