New bioglass reduces risk of titanium implant failure

Material accelerates formation of bone tissue and prevents proliferation of bacteria on surface of dental and orthopedic prostheses.

By Elton Alisson

Agência FAPESP – Researchers in the Materials Engineering Department of the Federal University of São Carlos (UFSCar) in São Paulo State, Brazil, have developed a new glass material with bioactive properties (bioglass) that, when deposited on the surface of titanium dental and orthopedic implants, reduces the risk of cracking caused by bacterial infection and accelerates the bonding of these metal prostheses with bone tissue (osseointegration).

Developed at the Center for Research, Teaching, and Innovation in Glass (CEPIV), one of the Research, Innovation and Dissemination Centers (RIDCs) funded by FAPESP, both the new material and the implant-coating process have been patented and are attracting the interest of business enterprises in Brazil and abroad.

“Our in vivo tests [in animals] showed that the initial stage of osseointegration for dental implants coated with the new bioglass was up to one and a half times faster than it was for uncoated implants,” said Clever Ricardo Chinaglia, a postdoctoral fellow at UFSCar with a scholarship from FAPESP and a participant in the project.

According to Chinaglia, the new material, informally called F18, is made of silica, calcium, sodium, potassium, magnesium and phosphorus. Its properties include accelerating the formation of bone tissue (osteoinduction), controlling inflammation (anti-inflammatory action), and facilitating the formation of blood vessels (angiogenesis) in certain living organisms, including humans.

One of the main differences between F18 and 45S5, the world’s first bioglass, developed in the 1960s, as well as other bioactive vitreous materials developed later, is that F18 contains chemicals that prevent crystallization and make it bactericidal (capable of killing bacteria). Most of the currently available types of bioglass are bacteriostatic; i.e., they only prevent bacteria from growing and reproducing.

Because it does not crystallize easily, F18 can be produced in the form of long, flexible bioactive fibers as well as more complex three-dimensional shapes. According to the researchers, F18 is the basis for the world’s only bioglass fiber.

F18 can also be ground into microscopic particles of a few microns (thousandths of a millimeter) in size, or even less than a micron. The particles can be made to adhere to the surface of a titanium implant so that it is biofunctionalized, conferring bioactive functions found only in certain organisms, such as inducing the formation of bone tissue and blood vessels.

As the bioglass coating applied to a titanium implant dissolves, it releases ions that are important for osseointegration. The coating disappears completely after the initial stages of the process, which last between seven and ten days, Chinaglia explained.

In addition to accelerating osseointegration, the new material’s bactericidal properties protect the surface of the implant against the formation of biofilm, a complex structure (created by bacteria) that is difficult to control and treat. As a result, Chinaglia said, the environment around the implant becomes free of these microorganisms.

“Bacterial infection can change pH, temperature and healing conditions, impairing osseointegration. Hence the importance of a bactericidal agent in the early stages,” Chinaglia told Agência FAPESP.

Biofunctionalization

To deposit particles of the new bioglass and biofunctionalize the coated implants, the researchers also created a technique whereby the particles are initially dispersed in a specially prepared gel. An implant is then coated with the gel so as to create a surface with a predetermined particle size and distribution.

When heated by different methods, the particles flow without crystallizing and adhere to targeted regions of the implant’s surface.

“The coating process creates a discontinuous layer on the surface of the implant, forming tiny islands of bioglass,” Chinaglia said, “so some areas are coated by bioglass, while others are not.”

The coated areas help to form new bone tissue and prevent bacteria from adhering to the implant during the early stages of osseointegration.

“The particles of bioglass we’ve developed are more soluble than 45S5 and other types of bioglass. They begin dissolving as soon as the implant is inserted and are totally dissolved by the end of the osseointegration process,” he said. “This also avoids problems of instability at the interface between the metal and the ceramic material, which is the most common cause of failure in implants coated with hydroxyapatite,” a synthetic calcium phosphate that resembles bone mineral.

Titanium and glass have different mechanical and thermal properties and hence are usually incompatible. This incompatibility explains why attempts to combine them in dental and orthopedic implants have failed in recent decades, according to Chinaglia.

“The attempt made 20 years ago to coat dental implants with a layer of hydroxyapatite failed for this reason, which is also why there are no metal implants coated with ceramic material to facilitate osseointegration on the market today,” he said.

“We tested titanium dental implants biofunctionalized with bioglass in animals and found no trace of the material on their surfaces after osseointegration, showing that the material is totally resorbed.”

Histomorphometric analysis shows that bone tissue forms on coated implants in two weeks, which is one and a half times faster than when uncoated implants are used. Bone histomorphometry measures the amount of bone and its cellular activity.

Commercialization

The researchers now plan to begin clinical trials in humans. Four firms – two based in the United States and two in Brazil – are interested in the technology and willing to fund its commercialization. The researchers have set up Vetra, a spinoff company that owns the patents on the new material and coating technique.

According to Chinaglia, Vetra will coat dental and orthopedic implants produced by specialized firms. “Under the business model we propose, it will supply not the end-product but the bioglass and the implant-coating process.”

The researchers also anticipate that fibers obtained from the new bioglass can be employed in membranes used by dental surgeons for bone regeneration and graft scaffolding.

“Many processing possibilities that haven’t been considered hitherto are opened up by the composition of this new bioglass and its non-crystallization,” said Edgar Dutra Zanotto, a professor of materials science and engineering at UFSCar and director of CEPIV.

Another product developed and patented by the researchers is a highly porous bone graft scaffold.

“The most widely used scaffold currently available in the marketplace is inorganic, made of hydroxyapatite particles. A scaffold made of bioglass, alone or in conjunction with other materials, would be much more effective in the process of tissue regeneration,” Chinaglia said. Chinaglia was a speaker at the recent colloquium “Research Excellence in a Globalized world: Experiences and Challenges from a Brazilian-German Perspective,” hosted on February 26-28 by the Alexander von Humboldt Foundation in São Paulo.

This was one of two major colloquia planned to be held outside Germany by the Bonn-based foundation in 2015. The other will takes place in November in South Korea.