Boning Up: Surgeons and researchers team to build better bone

boning-up-taylor

A better way: Dissatisfied with the results of bone reconstruction, surgeon Jesse Taylor found a solution in patients’ own stem cells.


In a first-ever achievement, a research team at Cincinnati Children’s has found a way to grow a better bone, using stem
cells from a surprising source.

In the US alone, some seven million people have what plastic surgeon Jesse Taylor, MD, calls “defects in bony continuity” so severe, it is difficult to adequately repair them with surgery.

These bony deficits can be caused by tumors, trauma or infection. Whatever the cause, the result is that those affected are left with significant gaps in their skeletal structure. And the “cure” for repairing these gaps leaves much to be desired, says Taylor, a physician and researcher in the Division of Plastic Surgery at Cincinnati Children’s.

“Currently, reconstructive surgeons borrow another part of the body to recreate what’s been removed,” he says. “It is a reasonable alternative, but it’s not perfect.”

Building Bone

So Taylor and his team are working on a better way – with some remarkable success. Collaborating with Taylor on this effort are Donna Jones, PhD; Rian Maercks, MD; and Chris Runyan, PhD. Working with an animal model, they use mesenchymal stem cells taken from fat and inject a growth factor called bone morphogenic protein 2 (BMP-2). They pipette the cells and growth factor into biocleansed cadaver bones, then wrap them in periosteal or other highly vascularized tissue to keep the bone alive and growing.

The result is something no one else has been able to do. “We have basically engineered histologically normal, healthy bone from scratch,” he says.

It’s a process that could potentially benefit the millions of people who live with those significant bony defects. At Cincinnati Children’s alone, Taylor says, some 200 children operated on each year for bony and soft tissue tumors could be helped by the technique.

From the OR to the Bench

The idea came from frustration over surgeries that produced less than ideal results, Taylor says.

“When we remove affected bone, we insert in its place a piece of metal or plastic, which the body tries to reject. Or we use cadaver bone that doesn’t easily vascularize, so it eventually begins to be reabsorbed by the body,” he says. “It’s essentially a race between the bone becoming revascularized and the body eating it up and making it go away. This is our current standard of care.”

It’s a standard that for many people has meant eventual loss of function, pain – and often, additional surgeries.

From left to right: Chris Runyan, PhD, Rian Maercks, MD, and Donna Jones, PhD.

Team effort: Drs. Chris Runyan, Rian Maercks and Donna Jones worked with Taylor to develop the bone growing technique.


Jesse Taylor, MD, is a plastic and reconstructive surgeon at Cincinnati Children’s and assistant
professor, University of Cincinnati College of Medicine.

Chris Runyan, PhD, is a researcher in the Division of Developmental Biology.

Rian Maercks, MD, is chief resident, Division
of Plastic Surgery
.

Donna Jones, PhD, is a researcher in the Division of Plastic Surgery.

The Perfect Solution

The new method would fill the void with living bone created from the individual’s own stem cells, avoiding both rejection and reabsorption. Additionally, says Taylor, “The ideal solution should replicate the form and function of the bone and have the capacity to heal. The bone we’ve developed has all of these attributes.”

How It’s Done

Currently, Taylor’s team is growing this nearperfect bone with an animal model, using the mandible of a pig. They start with stem cells taken from a ready source: fat. The stem cells are cultured in the lab, where they essentially begin to multiply and take on the characteristics of bone cells. They are then placed into a scaffold of cadaver bone, which helps shape the new bone as it grows. The BMP-2 growth factor is added, and the bone is wrapped in a sleeve of highly vascularized tissue to provide blood supply for growth.

Using the method described above, they have been able to achieve what Taylor describes as “essentially normal” bone growth within 50 days. He is so confident in the success of the procedure, he hopes to use it in humans within a year.

Keeping Blood Flowing

One major obstacle to successfully “growing” bone has been the ability to properly vascularize it, an obstacle that Taylor and his team have overcome in large part because of their work in plastic surgery.

“The biggest hurdle for tissue engineers is bringing in blood supply, and we’ve overcome that hurdle,” he says. “If we plastic surgeons have any unique skills, it’s that we know a lot of little tricks for bringing in the vessels and other blood supply.”

These “tricks” have included running vessels through the cadaver bone and wrapping it in highly vascularized sleeves of periosteum and muscle; the methods have proven highly successful at keeping the bone alive and growing.

Next Steps

Taylor says once the method can be used in human beings, he expects that in some cases, particularly in older children, surgeons may be able to obtain enough stem cells from the body fat that the procedure could be done in a single session. In cases where more time is needed for the stem cells to multiply, he anticipates that the person himself could serve as an incubator for growing the new bone.

While he can’t yet say whether the newly created bone will grow normally enough to eliminate the need for repeat surgeries, Taylor is certain that it won’t disintegrate through reabsorption, a problem that occurs in nearly 40 percent of all bone replacements.

Taylor and his group hope to publish their findings soon. They have been painstaking in documenting their results because the researchers themselves have been surprised by what they’ve found.

“We’ve really been very critical of what we’ve done and tried to look at everything,” he says. “We’ve done detailed radiographic studies and micro-CT studies of the bone, the bone density, the amount of calcitic tissue, and the amount of vessel growth, because we don’t want to make a claim that we don’t think we can substantiate.” Even under careful scrutiny, the results appear to speak for themselves, and offer a great deal of hope where frustration used to be the rule.

“To turn this scenario from a sixty percent success rate to a hundred percent success rate would make a big difference for a lot of these kids,” Taylor says.