Speed Healing

Breaking a bone might not seem like such a big deal. Put it in a cast and wait six weeks, and presto, you’re good as new.

For hundreds of thousands of patients in the U.S. each year, the bone-healing process isn’t so easy. Pins, screws and plates might be required, or the damage to the bone might be so severe that bone must be transplanted from elsewhere on the body or from a donor. Even with bone harvested from the patient, the procedure poses significant risks of infection, nerve damage, loss of function, and hemorrhage. The healing process is a complicated cascade of easily disrupted events, and sometimes wounds do not heal adequately.

On the battlefield, the situation is even more challenging. Usually healing an infection must be done prior to treating structural damage to the bones.

Vanderbilt Assistant Professor of Chemical Engineering Scott Guelcher and his associates are creating devices that give the body the extra structure and chemical support it needs to fight infection and grow new bone, then quietly degrade and disappear.

Bone implants are nothing new; surgeons have been using such substitutes for decades. But Guelcher and his associates are developing devices that can not only fill in fractures and take over the load-bearing functions of bone, but also serve as a delivery system for medications that can help new bone tissue to grow in the device’s place.

“We are designing and synthesizing biodegradable and biocompatible polymeric biomaterials that can serve as temporary matrices to enhance bone fracture healing through the natural tissue-remodeling process,”
Guelcher says. “Because of its mechanical and biological properties, we are focusing on polyurethane.”

Polyurethane might seem like a strange substance to have in your body, but with the proper chemical tweaking, it turns out to be an excellent material to give the body the support it needs during the bone-repair process before the device itself fades away.

Grow your own

“Polyurethane is porous but strong,” Guelcher says. “It can be engineered to release tissue-regeneration chemicals and it can be successfully seeded with the patient’s own bone cells.”

His research group has grown natural bone on a polyurethane scaffold in an ex-vivo bioreactor. “We have engineered the mechanical properties of the polyurethane scaffold material and have implemented novel perfusion strategies to culture bone marrow stromal cells.” (A stromal cell is a type of stem cell.) Using these techniques, physicians would be able to extract the patient’s own bone marrow cells, seed them onto the polyurethane scaffold, and put the seeded structure in a bioreactor that keeps the cells supplied with fluids and nutrients they need to grow and replace the scaffold.

“These materials could have application as implants to stimulate bone healing in vivo,” Guelcher says. He is partnering with researchers at Virginia Tech in this project.

His research for the Center for Military Biomaterials and the Army Institute for Surgical Research will produce a material that can not only promote bone healing, but can control infection.

Since most war-time wounds are infected, military doctors would like to simultaneously treat the fracture and the infection. “Right now physicians are having to clear out the
infection before they treat the fracture,” Guelcher says. “They want to treat both the fracture and the infection at the same time.” That’s a multi-faceted problem, but Guelcher is making significant progress.

“We are designing a material that will control several problems at different time scales,” Guelcher says. “We want the material to degrade significantly over six to eight weeks and to deliver antibiotics and growth factors the first two weeks.”

Guelcher and his associates are working out the formulations of antibiotics and growth factors to stimulate the complex healing process.

With recent discoveries that have shown that platelet-derived growth factor (PDGF) will promote bone healing, Guelcher’s team is exploring ways to engineer polyurethane to release PDGF. PDGF is currently FDA-approved for clinical use in healing periodontal lesions.

Injectable foam

Equally appealing to physicians is Guelcher’s minimally invasive injectable foam. These polyurethane foams can be injected at the site of the fracture, hardening into the desired structure while delivering the growth factors that encourage proliferation of bone-producing cells. The polyurethane structure degrades over time and is eliminated by the body.

Guelcher is also working with Vanderbilt’s Ginger E. Holt, assistant professor of orthopaedics and rehabilitation, to devise scaffolds to grow bone in bioreactors that is transplanted in rats. They have successfully grown bone using coral as the scaffolding material, and Holt has developed techniques that encourage growth of blood vessels to the new bone grown within the coral matrix. Coral is not readily biodegradable, so Guelcher is developing a polymer for the scaffold that will help bone to grow and then will be reabsorbed back into the body.

“I find it exciting to do basic science into how materials interact with living tissue,” Guelcher says. “I am enjoying working with people in the Vanderbilt Medical Center to take these innovations from bench to bedside.”