Although bones have remarkable self-regenerative powers, some conditions frustrate even their most heroic efforts. Outstanding examples include massive shattering (as in automobile accidents), poor circulation in old bones, and certain birth defects. Electrical stimulation. In large or slowly healing fractures, electrical stimulation of the fracture site dramatically increases the speed of healing. A lesson from geology notes that minute electrical currents are produced when minerals are stressed, a phenomenon called the piezo-electric effect. Bone tissue is deposited in regions of negative electrical charge (stressed areas) and absorbed in areas of positive charge, but the process by which applied electricity promotes healing is poorly understood. One theory is that the electrical fields prevent PTH from stimulating the bone-absorbing osteoclasts at the fracture site, thus allowing increased accumulation of bony tissue. Another theory holds that the electrical fields induce production of growth factors that stimulate the osteoblasts. Ultrasound treatments. Daily exposure to pulsed low-intensity ultrasound waves reduces the healing time of broken arms and shinbones by 35–45%. This treatment seems to stimulate cartilage cells to make callus. Free vascular fibular graft. This technique uses pieces of the fibula (the sticklike bone of the leg) to replace missing or severely damaged bone. In the past, extensive bone grafts (typically using pieces of bone from the hip) usually failed because blood could not reach their interior, necessitating eventual amputation. This new technique grafts normal blood vessels along with the bone section. Subsequent remodeling leads to a good replica of the bone normally present. Although bone implants have proved effective in adults, they have been less desirable for children with growing bones because of the limb-length discrepancy that results. This problem has been partially resolved, at least for knee replacement candidates, with self-extending endoprostheses. The telescopic sleeve of these devices (see the figure) undergoes continual automatic limb elongation enforced by knee bending. Overlengthening of the prosthesis is prevented by tension in the surrounding soft tissue, which increases after each elongation and then gradually decreases as the soft tissue grows. Vascular endothelial growth factor (VEGF). VEGF is a protein that stimulates the growth of blood vessels. Researchers have been exploring its potential to create new arteries in people with heart disease, and more recently they began studying VEGF as a way to build new bone tissue. Experiments on mice with bone fractures show that VEGF stimulates the formation of osteoblasts and proteins associated with bone growth. Nanobiotechnology. Researchers are experimenting with nanostructures (Greek nanos = dwarf) that mimic the structure of bone at a microscopic level. Scientists at Northwestern University assembled molecules of synthetic materials into a network of tiny fibers—each 10,000 times narrower than a human hair—similar to the collagen framework of bone tissue. When exposed to calcium and phosphate ions, the fibers developed crystalline deposits similar to those that form bone. Although still in the experimental stage, these fibers could someday be incorporated into a gel and packed into fracture sites to speed healing. Bone substitutes. Desperate for bone fillers, surgeons have traditionally resorted to using crushed bone from cadavers or synthetic materials. Crushed bone induces the body to form new bone of its own. When mixed with water, it can be molded to the shape of the desired bone or packed into small, difficult-to-reach spaces. Thus, it avoids the often painful and timeconsuming procedure of bone grafting. The same can be said for most synthetic bone substitutes, but both approaches have shortcomings. Cadaveric bone carries a small (but real) risk of hepatitis or HIV infection. Additionally, as foreign tissue, it may be rejected by the immune system. Synthetics tend to cause inflammation which hinders healing and promotes infection. Pro Osteon (made from coral) avoids both problems. The coral is heat-treated to kill the living coral cells and convert its mineral structure to hydroxyapatite, the salt in bone. The brittle coral graft is then carved to the desired shape, sterilized by irradiation with gamma rays, and coated with bone morphogenic protein (BMP), a natural substance that enhances bone growth. Osteoblasts and blood vessels migrate from the adjacent natural bone into the coral implant, gradually replacing it with living bone. Research has also produced several types of artificial bone. One is TCP, a biodegradable ceramic substance soft enough to be shaped, but not very strong. TCP’s biggest application has been to replace parts of non-weight-bearing bones, such as skull bones. Norian SRS, a bone cement made of calcium phosphate, provides immediate structural support to fractured or osteoporotic sites. Mixed at the time of surgery, Norian SRS starts out as a paste that can be injected into damaged areas to create an “internal cast.” The paste hardens in minutes and cures into a substance with greater compressive strength than spongy bone. Because its crystalline structure and chemistry are the same as that of natural bone, it is gradually remodeled and replaced by host bone cells. A limitation is that Norian SRS can be used only on the ends of long bones because it cannot resist the twisting and flexing experienced by the central shaft.