One of the drawbacks to hip and knee replacements is that particulate wear debris is released by the grinding action of the implant surfaces, which can cause restricted mobility, pain, and even implant failure. While larger pieces of debris tend to be isolated by fibrous tissue, smaller pieces may create severe inflammation and discomfort. In many cases, the surgery needs to be redone.
One solution to this problem is coating the articulating surfaces of joint implants with harder materials, such as diamond, to improve wear resistance and reduce the number and size of debris particles that are released into the bloodstream and human tissue. Studies have shown that metal-on-metal hip implants result in fewer and smaller debris particles compared to plastic implant materials. Other research has revealed that smaller-sized metal-wear particles are also less likely to cause inflammation and osteolysis (bone reduction).
Scientists and bioengineers are now exploring the possibility of using nanostructured diamond coatings to improve the smoothness of the joint surface, reduce the amount of wear debris, and increase the longevity of implants. However, little is known about how nanodiamond wear material affects macrophages, immune cells that typically “defend against” debris particles by secreting chemicals that cause pain and inflammation. Intense macrophage activity can erode bone near the implant, creating instability, pain, and ultimately joint failure.
To learn more about the effects of nanodiamond wear debris on immune system response, researchers at the University of Alabama-Birmingham (UAB) studied how macrophages respond to various sizes and concentrations of nanodiamond wear particles. Their encouraging results were recently published in a 2012 paper in Acta Biomaterialia.
Studies have shown that metal-on-metal hip implants result in fewer debris particles compared to plastic implant materials. Image: UAB.edu
The research team, led by Vinoy Thomas, research assistant professor of materials science and engineering at UAB, investigated the effect of the size of synthetic nanodiamond particles on macrophage proliferation, apoptosis, metabolic activity, and inflammatory cytokine production. Macrophages were exposed to varying sizes (6, 60, 100, 250 and 500 nm) and concentrations (0, 10, 50, 100 and 30 200 lg ml-1) of synthetic nanodiamond particles. The particles were characterized by spectroscopic and microscopic techniques including XRD, Raman, IR, and TEM. Cell proliferation, viability, and morphology, as well as the responses of genes involved in wear-mediated inflammation, were determined.
“We observed that cell proliferation, but not metabolic activity, was decreased with nanoparticle sizes of 6-100 nm at lower concentrations (50 lg ml-1),” says Thomas. “Both proliferation and metabolic activity were significantly reduced with nanodiamond concentrations of 200 lg ml-1. Flow cytometry indicated a significant reduction in cell viability due to necrosis irrespective of particle size.”
In addition, nanodiamond exposure significantly reduced the expression of several genes that play key roles in inflammation and related bone loss, including tumor necrosis factor and platelet derived growth factor (PDGF). This can be explained by the low-key” response of macrophages to the nanodiamond debris, which would result in less inflammation and less activation of harmful genes.
In short, the effect of nanodiamond particle size on macrophage response as determined by analyses of cell proliferation, cell viability and cell morphology, apoptosis and phagocytosis (TEM imaging), and genetic expression of pro-inflammatory cytokines and chemokines suggests no potential inflammations due to a size effect (ranging from 6 to 500 nm) of diamond wear particles at low concentrations (650 lgml-1).
“These results add to the early evidence that nanodiamonds are indeed nontoxic in living cells,” says Thomas. “The next step will be to conduct experiments to confirm where nanodiamond particles of varying sizes and concentrations end up, and if buildup at those destinations is safe.”
“Past studies on diamond-joint surfaces have shown a marked reduction in wear-debris volume compared to first-generation alloy and polyethylene joint parts,” adds Yogesh Vohra, director of the UAB Center for Nanoscale Materials and Biointegration and senior author for the study. “We hope the reduced wear volume and particle size expected for diamond articulation will represent a major advance over conventional orthopedic bearings.”
Mark Crawford is an independent writer.
Our results add to the early evidence that nanodiamonds are indeed nontoxic in living cells.
Vinoy Thomas, Assistant Professor, UAB
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