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Posted on Apr 21, 2005, 6 a.m.
By Bill Freeman
In the 1970s, there was a television show called "The Six Million Dollar Man" about a crippled test pilot who was rebuilt with nuclear powered limbs, which gave him superhuman strength and speed. Although such feats of engineering are probably still a long way off, scientists are making great strides in rebuilding organs and tissues using cells, chemicals and synthetic polymers.
In the 1970s, there was a television show called "The Six Million Dollar Man" about a crippled test pilot who was rebuilt with nuclear powered limbs, which gave him superhuman strength and speed. Although such feats of engineering are probably still a long way off, scientists are making great strides in rebuilding organs and tissues using cells, chemicals and synthetic polymers.
One of these scientists is Dr. Cato Laurencin, Lillian T. Pratt Distinguished Professor of Orthopaedic Surgery at the University of Virginia in Charlottesville. In research funded by the National Institutes of Health, National Science Foundation, and National Aeronautics and Space Administration, Laurencin is trying to make new bone using fat tissue and other materials.
A structural jungle gym
To accomplish this, he starts by making a small polymer scaffold, which has about the same strength as much of the bone in the body. Under the microscope, the scaffold looks like a jungle gym made up of a bunch of little glass balls fused together. Each of the balls is composed of a polymer that harmlessly degrades in the body.
To the polymer scaffold, he adds adult stem cells that have been isolated from a patient's fat tissue. "We're interested in using fat-derived stem cells because most people have a ready supply of fat and it's relatively easy to extract some from under the skin," Laurencin said.
The stem cells wiggle through the spaces in between the polymer balls and take up residence inside the scaffold. There they come under the influence of a protein that has been also added to the scaffold. This protein is a member of a family of proteins called bone morphogenetic proteins, or BMPs. These proteins are ordinarily found inside bone, where they promote bone formation and help mend broken bones.
One of the functions of BMPs is to transform adult stem cells in the bone marrow into bone-forming cells, or osteoblasts. Inside the scaffold, a BMP can also turn fat-derived stem cells into osteoblasts, even though they ordinarily would become fat cells if they were back in their old neighborhood of fat tissue.
The scaffold is shaped to fit snugly into an area that needs new bone and then inserted. The osteoblasts go to work making new bone, while the polymer scaffold decomposes into by-products that are metabolized by cells.
Laurencin is currently testing these fat-derived synthetic bone grafts in mice. Results aren't in yet, but a previous study with rabbits showed that his system works well using BMP and bone marrow.
In this study, he cut out a 15-millimeter segment from one of the two long bones in the forearm of each rabbit, which is a gap too large for bones to heal on their own. Ordinarily, the gap would become filled with scar tissue rather than new bone.
Hopping again
To facilitate bone healing, Laurencin inserted a polymer scaffold segment designed to fit precisely into the gap. In one group of rabbits, the scaffolds were treated with BMP. In another, they were filled with rabbit bone marrow. In a third group, the scaffolds contained both bone marrow and BMP, while a fourth received scaffolds containing neither agent.
"Within 48 hours, the rabbits in all groups were getting around and using their forelimbs just like normal," Laurencin said. "I think that shows the promise of our system."
After eight weeks, new bone had grown throughout most of the implants in the BMP and BMP plus bone marrow groups, which is fast healing for such an extensive bone injury. In the BMP group, the protein was able to attract adult stem cells from surrounding tissues into the scaffold, where it turned them into osteoblasts. In the BMP plus bone marrow group, adult stem cells were already in the scaffold because of the bone marrow.
In the groups in which the scaffolds contained only bone marrow or were untreated, bone growth occurred primarily at the intersections between scaffold and existing bone.
Coming soon
Laurencin estimates that the first generation of synthetic bone grafts will be ready for human use in about two to three years. "For 90 percent of cases, I believe that an implant consisting simply of the polymer scaffold will be sufficient to replace the bone grafts being used now," he said. Currently, surgeons take small pieces of bone from the hip of a patient or bone of a cadaver and insert them into areas that need new bone. Taking bone from the hip can cause long-term pain and soreness, while taking bone from a cadaver risks transmitting an infectious agent, such as HIV.
