As any dentist or physician will attest, sometimes a patient's body doesn't want to cooperate when it's time for a wound to heal. Frequently, a wound doesn't heal. At other times, a considerable period of time elapses.

With that in mind, a team of U-M School of Dentistry researchers began collaborating to try to answer a logical follow-up question to such predicaments. The question - Can anything be done to "speed things up" to help a patient?

The answer appears to be "yes."

Several years ago, Drs. William Giannobile and Peter Ma, along with their researchers, teamed up to try to discover an answer to the question.

Recently they publicized their discoveries which showed that, with some help, it might be possible for the body to control how quickly or how slowly replacement tissues grow so wounds heal. Their work may also lead to creating new blood vessels.

Although human applications are years away, it's possible the results of their research may one day be used for dental procedures, bone grafting, or tissue replacement to treat injuries. It might also help diabetics or elderly patients with wound healing problems.

Combining Expertise

Giannobile, a professor and periodontist, and Ma, a professor with appointments in dentistry and engineering, combined their expertise to investigate ways to control the growth rate for tissues and blood vessel replacement.

"As a clinical periodontist and biologist, I have been intrigued for a long time about how the body orchestrates a sequence of events that lead to healing caused by wounds or injuries," said Giannobile, who is the director of the Michigan Center for Oral Health Research. "Both Peter's background and experiences, and mine, led to what both of us thought was a natural cross-fertilization of ideas with a common goal, to help people with wounds that need healing."

Similar to adjusting a thermostat, their approach focuses on dialing up or dialing down how quickly growth factors can influence tissue growth or repair.

Ma's research has an engineering bent - developing new materials that have potential dental and medical applications. Some materials, such as restorative dental materials, are developed to directly replace the structure and function of damaged or diseased tissues and organs.

Mimicking Human Tissue Wound Healing

Some are developed as scaffolding (matrix materials) for cells to grow on and develop into new tissues. As new tissues develop, the special materials (scaffolds) degrade and are absorbed into the body, leading to "natural" tissue replacement and/or regeneration.

The Ma lab developed scaffolds with a unique nanofibrous 3-D network with designed pore structures from biodegradable polymers. These nanofibers mimic the structural proteins of human tissue at the nanometer scale and advantageously support tissue regeneration or wound healing.

In addition, the Ma lab developed nanosized spheres that can release biological molecules at individualized rates so that biological events can be orchestrated to tailor tissue and vascular regeneration.

"By loading platelet-derived growth factors into these nanospheres and then attaching them to a lattice-like nanofibrous scaffold, the growth factor was able to recruit cells that stimulate the body's own machinery that is responsible for healing," Ma said.

Varying Growth Factor Regeneration

As the tissue grows, it crawls into the scaffold, which eventually dissolves.

"Growth factor is typically dumped in and releases over a period of hours," said Giannobile. "With certain wounds you might want a lot (of growth factor) in the beginning, and with others you might want a little released over a longer period of time. We've basically found a way to dial up or dial down the release rate of these growth factors."

Platelet derived growth factor is FDA-approved for treatment of diabetic ulcers and to promote bone repair in tooth-associated defects, but time-release delivery has been a big problem. Ma said the one of the keys was finding a way to preserve the biological properties of the growth factor in the nanoparticle for controlled release.

"The molecular configuration we have developed is unique. No one else anywhere in the world is using it," Ma said. "But I do think it has the potential to be first used in dentistry in the oral cavity before it's used in an orthopedic setting. But my hope is that a broad range of applications can be found to use this discovery."

Giannobile said "this technology can be applied to humans, but it still has a ways to go before we use this approach." The next step is to evaluate a broader range of wounds, followed by early stage human studies, Giannobile said. The research is funded by the National Institutes of Health.

The work of Ma and Giannobile was featured in a paper, Nanofibrous Scaffolds Incorporating PDGF-BB Microspheres Induce Chemokine Expression and Tissue Neogenesis in Vivo. It's available online at the Public Library of Science, a nonprofit organization of scientists committed to making the world's scientific and medical literature freely accessible to scientists, patients, policy makers, and others. The URL is: www.plosone.org/article/info:doi/10.1371/journal.pone.0001729.

The University of Michigan School of Dentistry is one of the nation's leading dental schools engaged in oral health care education, research, patient care, and community service. General dental care clinics and specialty clinics providing advanced treatment enable the School to offer dental services and programs to patients throughout Michigan. Classroom and clinic instruction prepare future dentists, dental specialists, and dental hygienists for practice in private offices, hospitals, academia, and public agencies. Research seeks to discover and apply new knowledge that can help patients worldwide. For more information about the School of Dentistry, visit us on the Web at: www.dent.umich.edu.

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