New Biomimetic Controlled-Release Capsules May Help in Gum Disease

McGowan Institute for Regenerative Medicine faculty are trying to open a new front in the battle against gum disease, the leading cause of tooth loss in adults and sometimes termed the most serious oral health problem of the 21st century.

“Our technology uses controlled-release capsules filled with a protein that would be injected in the pockets between the gums and the teeth,” said McGowan Institute for Regenerative Medicine faculty member Steven Little, PhD, chair of the Department of Chemical and Petroleum Engineering, associate professor, and Bicentennial Alumni Faculty Fellow of the University of Pittsburgh Swanson School of Engineering, who reported on the research at the 244th National Meeting & Exposition of the American Chemical Society.

“That’s ground-zero for periodontal disease ― ‘gum disease’ ― the place where bacteria breed and inflammation occurs. The capsules dissolve over time, releasing a protein that acts as a homing beacon. It guides immune cells to the diseased area, reducing inflammation, creating an environment that fights the disease process and even could create conditions favorable for gum tissue to regrow.”

Dr. Little and University of Pittsburgh colleagues including McGowan Institute for Regenerative Medicine faculty member Charles Sfeir, DDS, PhD, associate professor at Pitt’s Department of Oral Medicine and Pathology, have evidence from pre-clinical laboratory experiments that the approach does foster healing and regrowth of gum tissue damaged by periodontal disease.

A bacterial infection causes periodontal disease. It first appears as mild tenderness and bleeding of the gums. It leads to inflammation and, if left untreated, can damage the gums so that they recede and lose their attachment to the teeth. It may progress even further and damage bone and other tissues that hold teeth firmly in place. Surprisingly, gum disease has a number of deleterious effects outside the mouth, with some studies linking inflammation in the gums to an increased risk of heart disease, stroke, and preterm delivery in pregnant women.

Treatment includes scaling, root planing, and other procedures to remove the plaque and bacteria that have accumulated in pockets between the teeth and gums. Dentists may combine this with antibiotics to fight the bacteria involved in gum disease.

Many scientists are seeking alternative treatments that kill the bacteria. Dr. Little’s group is taking an entirely different approach. They are targeting the inflammation process. “Although bacteria start the disease, inflammation is what keeps it going and causes progressive damage,” Dr. Little explained.

To reduce inflammation at the gums, Dr. Little and colleagues designed injectable controlled-release capsules containing a protein encased inside a plastic-like polymer material. The polymer is already used in medicine in dissolvable sutures. After the capsules are injected, the polymer slowly breaks down, releasing the protein encapsulated inside. The protein, termed a chemokine, is already produced by the body’s existing cells in order to summon specialized white blood cells to a specific site. Scientists previously tried to keep those cells, termed lymphocytes, away from the gums so as to block inflammation from occurring in the first place.

“It seems counterintuitive to lure in a lymphocyte, which is traditionally thought of as an inflammatory cell, if there’s inflammation,” Dr. Little pointed out. “But remember that a certain level of natural inflammation is required to fight off an infection. Inflammation is inherently a good thing, but too much of it is a bad thing. That’s why we aim to restore the immune balance, or homeostasis.”

During the pre-clinical tests, Dr. Little’s team injected the capsules and discovered evidence that disease symptoms are dramatically reduced and that proteins and other substances involved in regrowth of gum tissue had appeared. Dr. Little said that this finding offers encouragement that the treatment could not only rebalance the immune system, but also prompt regrowth of lost gum and bone tissue in the mouth.

Illustration: Bone resorption of teeth. A new controlled-release system could treat and perhaps prevent bone resorption (shown here) in periodontal disease by balancing the local immune response to bacteria (Credit: Steven Little, PhD).