Mending mouths: Rebuilding jawbones with stem cells
BACKGROUND: Maxillofacial bone grafting and bone harvesting developed to the scientific level during WWI. The development of radical surgery to treat oral cancers began close to 1906. That effort along with the increase in war-related maxillofacial defects began in 1914. The U.S. Army Medical Corps and the U.S. Army Dental Corps began with a block graft harvest from the lacteral tibia with a reported success rate of 64.5%. During 1918 and 1941, anesthesia became more reliable. The practice of bone harvesting, mostly from the ribs and iliac crest, was utilized in WWII related jaw reconstructions. During WWII one-piece iliac block grafts were used 81% of the time, ribs 15%, one—piece tibia grafts 2%, and chip grafts 1%. In 1944, iliac cancellous bone chips were introduced. After WWII, tumor and civilian trauma were the main indications for mandibular reconstruction and cancellous marrow grafts were the most common. This type of grafting has been popularized in the 1990s and early 2000. Now, free microvascular transfers of the fibula are often used today by nondental surgeons to reconstruct defects of the mandible. Recombinant human bone morphogenetic protein (rhBMP) has shown significant bone regeneration capabilities in maxillofacial and oral bone defects. (Source: Marx, Robert E., Atlas of Oral and Extraoral Bone Harvesting)
HARVESTED BONE: When a bone graft is harvested, there is a period of time before it is placed into the recipient site. It is recommended to minimize the out of body time, but sometimes it can extend up to two hours. The principle of autogenous bone harvesting is to transplant viable osteocompetent cells along with a matrix that contains a signal for bone regeneration. It is necessary to maintain the viability of the grafts. Studies have shown that room-temperature saline preserves more than 95% of graft cell viability for at least four hours. Because autogenous osteocompetent cells and bone marrow stem cells are hardy, they will survive to regenerate bone in most cases unless they are destroyed during the time between harvest and placement. The most common cause of cell viability is contact with sterile distilled water. (Source: Marx, Robert E., Atlas of Oral and Extraoral Bone Harvesting)
NEW TECHNOLOGY: Recombinant human bone morphogenetic protein-2/acellular collagen sponge was FDA approved for orthopedic lumbar spinal fusions, open tibial fractures, oral and maxillofacial sinus floor augmentations and alveolar ridge preservations. It is an alternative to autogenous bone grafting without the morbidity of bone harvesting. It regenerates new bone on its own. The bound BMP in the acellular collagen sponge is chemotactic to stem cells and preosteoblasts. These cells will migrate into the sponge and undergo proliferation and differentiation into osteoblasts, which will then synthesize osteoid. Once this process is complete, the osteoid will undergo the standard remodeling cycle of bone to a mature ossicle in six months. The production of rhBMP-2 begins with restricted enzymes, which is the BMP-2 gene from chromosome 20 in the human genome. This gene is transferred into a bacterial plasmid. Then it is transfected into a chromosome in Chinese hamster ovary cells (CHO) and cultured to increase the numbers. The CHO cells will produce hamster proteins, but also one unique human protein called BMP-2. It is separated to produce a purely human protein free of bacteria or animal proteins and in high concentrations to regenerate bone in humans. (Source: Marx, Robert E., Atlas of Oral and Extraoral Bone Harvesting)
Robert E. Marx, DDS, Professor of Surgery and Chief, Oral and Maxillofacial Surgery at the University of Miami Miller School of Medicine, talks about stem cells for the jawbone.
Now you’re able to create bone instead of using the patient’s own bone to create a jaw bone, is that what’s happening?
Dr. Marx: Yes. It’s called In-situ tissue engineering. We’re able to regenerate large portions of missing bone; at least the jaw bone and not taking any bone from the patients themselves using three things: stem cells aspirated from their bone marrow, recombinant human bone morphogenetic protein (BMP), and cadaver crushed bone, which is sterile from the University of Miami Tissue Bank.
So, you put all of this in with a metal plate in the jaw and it turns into hardened bone in six months?
Dr. Marx: In six months the bone is absolutely normal. Any of the cadaver bone has been dissolved and replaced by the patient’s own bone, stimulated by the BMP, and actually produced by the bone marrow. The metal plate that’s internal stays there as a form of rigid fixation and holds the bone still during the healing process.
How much time does this shave off of a patient’s stay in the hospital from the old method to the new method?
Dr. Marx: It shaves off at least three days, maybe four. In the standard use of open hip grafting, patients are in the hospital for about four days. Another alternative is to take a leg bone called the fibula. Those patients are in the hospital ten days and usually three days in the intensive care unit. With In-situ tissue engineering, the patients are out the next day.
Tell me about Ramsey, what happened to his jawbone?
Dr. Marx: Ramsey suffered complications from a wisdom tooth removal. He developed a pretty serious infection. It progressed to weaken his jaw; then his jaw finally broke and resulted in a significant amount of dead bone that we had to remove.
And how did he respond to the therapy?
Dr. Marx: He responded perfectly. He was a good patient and his otherwise general body health helped him through difficult times. Because we had to remove about four or five inches of his jawbone and replace it, we did it in two separate surgeries. The first one was to eradicate the infection. The second one was to rebuild the bone with this In-situ tissue engineering. Then he had a routine dental implant placement placed. He had not only his bone placed back, but also his teeth placed back through dental implants.
What is this used for, tumors and broken jaws?
Dr. Marx: It can be used in trauma. We’ve done this for gunshot wounds, benign tumors, and for individuals who have had malignant tumors removed as long as they did not have active cancer. This combination works in almost all patients. Right now we’re trying to make it work in the most difficult group and that is the radiated patients, but we are still in research format.
When you take the bone marrow, is it taken at the same time that you replace it into the jaw?
Dr. Marx: Yes. That’s the large advantage of it. It’s the patient’s own bone marrow and it’s essentially at the same time. There is no delay. There’s also no risk of infection by transferring it into a culture plate to an outside institution. It’s very practical and has proven now to be very successful.
Did anybody fund this study?
Dr. Marx: No one funded this study. We do have a research chair that funded this study, but this is not beholden to any company at all. It is internally funded through the University of Miami.
Are you directly or indirectly compensated by the manufacturer for your involvement in this procedure?
Dr. Marx: No, not this particular procedure. I have been a paid consultant to these companies for the FDA required research, but this is not that part. These are our own independent non-funded studies.
Will your hospital or organization benefit financially by this procedure?
Dr. Marx: I think they will only because they have less cost. It’s a shorter operation, less hospital time for a very good reason, and less complications. So, there is less redo. In the long run it saves a lot of their expenses.
What concerns do other doctors have as to why they are not using this procedure?
Dr. Marx: This is a relatively new technique that came from all of our research. We have been developing books. Because it is new, not everyone has been trained in this. So, we are training fellows and residents each year.
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Robert E. Marx, DDS
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