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)