By Vincent T. Davis
Imagine: a soldier loses an arm in an IED blast in Iraq or Afghanistan. A civilian loses a leg in an automobile accident or facial bone from a gunshot. Today their options are few. They could have a surgical amputation and doctors could fit them with a prosthetic limb. Other choices might include replacing the injured bone with bone from a cadaver or another area of the body.
In the future they may have another option. Doctors could regenerate the bone tissue that was lost and patients return to function as they did before their injuries. The College of Engineering at UTSA is working to make bone regeneration for traumatic injuries a reality.
Biomedical engineering researchers received $2 million from the U.S. Army’s Medical Research and Materiel Command and the Institute for Medical Research in November 2007 to study tissue engineering methods. C. Mauli Agrawal, dean of the engineering college and Joo Ong, chair of the bioengineering department, will head the project. They are collaborating with the Army, San Antonio’s Southwest Research Institute, Carnegie Mellon University and the University of Texas Health Science Center at San Antonio. The endowment will be funded for four years.
It’s the largest grant that the College of Engineering has received to date. The award was one of several that the Army distributed nationwide for research in regenerative medicine for the war wounded.
“It’s very evident when you go to the Center for the Intrepid and Brooke Army Medical Center and you look at the patients there and it becomes reality, it’s no longer a science experiment,” Agrawal says. “The need is there, and science has evolved to a point where I think it can all be put together.”
Tissue Engineering
The idea of tissue engineering is to regrow or repair functioning tissues like bone, which usually heals itself. But if there’s a lot of damage in the bone, it does not grow back. With tissue engineering, scientists use cells from a different part of the body and implant them into a scaffold, a three-dimensional shape formed of polymer foam and molded into the shape of missing bone. The scaffold features interconnected holes in a Swiss cheese–like material that allows bone tissue and blood vessels to grow and bridge with existing bone.
Agrawal’s background is working with medical implants and implantable biomaterials. His lab concentrates on cardiovascular and orthopedic biomaterials and has invented methods using scaffolds for creating mineralized occlusions.
Ong’s research of implant biomaterial surfaces for dental and orthopedic applications has resulted in promising bone regeneration results. His laboratory is one of the
few in the nation that focus on generating bone-like scaffolds for dental and orthopedic treatments.
Merging these two specialties and their respective expertise with scaffolds created new possibilities and also new dilemmas. One of the biggest problems was with tissues involving large segments of bone. Bone grafted from the same person has been known to cause secondary trauma, yet bone taken from another human can induce
immune rejection. Together, Agrawal and Ong studied how they could regenerate bone and infiltrate it with blood vessels that are the roadways to bringing nutrition to the cells.
“When you’re talking about a soldier whose femur has been blown apart and there’s seven inches of bone missing, how do you grow that back?” Agrawal asks. “It’s not going to work unless you have arteries going into it.”
The Process
Individually, Agrawal and Ong tested their research in living organisms with promising results. Ong’s scaffold worked successfully in smaller bone defects and had shown it could get nutrition around the scaffold and feed the cells. Agrawal’s polymer scaffold, with a special surface treatment implanted in animals, generated blood vessels.
They had success growing bone cells in a Petri dish, but not actual bone. So the researchers combined their two processes to see if Agrawal’s technology could help generate blood vessels for Ong’s scaffold. The solution came in the form of three components—calcium phosphate (which serves as a growth factor), an antibiotic and a polymer.
The first step involves cutting polymer foam, molding it into the shape of the missing bone and dipping it in a calcium phosphate mixture. Designing a scaffold that is the right size and surface that permits branching into channels and pores is critical. The implant is put in a furnace and baked at 3,000 degrees Fahrenheit for several days. When the foam burns off, it leaves a ceramic portion behind.
Two other components are also integral to the process. Ong said that the calcium phosphate expedites bone regeneration. An antibiotic is also included to reduce the risk of infection in the localized area.
The step that’s critical to regeneration is the insertion of a polymer rod-shaped material in the center of the calcium phosphate that would induce angiogenesis, which creates new blood vessels from pre-existing vessels.
Tissue Research
Bone regeneration has been around since the 1980s. “Until that point in time and even up to today, when there is a defective part in the body, the idea is to go in surgically and excise that part and replace it by a man-made part,” Agrawal says. “The latest philosophy of bone regeneration is slightly different. It says instead of doing that, scientists can help the body heal itself so in the long term, no medical implant will be left in the body.”
Instead of metallic implants, surgeons could use the scaffolds, which contain living tissue and cells to facilitate bone regeneration. The concept started in Boston at Massachusetts Institute of Technology and has spread all over the world, with bioengineers researching methods for regenerating every type of tissue in the human body. Regenerative studies are being done on the kidney, bladder and nerves. Work is also being done in the area of cancer surgery and skin for burn patients.
With the expertise at UTSA, coupled with animal models from the UT Health Science Center and special capabilities at Southwest Research Institute to make scaffolds that fight infections, the outlook is promising, he says. Being in close proximity to wounded soldiers at Brooke Army Medical Center also helps researchers focus on developing a process to decrease devastating injuries.
The Final Phase
The researchers’ work could move into clinical studies in five or six years, Ong says. Once in that final phase, researchers will continue with their work in the lab to
optimize results. The Food and Drug Administration will analyze the procedure and ensure it meets safety standards.
The findings that UTSA researchers yield will add to the history of medical advances that improve the quality of life for soldiers as well as civilians. Agrawal says younger generations might see a day when loss of limb and organs will not be as traumatic as it is today.
“I always tell people and especially
students that in their lifetimes, they’ll drive by and see a sign that says ‘body shop’ and it will have a totally different connotation,” Agrawal says. |
