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March 21, 2012

Using titanium to induce bone differentiation and personalized implants

by Angela C.H. McDonald

Titanium can be found everywhere. It is used in cars, sporting equipment and even jewelry manufacturing. But did you know that titanium products are used inside the human body?

You may know someone who has undergone a joint replacement procedure or someone who has a dental implant. For decades, titanium alloys have been used as a biomaterial for these applications.

Titanium is a biocompatible material, which means that it is able to integrate into the body without being rejected. This is a major reason why titanium biomaterials are so popular in orthopedics and dentistry. However, the ability of a titanium implant to fuse with surrounding bone tissue inside the body (a property known as osseointegration) needs to be improved.

In addition to biocompatibility and osseointegration, the optimal bone implant should also recruit bone precursor cells within surrounding tissue and provide bioactive cues to induce proliferation and differentiation for new bone formation.

How can a bone implant be designed to provide instructive cues to its surrounding environment within the body?

 Researchers have made a number of modifications to titanium alloy implants to try to answer this question, including surface topography, oxide thickness, titanium alloy composition and bioactive surface coating.

The extracellular (i.e. outside the cell) space that exists within tissues can also provide instructive signals to cells. For example, the protein fibronectin, which exists in the extracellular space, can regulate cell adhesion and differentiation. Recently, researchers took advantage of this and attempted to recreate this ability on a titanium alloy surface. The report recently published in Biomaterials described the construction of extracellular matrix-like networks onto a titanium alloy using fibronectin and BMP2 (a growth factor that can direct bone differentiation) in a multi-layered biomaterial. The result: successful induction of osteogenesis and integration of the titanium implant into existing bone tissue.

The use of titanium implants was publicized heavily in the media last month when a Belgian company, called Layerwise, announced a jaw replacement surgery that took place in June 2011. A custom-made titanium jaw was implanted into an 83-year-old woman who suffered from a chronic bone condition that had left her jawbone nonfunctional. Following transplantation, functionality was restored.

Layerwise specializes in metal part manufacturing. The company employed 3D printer technology to create the custom implant. Prior to implant construction, MRI images of the woman’s face were used to determine the shape of the titanium jawbone. The titanium implant was coated with a ceramic compound and subsequently transplanted into the patient. While clinical data has not been released by Layerwise, the company reported that shortly after surgery, the patient was able to speak and swallow.

While researchers are making good headway in understanding the molecular and cellular responses to bone implants (and how these responses can be exploited to enhance bioactivity of implants), I think that taking advantage of commercial technology and forming partnerships with companies like Layerwise is what will really push us into the next generation of regenerative medicine and bone implants.



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