More than 1,000 tons (2.2 million pounds) of titanium devices are implanted in patients worldwide every year with joint replacements one of the more common procedures. Light, strong and totally biocompatible, titanium is one of the few materials that naturally match the requirements for implantation in the human body. Researchers have now developed an improved coating technique that could strengthen the connection between titanium joint-replacement implants with a patient’s own bone. The stronger connection – created by manipulating signals the body’s own cells use to encourage growth – could allow the implants to last longer.

Total knee and hip replacements typically last about 15 years until the components wear down or loosen. For many younger patients, this means a second surgery to replace the first artificial joint. With approximately 40 percent of the 712,000 total hip and knee replacements in the United States in 2004 performed on younger patients 45-64 years old, improving the lifetime of the titanium joints and creating a better connection with the bone becomes extremely important.

"Flower bouquet" clusters

Researchers at the Georgia Institute of Technology found that implants coated with “flower bouquet” clusters of an engineered protein that mimics the body’s own cell-adhesion material fibronectin made 50 percent more contact with the surrounding bone than implants coated with protein pairs or individual strands. The cluster-coated implants were fixed in place more than twice as securely as plugs made from bare titanium – which is how joints are currently attached.

The researchers believe the biologically-inspired material improves bone growth around the implant and strengthens the attachment and integration of the implant to the bone. This work also shows for the first time that biomaterials presenting biological sequences clustered together at the nanoscale enhance cell adhesion signals. These enhanced signals result in higher levels of bone cell differentiation in human stem cells and promote better integration of biomaterial implants into bone.

In this study, Georgia Tech School of Chemistry and Biochemistry professor David Collard and his students coated clinical-grade titanium with a high density of polymer strands – akin to the bristles on a toothbrush. Then, García and Tim Petrie – formerly a graduate student at Georgia Tech and currently a postdoctoral fellow at the University of Washington – modified the polymer to create three or five self-assembled tethered clusters of the engineered fibronectin, which contained the arginine-glycine-aspartic acid (RGD) sequence to which integrins binds.

Putting it to the test

To evaluate the in vivo performance of the coated titanium in bone healing, the researchers drilled two-millimeter circular holes into a rat’s tibia bone and pressed tiny clinical-grade titanium cylinders into the holes. The research team tested coatings that included individual strands, pairs, three-strand clusters and five-strand clusters of the engineered fibronectin protein.

Analysis of the bone-implant interface four weeks later revealed a 50 percent enhancement in the amount of contact between the bone and implants coated with three- or five-strand tethered clusters compared to implants coated with single strands. The experiments also revealed a 75 percent increase in the contact of the three- and five-strand clusters compared to the current clinical standard for replacement-joint implants, which is uncoated titanium.

The researchers also tested the fixation of the implants by measuring the amount of force required to pull the implants out of the bone. Implants coated with three- and five-strand tethered clusters of the engineered fibronectin fragment displayed 250 percent higher mechanical fixation over the individual strand and pairs coatings and a 400 percent improvement compared to the unmodified polymer coating. The three- and five-cluster coatings also exhibited a twofold enhancement in pullout strength compared to uncoated titanium.

Details of the new coating were reported in the August 18 issue of the journal Science Translational Medicine.