The Glass Bone Matrix

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The sol-gel process inherently promotes nanoporosity, says Marques. To achieve interconnected macroporosity, Marques added a polymer to the sol-gel solution, causing a phase separation to occur parallel to the sol-to-gel transition.

The phase separation enabled Marques to overcome a simple law of thermodynamics, says Jain.

"Thermodynamically, the coexistence of nanopores and macropores is unstable in that the larger pores should absorb the smaller pores," he says. "But with Ana's help, we have developed a material that defeats that expectation."

After three months at Lehigh's IMI, Marques was able to produce glass with nanopores measuring 5 to 20 nm in diameter and macropores measuring more than 100 microns across. "The aim of our project was to create nano- and macroporosity in a bioactive material while achieving mechanical properties that match those of bone," says Marques.

"We believe our material will stimulate bone regeneration because cells will proliferate inside the scaffolding material and form tissues, thus facilitating the delivery of nutrients to regenerating bone tissue."

"When you attach the glass to the damaged bone," says Mohamed Ammar, a dentist and research scientist at the University of Alexandria's tissue-engineering lab, "a layer forms on the surface of the glass that has the same chemical composition as the natural bone. The bone cells come to this layer and attach to it, in effect, forming a bone matrix around the glass."

As the treated bone regenerates, says Marques, the scaffold, being biodegradable, is absorbed by the body."This is the next generation of biomedical applications," says Marques. "It will be helpful for all bones, ranging from teeth to arms and legs. It can be used for breaks, tumors and other defects."

"This kind of material," says Jain, "might have other applications, such as controlled drug delivery, which could be achieved when a drug is released at differing rates because of the varying porosity."

The scaffolding material, says Ammar, who is now helping Marei supervise in vivo tests in Egypt, offers new hope to his patients, many of whom are women suffering from osteoporosis.

"We've been giving our patients medicines and prescribing exercises to strengthen their bone tissue and slow down the disease," says Ammar, who recently concluded four months of research at Lehigh's IMI. "This gives us something new. It is personally very exciting."

Two techniques in a friendly duel
While the Lehigh IMI team is applying for a patent on its sol-gel technique, it is also testing a second technique for producing glass with dual porosity.

Ammar is conducting in vivo tests on both types of glass

The melt-quench technique, also called the melt-and-pour technique, is the traditional process for making glass, says Hassan Moawad, who leads a Lehigh group that is modifying the technique to achieve dually porous glass (see story, p. 13). Moawad is also a member of the materials science faculty at the University of Alexandria.

"This is a friendly competition between two groups," says Jain, "that will enable us to compare and contrast the efficiency of the two techniques."

The researchers in Moawad's group use standard glass-making techniques, weighing and mixing the oxide powders, melting them at 1500 degrees Celsius, then grinding and polishing the glass and cutting it into small discs. The heat treatment stimulates crystallization, which strengthens the glass. Researchers also use a chemical treatment to etch the glass and introduce desired porosity, x-ray diffraction to measure the degree of crystallization and hardness, and optical microscopy and SEM to characterize the glass.

The melt-quench technique produces a stronger, more solid glass than does the sol-gel process, says Moawad. Glass made with the melt-quench technique can also be more readily molded.

But glass made with the sol-gel technique appears to be more biocompatible than melt-quench glass, says Moawad.

Moawad's team has succeeded in producing glass that is porous at the nano- and macro-scales. They have used SEM to verify pore diameter and surface area, along with BET (Brunauer-Emmett-Teller), a technique that measures nanopore dimensions, and mercury porosimetry, which measures slightly larger pores.

Moawad spent a year optimizing the melt-quench mixture

A key to the team's success, says Moawad, was discovering the correct proportion of oxides in the glass powder mixture. Moawad worked one year to develop the most effective mixture of silicon, calcium, phosphorous and boron oxides.

The next step for the researchers, says Jain, is to investigate the mechanical properties and bioactivity of the new materials, as well as the responses of cells that interact with the material.

The Lehigh-Lisbon-Alexandria research team is working on these challenges with researchers from Princeton University through the U.S.-Africa Materials Institute, which is headquartered at Princeton and directed by Wole Soboyejo, a materials engineer at Princeton.

A graduate student from Senegal will come to Lehigh later in 2006 to work on the project, says Jain.