Implantable microelectromechanical sensors for diagnostic monitoring and post‐surgical prediction of bone fracture healing

The relationship between modern clinical diagnostic data, such as from radiographs or computed tomography, and the temporal biomechanical integrity of bone fracture healing has not been well‐established. A diagnostic tool that could quantitatively describe the biomechanical stability of the fracture site in order to predict the course of healing would represent a paradigm shift in the way fracture healing is evaluated. This paper describes the development and evaluation of a wireless, biocompatible, implantable, microelectromechanical system (bioMEMS) sensor, and its implementation in a large animal (ovine) model, that utilized both normal and delayed healing variants. The in vivo data indicated that the bioMEMS sensor was capable of detecting statistically significant differences (p‐value <0.04) between the two fracture healing groups as early as 21 days post‐fracture. In addition, post‐sacrifice micro‐computed tomography, and histology data demonstrated that the two model variants represented significantly different fracture healing outcomes, providing explicit supporting evidence that the sensor has the ability to predict differential healing cascades. These data verify that the bioMEMS sensor can be used as a diagnostic tool for detecting the in vivo course of fracture healing in the acute post‐treatment period. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1439–1446, 2015.

[1]  Diane Hu,et al.  A model for intramembranous ossification during fracture healing , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[2]  C. Puttlitz,et al.  Metamaterial-based wireless strain sensors , 2009 .

[3]  S M Perren,et al.  Functional load of plates in fracture fixation in vivo and its correlate in bone healing. , 2000, Injury.

[4]  Brandon Santoni,et al.  Nested Metamaterials for Wireless Strain Sensing , 2010, IEEE Journal of Selected Topics in Quantum Electronics.

[5]  S. Trippel Potential role of insulinlike growth factors in fracture healing. , 1998, Clinical orthopaedics and related research.

[6]  J. Johnston,et al.  Direct in vivo strain measurements in human bone-a systematic literature review. , 2012, Journal of biomechanics.

[7]  P Augat,et al.  Biomechanical methods for the assessment of fracture repair. , 2014, Injury.

[8]  Michael J Fagan,et al.  A Single-Channel Telemetric Intramedullary Nail for In Vivo Measurement of Fracture Healing , 2009, Journal of orthopaedic trauma.

[9]  Hiroshi Fukuda,et al.  Recombinant Human Basic Fibroblast Growth Factor Accelerates Fracture Healing by Enhancing Callus Remodeling in Experimental Dog Tibial Fracture , 1998, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[10]  P. Ogrodnik,et al.  Measuring multi-dimensional, time-dependent mechanical properties of a human tibial fracture using an automated system , 2007, Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine.

[11]  C. Puttlitz,et al.  RF-MEMS Load Sensors with Enhanced Q-factor and Sensitivity in a Suspended Architecture. , 2011, Microelectronic engineering.

[12]  M. Gomez-Benito,et al.  Monitoring In Vivo Load Transmission Through an External Fixator , 2010, Annals of Biomedical Engineering.

[13]  C. R. Howlett,et al.  Effect of platelet-derived growth factor on tibial osteotomies in rabbits. , 1994, Bone.

[14]  Hamish Simpson,et al.  Delayed union and nonunions: epidemiology, clinical issues, and financial aspects. , 2014, Injury.

[15]  Hilmi Volkan Demir,et al.  Metamaterial based telemetric strain sensing in different materials , 2010, Optics express.

[16]  C. Lu,et al.  Effects of delayed stabilization on fracture healing , 2007, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[17]  E Schneider,et al.  Loads acting in an intramedullary nail during fracture healing in the human femur. , 2001, Journal of biomechanics.

[18]  R. Schmidhammer,et al.  Alleviated tension at the repair site enhances functional regeneration: the effect of full range of motion mobilization on the regeneration of peripheral nerves--histologic, electrophysiologic, and functional results in a rat model. , 2004, The Journal of trauma.

[19]  M. Bolander,et al.  Transforming growth factor-beta in the regulation of fracture repair. , 1990, The Orthopedic clinics of North America.

[20]  J. Hua,et al.  Correlation of radiographic and telemetric data from massive implant fixations. , 2006, Journal of biomechanics.

[21]  Hilmi Volkan Demir,et al.  Metamaterial-based wireless RF-MEMS strain sensors , 2010, 2010 IEEE Sensors.

[22]  N Weinrich,et al.  Telemetric assessment of bone healing with an instrumented internal fixator: a preliminary study. , 2012, The Journal of bone and joint surgery. British volume.

[23]  J. L. Cunningham,et al.  Monitoring the Mechanical Properties of Healing Bone , 2009, Clinical orthopaedics and related research.

[24]  M. Menger,et al.  Development of a reliable non-union model in mice. , 2008, The Journal of surgical research.

[25]  K. Dickson,et al.  Delayed unions and nonunions of open tibial fractures. Correlation with arteriography results. , 1994, Clinical orthopaedics and related research.

[26]  J Kenwright,et al.  Manual assessment of fracture stiffness. , 1996, Injury.

[27]  R Bourgois,et al.  Measurement of the stiffness of fracture callus in vivo. A theoretical study. , 1972, Journal of biomechanics.

[28]  Theodore Miclau,et al.  Outcome assessment in clinical trials of fracture-healing. , 2008, The Journal of bone and joint surgery. American volume.

[29]  Christian M. Puttlitz,et al.  Bio-implantable passive on-chip RF-MEMS strain sensing resonators for orthopaedic applications , 2008 .

[30]  V. Rosen,et al.  Novel regulators of bone formation: molecular clones and activities. , 1988, Science.

[31]  A. Wentzensen,et al.  Stiffness measurement of the neocallus with the Fraktometer FM 100® , 2005, Archives of Orthopaedic and Trauma Surgery.

[32]  Christian M. Puttlitz,et al.  Flexible metamaterials for wireless strain sensing , 2009 .

[33]  Christian M. Puttlitz,et al.  Circular High-Q Resonating Isotropic Strain Sensors with Large Shift of Resonance Frequency under Stress , 2009, Sensors.

[34]  R. Wade,et al.  Reliability of radiographs in defining union of internally fixed fractures. , 2004, Injury.

[35]  V. Rosen,et al.  Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[36]  I. Katardjiev,et al.  Etch rates of crystallographic planes in Z-cut quartz - experiments and simulation , 1998 .

[37]  J. O'Connor,et al.  Validation of a lower limb model with in vivo femoral forces telemetered from two subjects. , 1997, Journal of biomechanics.