A new double-duty hydrogel attacks bacteria to treat bone infections and encourages regrowth with a single application.
Automobile accidents, combat wounds, cancer treatments, and other conditions may require surgery that can lead to difficult-to-treat bone infections that delay healing.
The injectable hydrogel, a network of cross-linked polymer chains, contains the enzyme lysostaphin and the bone-regenerating protein BMP-2. In a new study using a small animal model, researchers showed significant reduction in an infection caused by Staphylococcus aureus—a common infection in orthopedic surgery—along with regeneration within large bone defects.
“Treatment for bone infections now often requires two surgeries to both eliminate the infection and heal the injured bone,” says Andrés J. García, executive director of the Parker H. Petit Institute for Bioengineering & Bioscience at the Georgia Institute of Technology.
“Our idea was to develop a bifunctional material that does both things in a single step. That would be better for the patient, cost less, and reduce hospitalization time. We have shown that we can engineer the hydrogel to control the delivery and release of both the antimicrobial enzyme and the regenerative protein.”
The hydrogel-based therapy could be useful to treat established bone infections, and as a prophylactic during surgery to prevent infection.
Doctors often treat bone infections today with systemic antibiotics and surgery to clean the injury. If the infection occurs with implants, surgeons might need to remove them. Once the infection is gone, additional surgery may be required to implant proteins that stimulate bone regrowth and restore the implant. Also, dead bacteria can prompt a harmful inflammatory reaction.
Researchers chose lysostaphin, an enzyme that kills the bacteria by cleaving cell walls without generating inflammation. The enzyme keeps working within the hydrogel after it polymerizes.
“With this strategy, we can get rid of the bacteria in such a way that the body re-establishes a normal inflammatory environment that allows the bone to heal,” García says. “Use of lysostaphin has been limited by poor stability inside the body, but in the gel, it can maintain stability for at least two weeks. That allows for controlled release over a longer period of time, which is sufficient for what we are trying to do.”
Beyond treating infections, the new technique might be used to prevent infection during surgery. For instance, if doctors insert a screw to repair an injury, they might apply the hydrogel to the screw threads. The soft gel would not affect the repair.
The next step in the research would be to repeat the study in large animals, after which researchers could consider clinical trials if the material proves promising.
“The mechanisms used to fight off infection depends on the species,” Garcia says. “That’s why it’s so important to repeat the studies in a large animal after testing in mice or rats. Showing efficacy in a large animal model would be a key step toward human trials.”
The hydrogel material has been used in the human body before, and researchers designed it to quickly leave the treatment site.
“The hydrogel breaks down into small building blocks that are excreted in the urine,” Garcia says. “After several weeks, there is no synthetic material left in the body and it is replaced by normal healing tissue.”
The National Institutes of Health supported the work, which appears in Science Advances.
Source: Georgia Tech