Abstract

There are currently no standardized methods for assessing fracture healing, with physicians relying on X-rays which are only useful at later stages of repair. Using in vivo mouse fracture models, we present the first evidence that microscale instrumented implants provide a route for post-operative fracture monitoring, utilizing electrical impedance spectroscopy (EIS) to track the healing tissue with high sensitivity. In this study, we fixed mouse long bone fractures with external fixators and bone plates. EIS measurements taken across two microelectrodes within the fracture gap were able to track longitudinal differences between individual mice with good versus poor healing. We additionally present an equivalent circuit model that combines the EIS data to classify fracture repair states. Lastly, we show that EIS measurements strongly correlated with standard quantitative µCT values and that these correlations validate clinically-relevant operating frequencies for implementation of this technique. These results demonstrate that EIS can be integrated into current fracture management strategies such as bone plating, providing physicians with quantitative information about the state of fracture repair to guide clinical decision-making for patients.

Highlights

  • Musculoskeletal injuries are among the most disabling conditions in the United States, with the total number of bone fractures ranging from 12 to 15 million per year[1]

  • We demonstrated the ability of our sensors to distinguish between healing and poor-healing fractures stabilized using miniaturized external fixators or bone plates, and found that frequency spectra of impedance measurements are robustly correlated with quantified measures of bone volume and bone mineral density

  • We find that normalized resistance (R) significantly correlates with the ratio of bone volume to total volume (BV/TV), bone mineral density (BMD), trabecular number, and trabecular thickness (Fig. 6A–D)

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Summary

Introduction

Musculoskeletal injuries are among the most disabling conditions in the United States, with the total number of bone fractures ranging from 12 to 15 million per year[1]. Plain X-ray radiographs are often used, but studies have shown that these correlate poorly with bone strength, do not define union with enough accuracy, and are unreliable for determining the stage of fracture repair[7]. Hypertrophic maturation of chondrocytes promotes mineralization and leads to conversion of cartilage into trabecular bone (Stage 3)[16], where it is remodeled into functional cortical bone (Stage 4) These four defined stages of healing are well characterized histologically[10,16,17], but early stages in particular are not detectable by typical methods of monitoring like X-ray that rely on mineralization of bone.

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