Combining Electrostimulation with Impedance Sensing to Promote and Track Osteogenesis within a Titanium Implant

Abstract

(1) Background: Electrical stimulation is a promising alternative to promote bone fracture healing but with the limitation of tracking the osteogenesis progress in vivo. To overcome this issue, we present an opportunity to combine the electrical stimulation of a commercial titanium implant, which promotes osteogenesis within the fracture, with a real-time readout of the osteogenic progress by impedance sensing. This makes it possible to adjust the electrical stimulation modalities to the individual patient’s fracture healing process. (2) Methods: In detail, osteogenic differentiation of several cell types was monitored under continuous or pulsatile electrical stimulation at 0.7 V AC/20 Hz for at least seven days on a titanium implant by electric cell-substrate impedance sensing (ECIS). For control, chemical induction of osteogenic differentiation was induced. (3) Results: The most significant challenge was to discriminate impedance changes caused by proliferation events from those initiated by osteogenic differentiation. This discrimination was achieved by remodeling the impedance parameter Alpha (α), which increases over time for pulsatile electrically stimulated stem cells. Boosted α-values were accompanied by an increased formation of actin stress fibers and a reduced expression of the focal adhesion kinase in the cell periphery; morphological alterations known to occur during osteogenesis. (4) Conclusions: This work provided the basis for developing an effective fracture therapy device, which can induce osteogenesis on the one hand, and would allow us to monitor the induction process on the other hand.

Addressing Model Uncertainties in Finite Element Simulation of Electrically Stimulated Implants for Critical-Size Mandibular Defects

“…As a result, it can only deliver a limited amount of current. Therefore, the aforementioned feedback-controlled stimulation process should include measuring and monitoring the tissue impedance directly through the implanted stimulation electrodes, as suggested by Engel et al for electrodes similar to the bipolar ones examined in this study [87]. Such closed-loop stimulation systems utilize a feedback-control system through real-time biosignal processing.…”

Methods to accelerate fracture healing – a narrative review from a clinical perspective

“…Among the current ideas under development are also autonomous implants with combined sensing and acting capabilities that have a feedback loop and that apply interventions depending on live measurements to accelerate healing ( 15 ). Pulsatile electrical stimulation on cells was combined with such a real-time readout by impedance sensing to design a control loop as an example of how an active implant could be regulated in the future ( 27 ). Patient compliance is a problem when the intervention requires active patient cooperation ( 151 ).…”

“…Thus, it is necessary to adapt the stimulation properties to the individual situation. This may be accomplished by combining the sensor and actor capabilities of the implant in a control circuit ( 15 , 27 ). As the resultant movement and interfragmentary strain in the fracture gap certainly depend on the fracture geometry and fracture gap width, CT-based finite element simulations may help to determine the stroke of the micromovement needed for the individual fracture ( 28 , 29 ).…”

Capacitance Contribution of NIH/3T3 Cells Existing on and between Electrodes of an Impedance Biosensor

“…A sensor equipped with a gold electrode was fabricated, employing the ECIS technique to detect impedance variations in seeded cells. This method elucidated the differentiation of stem cells via electrical stimulation [17]. Separately, researchers from the Department of Convergence Engineering at Chung-Ang University developed a gold microelectrode specifically for analyzing human gastric cancer cells (MKN-1) using ECIS.…”