Researchers at the Georgia Institute of Technology have developed an improved coating technique that could strengthen the connection between titanium joint-replacement implants and a patients' own bone (Science Translational Medicine, August 18, 2010).
The stronger connection -- created by manipulating signals the body's own cells use to encourage growth -- may allow the implants to last longer, according to the university.
For the study, Georgia Tech's School of Chemistry and Biochemistry professor David Collard, Ph.D., and his students coated clinical-grade titanium with a high density of polymer strands -- akin to the bristles on a toothbrush. They then modified the polymer to create three or five self-assembled tethered clusters of the engineered fibronectin, which contained the arginine-glycine-aspartic acid sequence to which integrins binds.
To evaluate the in vivo performance of the coated titanium in bone healing, the researchers drilled 2-mm circular holes into a rat's tibia bone and pressed tiny clinical-grade titanium cylinders into the holes. They tested coatings that included individual strands, pairs, three-strand clusters and five-strand clusters of the engineered fibronectin protein.
"To investigate the function of these surfaces in promoting bone growth, we quantified osseointegration," explained AndrĂ©s GarcĂa, Ph.D., a professor in Georgia Tech's Woodruff School of Mechanical Engineering and the Petit Institute for Bioengineering and Bioscience, in a press release.
Analysis of the bone-implant interface four weeks later revealed a 50% 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% 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.
"By clustering the engineered fibronectin pieces together, we were able to create an amplified signal for attracting integrins, receptors that attached to the fibronectin and directed and enhanced bone formation around the implant," Garcia said.
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% higher mechanical fixation over the individual strand and pairs coatings and a 400% 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.
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.
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