Abstract
There is an unmet need for improved, clinically relevant methods to longitudinally quantify bone healing during fracture care. Here we develop a smart bone plate to wirelessly monitor healing utilizing electrical impedance spectroscopy (EIS) to provide real-time data on tissue com-position within the fracture callus. To validate our technology, we created a 1-mm rabbit tibial defect and fixed the bone with a standard veterinary plate modified with a custom-designed housing that included two impedance sensors capable of wireless transmission. Impedance magnitude and phase measurements were transmitted every 48-hours for up to 10-weeks. Bone healing was assessed by X-ray, μCT, and histomorphometry. Our results indicated the sensors successfully incorporated into the fracture callus and did not impede repair. Electrical impedance, resistance, and reactance increased steadily from weeks 3 to 7—corresponding to the transition from hematoma to cartilage to bone within the fracture gap—then plateaued as the bone began to consolidate. These three electrical readings significantly correlated with traditional measurements of bone healing and successfully distinguished between union and not healed fractures, with the strongest relationship found with impedance magnitude. These results suggest that our EIS smart bone plate can provide continuous and highly sensitive quantitative tissue measurements throughout the course of fracture healing to better guide personalized clinical care.
Competing Interest Statement
M.M.M., M.C.L, M.T.M, C.S.B., S.T.H. declare inventorship and royalties related to the patent #WO2017030900A1. C.S.B, N.F, V.R.D, M.Z.H, I.S., J.H. are/were all paid employees of the non-profit Steadman Philippon Research Institute (SPRI) at the time the research was conducted. SPRI exercises special care to identify any financial interests or relationships related to research conducted here. During the past calendar year, SPRI has received grant funding or in-kind donations from Arthrex, DJO, MLB, Ossur, Siemens, Smith & Nephew, XTRE, and philanthropy. These Institutional funding sources provided no support for the work presented in this manuscript. M.M.M. is an employee of Iota Biosciences, Inc., a fully owned subsidiary of Astellas Pharma.