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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.
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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.
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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.” |
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