Improved Healing of Large, Osseous, Segmental Defects by Reverse Dynamization: Evaluation in a Sheep Model

Principal Investigator: EVANS, CHRISTOPHER H
Institution Receiving Award: MAYO CLINIC
Program: PRORP
Proposal Number: OR120192
Award Number: W81XWH-13-1-0324
Funding Mechanism: Translational Research Partnership Award
Partnering Awards: OR120192P1
Award Amount: $855,958.00


Objectives and Rationale: Although broken bones normally have the ability to heal naturally, this capability is lost when large sections of bone are lost to create a so-called segmental defect. The objective of the proposed research is to improve the healing of such segmental defects. This will be achieved by manipulating the mechanical environment around the defect. Bone is very responsive to mechanical forces, and we have shown in studies using rats that the healing of segmental defects can be greatly improved by changing these forces. This is achieved with the use of a device known as an external fixator that is applied to the bone surrounding the defect. The stiffness of fixator can be adjusted. Data from the rat studies showed that healing is accelerated and the quality of the bone improved, if the stiffness of the fixator is, first, low and then adjusted at a certain point to provide high stiffness.

Before the results of such studies can be extended to heal human bones with large segmental defects, it is necessary to demonstrate that the technology is effective in large animals whose weight and bone structure are closer to that of humans. For this purpose, we propose to use sheep. We have designed new fixators with adjustable stiffness for sheep. If this proposal is funded, we will construct these fixators and confirm that they have the correct mechanical properties. They will then be used to stabilize large segmental defects created in the shin bones of sheep. Using an approach that was previously successful in rats, the fixator will first provide low stiffness and, when healing has started, it will be adjusted to provide high stiffness. Other animals will not have the stiffness of their fixators adjusted and yet others will have the stiffness adjusted in the reverse fashion, i.e., high stiffness at the beginning and low stiffness later.

After 6 months the animals will be euthanized and the quality of the healed bone compared by a variety of analytical techniques.

Ultimate Applicability: If successful, this research will lead to the development of an inexpensive and simple, yet effective, method for healing large segmental defects in human long bones. As stated below, this is of particular benefit to military populations because extensive loss of bone often occurs as a result of warfare. However, civilian populations will also benefit, as large segmental defects are also a result of civilian injuries and surgery to remove tumors in bone.

Although this particular research project focuses on large segmental defects, the technology it will develop could also be used to address other clinical settings where bone healing is a problem. There is also the possibility of using it to accelerate fracture healing in general.

Benefit to Military Populations, Impact on Combat-Relevant Orthopaedic Research, and Patient Care: During combat, military populations are at high risk of segmental bone loss as a result of blast injuries. Such injuries often lead to amputation. If successful, our technology will provide a simple way to improve healing and restore full function. Because the application of the fixators we have designed does not involve major surgery, they should be particularly valuable under conditions of war, where they could be applied in a field hospital, for instance. The new principles developed as a result of this research should have wide applicability to the healing of bone and, perhaps, soft tissues.