Effect, mechanism, and application of a novel micromotional technology on fracture healing

Abstract

Despite recent advances in modern medicine, the incidence of delayed fracture union and nonunion remains high. Some degree of micromotion is proven to accelerate fracture healing; therefore, micromotional/dynamic fixators have been designed to reduce nonunion rate. However, fracture healing is only promoted at certain micromotion parameters, and previous fixator studies have failed to apply precise and controllable micromotion to the fracture site. The lack of reliable and reproducible small animal models has also hindered the study of the micromotion parameters that determine fracture healing. Consequently, the mechanism by which micromotion affects healing is also not clear. The aims of this project were (1) to develop an experimental device that would produce standardized micromotion for rat fracture models; (2) to investigate the effect of micromotion on fracture healing and to determine the optimal strain range; (3) to investigate the mechanism by which micromotion affects fracture healing; and (4) to design an orthopedic external fixator with productization potential that could apply micromotion.

As a first step, a modularized micromotional device with a non-contact measurement module was developed based on video identification technology. A rat femur fracture model was used. The effectiveness and accuracy of this device were evaluated by mechanical tests. Preliminary validation was performed in rats to provide a solid base for a reliable and reproducible method that could be used in subsequent investigations on the effect of micromotion on bone healing.

The effect of different micromotional ranges (0, 10, 20, 30, and 40% interfragmentary strain) on fracture healing was then evaluated by radiography, microcomputed tomography, histological observations, and biomechanical tests. A 10-20% strain was optimal, as indicated by a large callus volume and good mechanical properties. A micromotion exceeding 30% did not increase the callus volume and led to delayed union or nonunion.

Evaluation of fractures stimulated by different strains (0, 10, and 40%) by histological and immunohistochemical tests revealed the mechanism by which micromotion affected fracture healing. Comparison with the 0% group revealed that 10% micromotion inhibited osteoclast activity and enhanced cartilage formation and ossification by downregulating RANKL expression. By contrast, excessive micromotion (40%) activated osteoclasts and caused delayed union and nonunion by upregulating the expression of RANKL and OPG.

A motor-driven fixator, in the form of a micromotional unit (MMU), was developed based on controllable micromotional technology. The MMU can measure movement in real time and make real-time compensations to ensure consistency with pre-set micromotional parameters. A simulation test showed that the MMU possesses significant advantages over the Orthofix® manual micromotional fixator in terms of the accuracy of its micromotional range and frequency.

In conclusion, the modularized experimental fixator is a reliable and reproducible device for evaluating effects of micromotion on bone healing. An interfragmentary strain of 10-20% is the optimal micromotion range for fracture healing. Appropriate micromotion enhances cartilage formation and ossification by inhibiting osteoclast activation, whereas insufficient or excessive micromotion impedes healing by activating osteoclasts. The accuracy of micromotional range and frequency was much higher for the MMU than for a commercial micromotional fixator.