Cellular Response to Nanoparticles
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Cellular Response To Nanoparticles Sonya Shortkroff, MaryBeth Turell, Karen Rice and Thomas S. Thornhill Orthopaedic Research Laboratory Brigham and Women’s Hospital, Harvard Medical School Boston, MA 02115, U.S.A. ABSTRACT Particles of BaSO4 with sizes in nano-scale and micro-scale ranges were investigated for their interactions with fibroblasts in order to determine the biocompatibility of nano-sized particles. Cells were incubated in the presence of particles at 1, 10 and 100 times the particle to cell surface area ratio and at a single concentration of 0.138 mg/ml. Production by the fibroblasts of an inflammatory cytokine in response to the particles was measured and the effect of particle size and volume on cell viability was examined. All particles were cell associated and some agglomeration was visible at all size ranges. Release of interleukin-6 by cells subjected to the same concentration of Ba SO4 was similar to control levels, while addition of 1x surface area ratio (SAR) of particles to cells resulted in an increase in IL-6 from 94 pg/ml for 100 nm particles to 218 pg/ml with 2 µm particle diameter. By increasing particle to cell surface area ratios from 1x to 100x, cell viability was compromised for the 2µm particles but was not affected by the nanometer sized BaSO4 particles. INTRODUCTION Recent developments in nanotechnology have the potential to significantly impact the biomedical field. Nano-structured materials are being investigated as coatings and as composites for implantable materials. The unique properties conferred on these nanometer-sized particles and constructs may affect the cellular and tissue biocompatibility of the materials. A nano-composite of polymethylmethacrylate (PMMA)cement, in which a micrometer sized additive, BaSO4, was replaced with nanometer sized BaSO4 particles, has been developed for use with Orthopaedic implants. By addition of the smaller size particles and with the aid of a dispersing agent, a more uniform dispersion of BaSO4 within PMMA was achieved and, in addition, the fatigue properties of the cement were enhanced. Although soluble barium is toxic, BaSO4 is a relatively insoluble salt with a solubility in water of 2.5 µg/ml and, as such, is non-toxic and biocompatible[1]. As a radio-opaque agent, it has been added to bone cement, PMMA, in order to evaluate the stability of the implant radiographically. Although the bulk material is biocompatible, particles of PMMA containing BaSO4 have been shown to affect cellular responses in vitro. Lazarus, et al. demonstrated that PMMA particles containing BaSO4 produced higher levels of inflammatory cytokines than those without BaSO4 [2]and Sabokbar, et al. reported that the presence of BaSO4 in PMMA particles increased the bone resorptive activity of monocytes co-incubated with osteoblast-like cells[3]. An increase in the production and release of cytokines, such as tumor necrosis factor alpha (TNFα), interleukin-1 (IL-1) and interleukin-6 (IL-6), indicate an inflammatory response by cells to a foreign material [4-6]. Persis
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