According to Laurencin, the second generation of synthetic grafts will consist of polymer scaffolds treated with BMP, and the third generation will be BMP-treated scaffold plus bone marrow or adult stem cells.
After that, who knows? Nuclear powered osteoblasts, anyone?
One of these scientists is Dr. Cato Laurencin, Lillian T. Pratt Distinguished Professor of Orthopaedic Surgery at the University of Virginia in Charlottesville. In research funded by the National Institutes of Health, National Science Foundation, and National Aeronautics and Space Administration, Laurencin is trying to make new bone using fat tissue and other materials.
A structural jungle gym
To accomplish this, he starts by making a small polymer scaffold, which has about the same strength as much of the bone in the body. Under the microscope, the scaffold looks like a jungle gym made up of a bunch of little glass balls fused together. Each of the balls is composed of a polymer that harmlessly degrades in the body.
To the polymer scaffold, he adds adult stem cells that have been isolated from a patient's fat tissue. "We're interested in using fat-derived stem cells because most people have a ready supply of fat and it's relatively easy to extract some from under the skin," Laurencin said.
The stem cells wiggle through the spaces in between the polymer balls and take up residence inside the scaffold. There they come under the influence of a protein that has been also added to the scaffold. This protein is a member of a family of proteins called bone morphogenetic proteins, or BMPs. These proteins are ordinarily found inside bone, where they promote bone formation and help mend broken bones.
One of the functions of BMPs is to transform adult stem cells in the bone marrow into bone-forming cells, or osteoblasts. Inside the scaffold, a BMP can also turn fat-derived stem cells into osteoblasts, even though they ordinarily would become fat cells if they were back in their old neighborhood of fat tissue.
The scaffold is shaped to fit snugly into an area that needs new bone and then inserted. The osteoblasts go to work making new bone, while the polymer scaffold decomposes into by-products that are metabolized by cells.
Laurencin is currently testing these fat-derived synthetic bone grafts in mice. Results aren't in yet, but a previous study with rabbits showed that his system works well using BMP and bone marrow.
In this study, he cut out a 15-millimeter segment from one of the two long bones in the forearm of each rabbit, which is a gap too large for bones to heal on their own. Ordinarily, the gap would become filled with scar tissue rather than new bone.
Hopping again
To facilitate bone healing, Laurencin inserted a polymer scaffold segment designed to fit precisely into the gap. In one group of rabbits, the scaffolds were treated with BMP. In another, they were filled with rabbit bone marrow. In a third group, the scaffolds contained both bone marrow and BMP, while a fourth received scaffolds containing neither agent.
"Within 48 hours, the rabbits in all groups were getting around and using their forelimbs just like normal," Laurencin said. "I think that shows the promise of our system."
After eight weeks, new bone had grown throughout most of the implants in the BMP and BMP plus bone marrow groups, which is fast healing for such an extensive bone injury. In the BMP group, the protein was able to attract adult stem cells from surrounding tissues into the scaffold, where it turned them into osteoblasts. In the BMP plus bone marrow group, adult stem cells were already in the scaffold because of the bone marrow.
In the groups in which the scaffolds contained only bone marrow or were untreated, bone growth occurred primarily at the intersections between scaffold and existing bone.
Coming soon
Laurencin estimates that the first generation of synthetic bone grafts will be ready for human use in about two to three years. "For 90 percent of cases, I believe that an implant consisting simply of the polymer scaffold will be sufficient to replace the bone grafts being used now," he said. Currently, surgeons take small pieces of bone from the hip of a patient or bone of a cadaver and insert them into areas that need new bone. Taking bone from the hip can cause long-term pain and soreness, while taking bone from a cadaver risks transmitting an infectious agent, such as HIV.
According to Laurencin, the second generation of synthetic grafts will consist of polymer scaffolds treated with BMP, and the third generation will be BMP-treated scaffold plus bone marrow or adult stem cells.
After that, who knows? Nuclear powered osteoblasts, anyone?
