Abstract
Introduction and Objective
It is widely accepted that interfragmentary strain stimulus promotes callus formation during secondary bone healing. However, the impact of the temporal variation of mechanical stimulation on fracture healing is still not well understood. Moreover, the minimum strain value that initiates callus formation is unknown. The goal of this study was to develop an active fixation system that allows for in vivo testing of varying temporal distribution of mechanical stimulation and that enables detection of the strain limit that initiates callus formation.
Materials and Methods
We employed a previously established wedge defect model at the sheep tibia. The model incorporates two partial osteotomies directed perpendicularly to each other, thus creating a bone fragment in the shape of a wedge. The defect was instrumented with an active fixator that tilts the wedge around its apex to create a gradient of interfragmentary strain along the cutting line. The active fixator was equipped with a force and displacement sensors to measure the stiffness of the repair tissue during the course of healing. We developed a controller that enabled programming of different stimulation protocols and their autonomous execution during the in vivo experiment. The system was implanted in two sheep for a period of five weeks. The device was configured to execute immediate stimulation for one animal (stimulation from Day 1), and delayed stimulation for the other (stimulation from Day 22). The daily stimulation protocol consisted of 1’000 loading events evenly distributed over 12 hours from 9:00 am to 9:00 pm. The healing progression was monitored by the in vivo stiffness measurements provided by the fixator and by weekly radiographs. The impact of the local strain magnitude on bone formation was qualitatively evaluated on a post-mortem high-resolution CT scan of the animal with immediate stimulation.
Results
The animals tolerated the fixator system well. Both devices operated seamlessly throughout the entire experiment. Callus formation was initiated earlier for the immediately stimulated animal which was also confirmed by a faster stiffness increase. In this pilot feasibility experiment, the initiation of callus formation was observed between 0% and 4% local interfragmentary strain.
Conclusions
We developed an autonomous stimulation system for large animal research that enables systematic investigation of fracture healing processes. The in vivo pilot study demonstrated the feasibility of the system and delivered first interesting insides on temporal stimulation impact and callus induction strain limit. These observations, however, require further validation.
