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Biomaterials


largely on the implant’s surface properties. Through direct contact, the surface can influence how surrounding cells behave in ways that encourage bone growth. It must also have antibacterial properties to stave off infection, another common reason for implant failure that can also interfere with bone formation.


Thanks to studies done so far, some surface design elements that can be beneficial have been identified. For example, wettability allows cells to spread along the implant and more easily interact with it. Yet newer research has proposed surface modifications that could improve implant integration and survival to an even greater degree.


Altering surface microtopography Over the years, benchtop experiments have shown that if you constrain cells physically, for example by changing the physical topography of a material they’re in contact with, you can get them to do different things, says professor of Biomedical Engineering and Surgery at Northwestern University, Guillermo Ameer. For instance, you can get stem cells from bone marrow to differentiate into osteoblasts, which work to form bone. But prior to a landmark study published last June that Ameer was involved in, no-one had investigated the effects of micro-level implant surface modifications on bone growth in vivo without adding in any other factors to enhance tissue regeneration.


“Implants are getting better, the materials are getting better, but the infection rate is rising due to people getting older, more multidrug- resistant bacteria, and so on.”


Jessica Bertrand


The researchers, made up of an interdisciplinary team from Northwestern University and the University of Chicago, identified a particular pattern using micropillars that caused bone to form sooner compared to an implant with a flat surface in mice. “By basically squeezing the nucleus of the [stem] cell, we found that we could, just by pure physical means, alter how these cells are able to process their DNA in order to make more of a particular protein, or proteins,” Ameer explains. These proteins would “eventually tell the cell to become more bone-like or produce factors that would be more likely to induce bone formation”. Having an implant that speeds up osseointegration is significant because growing bone takes time: sometimes weeks or months. And until it’s integrated, micromovements between the bone and implant can affect how well it’s able to fix in place.


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“The faster you get the new tissue, the better off you’re going to be,” says Ameer.


Micropillar patterns could be combined with the current standard of creating roughness – forming pores in the implant surface that are visible to the human eye – to maximise effects on the bone. The bone interlocks with the implant as it grows into the pores, which has been found to both improve osseointegration and load bearing capacity. However, the surface within those pores is still smooth. Micropillars, which would affect a monolayer or bilayer of cells at most, can interact with cells that land on the implant surface, says Ameer. “Those cells will see another degree of patterning, besides the roughness.”


Preventing infection


An implant can have the most optimal properties for osseointegration possible, but if an infection develops, it’ll likely fail. “This is a huge problem in endoprosthesis nowadays,” says Professor Jessica Bertrand, head of the Experimental Orthopaedics Research Unit at the Orthopaedic University Hospital Magdeburg. “The implants are getting better, the materials are getting better, but the infection rate is rising due to people getting older, more multidrug-resistant bacteria, and so on.” Yet creating antibacterial implants is a twofold challenge: you need properties that keep infection at bay without interfering with the process of bone growth. In a paper published in January of this year, Bertrand and her colleagues found that an alloyed silver surface did both – and was more effective at repelling bacteria than a control titanium alloy. Titanium and its alloys are the most common materials used in orthopaedic implants. “We tested different silver concentrations to be antibacterial on one hand… and on the other hand, that still keeps the osteoblasts alive to form bone on the surface,” Bertrand explains. They found that Staphylococcus aureus, one of the main bacteria responsible for orthopaedic implant infections, attached to their silver surface significantly less than it did with the control. Better still, there was no negative effect on osteoblasts, suggesting that the surface wouldn’t impede bone growth. Interestingly, there was also drastically less formation of osteoclasts on the silver surface – cells that degrade bone – indicating that there would be increased bone formation. However, in vivo studies are needed to confirm this.


Antibacterial silver implants already on the market tend to work by releasing silver that is then taken up by bacteria. However, these particles can cause silver contamination, a condition that can turn the skin grey.


Medical Device Developments / www.nsmedicaldevices.com


Monstar StudioShutterstock.com


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