Abstract
BackgroundWith the advancement of biomedical technology, artificial materials have been developed to replace diseased, damaged or nonfunctional body parts. Among such materials, ultra high molecular weight alkane or modified alkyl polymers have been extensively used in heart valves, stents, pacemakers, ear implants, as well as total joint replacement devices. Although much research has been undertaken to design the most non-reactive biologically inert polyethylene derivatives, strong inflammatory responses followed by rejection and failure of the implant have been noted.Methodology/Principal FindingsPurification of the alkane polymers from the site of inflammation revealed extensive “in vivo” oxidation as detected by fourier transformed infra-red spectroscopy. Herein, we report the novel observation that oxidized alkane polymers induced activation of TLR1/2 pathway as determined by ligand dependent changes in intrinsic tyrosine fluorescence intensity and NF-κΒ luciferase gene assays. Oxidized polymers were very effective in activating dendritic cells and inducing secretion of pro-inflammatory cytokines. Molecular docking of the oxidized alkanes designated ligand specificity and polymeric conformations fitting into the TLR1/2 binding grooves.Conclusion/SignificanceThis is the first report of a synthetic polymer activating immune responses through TLR binding.
Highlights
With the advancement of biomedical technology, artificial materials have been developed to replace diseased, damaged or nonfunctional body parts
These micron-size particles as well as low molecular weight alkane polymers are responsible for the initiation of an aseptic inflammatory response known as osteolysis [5,9],[2]
Micron size PE particles were periprosthetic tissue obtained from implant failure prosthesis. e and f) PE particles are visualized as black material indicated by red arrows. g and h) PE sub-micron particles, indicated by red arrows, phagocyted by local antigen presenting cells
Summary
With the advancement of biomedical technology, artificial materials have been developed to replace diseased, damaged or nonfunctional body parts Among such materials, ultra high molecular weight alkane or modified alkyl polymers have been extensively used in heart valves, stents, pacemakers, ear implants, as well as total joint replacement devices. Much research has been undertaken to design the most non-reactive biologically inert polyethylene derivatives, strong inflammatory responses followed by rejection and failure of the implant have been noted
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