Measuring and modulating angiogenesis during fracture healing

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Complications in fracture healing often result from insufficient blood supply to the healing bone. In order for bone to form, blood vessels must invade the tissue, bringing proper nutrients and cells to the tissue. The formation of blood vessels, called angiogenesis, is critical to fracture healing. This project examines the growth of blood vessels during fracture healing in a rat femur as well as how the mechanical environment may alter blood vessel growth. In this project micro-computed tomography (microCT) and laser Doppler and will be used to quantify and visualize angiogenesis at important time points during fracture healing. Angiogenesis is necessary, but not sufficient, for bone formation during fracture healing. Under certain mechanical environments, bone growth does not occur even with an adequate blood supply. External fixation on a rat femur fracture allows one to alter the mechanical environment during the healing process. The influence of three different loading conditions on fracture healing will be investigated: (1) static fixation, (2) interfragmentary compression, and (3) static tension. Vascular flow, volume, and structure will be assessed for the three loading conditions and compared. After removing the bone from the body, the stiffness properties of the callus, which measure how well it has healed, will be determined. Understanding the role of angiogenesis in fracture healing is valuable in determining why some fractures do not heal under certain conditions.