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Protein Nanoclusters Create Better Bonding Experience in Implants

Titanium implants coated with protein nanoclusters promote expedited osseointegration.

The question of how best to promote orthopedic implant integration with host tissue and bone has been at the center of a flurry of research-related activity in recent years. Scientists have achieved breakthroughs in functionally graded implant designs, novel surface-treatment methods, and smart coatings, for example. Taking a biological-based approach, however, researchers from the Georgia Institute of Technology (Georgia Tech; Atlanta) have developed a technique for coating titanium implants with protein nanoclusters to form strong, secure bonds with bone.

Biomimetic motifs made from engineered fibronectin are behind these strong bonds. The engineered protein serves as a ligand for extracellular matrix receptors called integrins that stimulate and enhance bone growth around the implant. "One key aspect that is often overlooked in this area is that in the normal function of these proteins, the cellular structures that interact with the proteins are fully active only when they're nanoclustered," explains Andrés García, a professor of mechanical engineering at Georgia Tech. "While people recognize this from a materials standpoint, it really has not been exploited. We set out to see whether the presentation of these biological motifs in this nanoclustered structure and orientation could enhance the integration of the device and how the cells respond to these surfaces."

Building on established protein sequences, the Georgia Tech researchers experimented with different self-assembled nanoscale clustering motifs. Effects of implant coatings with monomers, dimers, trimers, and pentamers of the integrin-targeted engineered protein were then evaluated.

"We found that when we presented these biological motifs in three or five copies, we had a significantly higher activity than when we presented a single copy or two copies," García notes. "Those levels were significantly higher than what you would see for normal [untreated] clinical-grade titanium." In vivo performance testing of the clusters in rat tibiae revealed a 250% increase in bone anchorage to the surrounding implant that was treated with multimer clusters compared with an implant surface coated with only single or double strands of proteins. Furthermore, the researchers report a 300% increase in activity in protein cluster-coated implants compared with untreated titanium implants.

This increased activity, according to the researchers, can be attributed to the nanoscale cluster construction, which amplifies the signal that is relayed by integrins. Increased implant-bone anchorage can consequently expedite patient recovery and yield stronger connections between natural bone and the implant, the latter of which can extend implant life and reduce or delay the need for revision surgeries. "This strategy has a biological target in terms of how it impacts the cells, so we expect [protein nanoclusters] to have a more-direct response and potentially a more-enhanced response," García adds.

Having demonstrated the efficacy of the protein nanoclusters in rats, the researchers plan next to test the coating method in a larger animal that may better represent the human condition, according to García. The scientists will likely also examine possible synergies between their nanoclusters and more-traditional approaches to implant integration, such as hydroxyapatite coatings. Together, these methods could potentially further enhance functional integration of implants and ultimately improve patient quality of life.

"Certainly there's still a lot of work that needs to be done. But down the line this may provide a simple strategy that is applicable to different types of materials to improve integration with the host tissues," García states. "While the majority of our emphasis has been on bone integration, we think that, because of the importance of the major class of proteins that we're studying, this will also have an impact for other devices."

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