Wireless Implantable Sensor for Noninvasive, Longitudinal Quantification of Axial Strain Across Rodent Long Bone Defects

Abstract

Bone development, maintenance, and regeneration are remarkably sensitive to mechanical cues. Consequently, mechanical stimulation has long been sought as a putative target to promote endogenous healing after fracture. Given the transient nature of bone repair, tissue-level mechanical cues evolve rapidly over time after injury and are challenging to measure noninvasively. The objective of this work was to develop and characterize an implantable strain sensor for noninvasive monitoring of axial strain across a rodent femoral defect during functional activity. Herein, we present the design, characterization, and in vivo demonstration of the device's capabilities for quantitatively interrogating physiological dynamic strains during bone regeneration. Ex vivo experimental characterization of the device showed that it possessed promising sensitivity, signal resolution, and electromechanical stability for in vivo applications. The digital telemetry minimized power consumption, enabling extended intermittent data collection. Devices were implanted in a rat 6 mm femoral segmental defect model, and after three days, data were acquired wirelessly during ambulation and synchronized to corresponding radiographic videos, validating the ability of the sensor to noninvasively measure strain in real-time. Together, these data indicate the sensor is a promising technology to quantify tissue mechanics in a specimen specific manner, facilitating more detailed investigations into the role of the mechanical environment in dynamic bone healing and remodeling processes.

Recapitulating bone development for tissue regeneration through engineered mesenchymal condensations and mechanical cues

“…This suggests that ambulatory imbalance is low or not sufficient to alter loadinduced bone regeneration. Daily observation of animal ambulation and in vivo x-ray videography 15,30 during treadmill ambulation demonstrate that compliant plates do not impair weight bearing in either limb during ambulation. Further, we previously evaluated gait kinematics in response to fixation plate insertion and bone 23 defect creation and found no significant differences between groups or compared to sham-operated controls, indicating that defect creation and fixation implantation does not significantly alter gait kinematics.…”

“…Further, we previously evaluated gait kinematics in response to fixation plate insertion and bone 23 defect creation and found no significant differences between groups or compared to sham-operated controls, indicating that defect creation and fixation implantation does not significantly alter gait kinematics. 30 One limitation of this study was our use of only one hMSC donor. A single donor was chosen to reduce the compounding factor of donor variability.…”

“…A recent in vivo strain sensor study using a modified version of the stiff plates described here confirmed these numbers within one percent for the stiff group. 30 The amount of strain induced over time is a function of the load sharing, and therefore dependent on the amount, composition, and kinetics of tissue ingrowth; however, accounting for load sharing by ingrowing bone, we estimated strains of 5-10% upon plate unlocking at week 4 in the delayed group, with all groups converging on 0.5-3% by week 12.…”

Real-time monitoring of mechanical cues in the regenerative niche reveal dynamic strain magnitudes that enhance bone repair

“…A new digital transceiver unit was developed to provide a number of key functional improvements over the unit reportedly previously ( 22 ), mainly: (i) increased power budget and (ii) sampling frequency, (iii) improved connectivity via Bluetooth Low-Energy (BLE) wireless network, and (iv) remote-controlled circuit calibration. The unit used a BLE microcontroller (MCU) (Silicon Labs BLE113) to receive commands and transmit data at an increased frequency of 30 Hz through a PC-mounted USB receiver.…”

“…Using a pre-clinical rat model of long bone repair, we observed that varying load transfer modulates vascular and skeletal tissue formation after injury ( 7 , 17 ). Motivated to better understand the temporal progression of tissue-level mechanical cues that could enhance skeletal repair, we recently developed a fully implantable strain sensor platform enabling real-time monitoring of mechanical boundary conditions across the defect during functional rehabilitative activities like walking ( 22 ). The device possesses sufficient sensitivity and size for implementation in rats--animals which are used commonly used as a key pre-clinical test bed to screen therapeutic approaches before scaling up to more costly large animal models.…”