ABSTRACT
Aseptic loosening due to peri-prosthetic osteolysis is one of the primary causes for failure of artificial joint replacements. Implant-derived wear particles, often ultra-high molecular weight polyethylene (UHMWPE) microparticles, initiate an inflammatory cascade upon phagocytosis by macrophages, which leads to osteoclast recruitment and activation, ultimately resulting in osteolysis. Investigation into integrin receptors, involved in cellular interactions with biomaterial-adsorbed adhesive proteins, is of interest to understand and modulate inflammatory processes. In this work, we investigate the role of macrophage integrins Mac-1 and RGD-binding integrins in response to UHMWPE wear particles. Using integrin knockout mice as well as integrin blocking techniques, reduction in macrophage phagocytosis and inflammatory cytokine secretion is demonstrated when these receptors are either absent or blocked. Along this line, various opsonizing proteins are shown to differentially modulate microparticle uptake and macrophage secretion of inflammatory cytokines. Furthermore, using a calvarial osteolysis model it is demonstrated that both Mac-1 integrin and RGD-binding integrins modulate the particle induced osteolysis response to UHMWPE microparticles, with a 40% decrease in the area of osteolysis by the absence or blocking of these integrins, in vivo. Altogether, these findings indicate Mac-1 and RGD-binding integrins are involved in macrophage-directed inflammatory responses to UHMWPE and may serve as therapeutic targets to mitigate wear particle induced peri-prosthetic osteolysis for improved performance of implanted joints.
Subject(s)
Biocompatible Materials/toxicity , Integrins/immunology , Joint Prosthesis/adverse effects , Macrophages/immunology , Osteolysis/chemically induced , Osteolysis/immunology , Polyethylenes/toxicity , Animals , Cell Line , Female , Macrophage Activation/drug effects , Macrophage Activation/immunology , Macrophages/drug effects , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Nanoparticles/toxicity , Osteolysis/pathology , Particle Size , Prosthesis FailureABSTRACT
Thermoplastics have been increasingly used for fabricating microfluidic devices because of their low cost, mechanical/biocompatible attributes, and well-established manufacturing processes. However, there is sometimes a need to integrate such a device with components made from other materials such as polydimethylsiloxane (PDMS). Bonding thermoplastics with PDMS to produce hybrid devices is not straightforward. We have reported our method to modify the surface property of a cyclic olefin copolymer (COC) substrate by using corona discharge and grafting polymerization of 3-(trimethoxysilyl)propyl methacrylate; the modified surface enabled strong bonding of COC with PDMS. In this paper, we report our studies on the surface modification mechanism using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and contact angle measurement. Using this bonding method, we fabricated a three-layer (COC/PDMS/COC) hybrid device consisting of elastomer-based valve arrays. The microvalve operation was confirmed through the displacement of a dye solution in a fluidic channel when the elastomer membrane was pneumatically actuated. Valve-enabled microfluidic handling was demonstrated.
