This protein is a replication of bone morphogenetic protein-2 (BMP-2), which occurs naturally in humans and is important in healing and regenerating bone. The key element to Infuse bone graft is rhBMP-2 which is manufactured using well-established molecular biology techniques. The rate of bone formation, the amount of bone formed, and the density of the resulting bone are positively correlated with both the concentration of rhBMP-2 and the length of time that rhBMP-2 is present at the implant site. The ability of rhBMP-2 to induce new bone formation depends on its concentration. Pre-clinical studies support that the bone formation started by rhBMP-2/ACS is self-limiting, forming a predictable amount of bone at the site of implantation. The bone formation process develops from the outside of the rhBMP-2/ACS implant towards the center until the entire implant is replaced by trabecular bone. Blood vessel formation (angiogenesis) is observed at the same time. Step 5: Bone formationĪs the sponge degrades or dissolves, these stem cells differentiate into osteoblast and begin to form trabecular bone and/or cartilage. The researchers concluded that BMP-2, BMP-6, and BMP-9 may be the most potent agents to induce osteoblast lineage-specific differentiation of mesenchymal stem cells. Alkaline phosphatase activity - a measure of the amount of new bone formation - was significantly increased in all three cell lines by BMP-2, BMP-6, and BMP-9. 20 Three cell lines, representing the different stages of osteoblast differentiation, were each tested. 3-19Ī 2003 in-vitro study compared the bone-forming activity of 14 recombinant human bone morphogenetic proteins. 1 Pre-clinical studies have shown that rhBMP-2 can cause the differentiation of precursor cells into osteoblasts. 2, 7 In-vitro studies of rhBMP-2 support the fact that differentiation of mesenchymal stem cells into bone-forming osteoblasts plays an essential role in the induction of new bone. 3-7 Step 4: Differentiationīinding to specific receptors on the surface of the MSC, rhBMP-2 causes them to differentiate into bone-forming cells. In-vitro studies have shown that rhBMP-2 can increase the proliferation of several multipotent cell lines, which can differentiate into osteoblasts, or bone-forming cells. The mesenchymal stem cells around the rhBMP-2/ACS implant increase in number. Mesenchymal stem cells (MSC) move from bleeding bone, muscle, and the periosteum to infiltrate the implant. This cell migration stimulated by a chemical response is called chemotaxis. Step 2: Chemotaxisīone-forming cells migrate to the area of the rhBMP-2/ACS implant. Only when they're used together do they initiate the bone induction process. Neither the rhBMP-2 nor the ACS can produce new bone tissue independently. Based on these observations, bioactive glasses are a promising group of unique biomaterials to act as bone graft substitutes.When rhBMP-2 is placed on an ACS and implanted in the body, it produces new bone tissue at the site of implantation. However, a recent study showed that an adjunct antiresorptive therapy (zoledronic acid) is even beneficial for bone incorporation of bioactive glass. Since osteopromotive silica-based bioactive glasses induce accelerated local bone turnover, adjunct antiresorptive agents may affect the process. Many osteoporotic fracture patients are candidates for concurrent treatment with bisphosphonates and bioceramic bone graft substitutes. Recent studies of molecular biology have shown that bioactive glass induces a high local turnover of bone formation and resorption. In vivo, there is a dynamic balance between intramedullary bone formation and bioactive glass resorption. In a recent study, the activity of the material was found even to overshadow the effect of BMP-2 gene therapy. In vivo, the material is highly osteoconductive and it seems to promote the growth of new bone on its surface. The critical feature for the rate of bioactivity is a SiO2 content < 60% in weight. Bioactive glasses have different rates of bioactivity and resorption rates depending on their chemical compositions. They have several unique properties compared with other synthetic bioresorbable bioactive ceramics, such as calcium phosphates, hydroxyapatite (HA) and tricalcium phosphate (TCP). Bioactive glasses are a group of synthetic silica-based bioactive materials with bone bonding properties first discovered by Larry Hench. Bone grafting procedures are undergoing a major shift from autologous and allogeneic bone grafts to synthetic bone graft substitutes.
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