Programable Active Fixator System for Systematic In Vivo Investigation of Bone Healing Processes

This manuscript introduces a programable active bone fixator system that enables systematic investigation of bone healing processes in a sheep animal model. In contrast to previous systems, this solution combines the ability to precisely control the mechanical conditions acting within a fracture with continuous monitoring of the healing progression and autonomous operation of the system throughout the experiment. The active fixator system was implemented on a double osteotomy model that shields the experimental fracture from the influence of the animal’s functional loading. A force sensor was integrated into the fixator to continuously measure stiffness of the repair tissue as an indicator for healing progression. A dedicated control unit was developed that allows programing of different loading protocols which are later executed autonomously by the active fixator. To verify the feasibility of the system, it was implanted in two sheep with different loading protocols, mimicking immediate and delayed weight-bearing, respectively. The implanted devices operated according to the programmed protocols and delivered seamless data over the whole course of the experiment. The in vivo trial confirmed the feasibility of the system. Hence, it can be applied in further preclinical studies to better understand the influence of mechanical conditions on fracture healing.

[1]  R. Huiskes,et al.  In vivo assessment of regenerate axial stiffness in distraction osteogenesis , 2005, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[2]  D. Rosenbaum,et al.  Early, Full Weightbearing With Flexible Fixation Delays Fracture Healing , 1996, Clinical orthopaedics and related research.

[3]  L. Tagliabue,et al.  Treatment of long bone non-unions with polytherapy: indications and clinical results. , 2011, Injury.

[4]  J. Kenwright,et al.  Dynamic Interfragmentary Motion in Fractures During Routine Patient Activity , 1997, Clinical orthopaedics and related research.

[5]  P. Mendis,et al.  The relationship between interfragmentary movement and cell differentiation in early fracture healing under locking plate fixation , 2015, Australasian Physical & Engineering Sciences in Medicine.

[6]  Stephan M Perren,et al.  In vivo measurement of bending stiffness in fracture healing , 2003, Biomedical engineering online.

[7]  S. Perren,et al.  Mechanical Stimulation of Fracture Healing – Stimulation of Callus by Improved Recovery , 2019 .

[8]  M. Schuetz,et al.  Early mechanical stimulation only permits timely bone healing in sheep , 2018, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[9]  L. Claes,et al.  Early dynamization by reduced fixation stiffness does not improve fracture healing in a rat femoral osteotomy model , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

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

[11]  Ralph Müller,et al.  Mechanical Regulation of Bone Regeneration: Theories, Models, and Experiments , 2014, Front. Endocrinol..

[12]  B. Hanson,et al.  Global burden of trauma: Need for effective fracture therapies , 2009, Indian journal of orthopaedics.

[13]  J L Cunningham,et al.  Fracture stiffness measurement in the assessment and management of tibial fractures. , 1992, Clinical biomechanics.

[14]  S M Perren,et al.  The influence of cyclic compression and distraction on the healing of experimental tibial fractures , 2004, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[15]  Georg N Duda,et al.  Instability prolongs the chondral phase during bone healing in sheep. , 2006, Bone.

[16]  Lutz Claes,et al.  BMC Musculoskeletal Disorders BioMed Central Correspondence , 2007 .

[17]  P Augat,et al.  Effects of High-Frequency, Low-Magnitude Mechanical Stimulus on Bone Healing , 2001, Clinical orthopaedics and related research.

[18]  Georg N Duda,et al.  Timely fracture-healing requires optimization of axial fixation stability. , 2007, The Journal of bone and joint surgery. American volume.

[19]  Juan Antonio Gómez Galán,et al.  Real-Time Wireless Platform for In Vivo Monitoring of Bone Regeneration , 2020, Sensors.

[20]  R. G. Richards,et al.  Smart implants in fracture care - only buzzword or real opportunity? , 2020, Injury.

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

[22]  A. Goodship,et al.  Low‐magnitude high‐frequency mechanical signals accelerate and augment endochondral bone repair: Preliminary evidence of efficacy , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[23]  E Schneider,et al.  Shear Does Not Necessarily Inhibit Bone Healing , 2006, Clinical orthopaedics and related research.

[24]  M. Heller,et al.  The initial phase of fracture healing is specifically sensitive to mechanical conditions , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[25]  W. Mutschler,et al.  Monitoring and healing analysis of 100 tibial shaft fractures , 2002, Langenbeck's Archives of Surgery.

[26]  L. Claes,et al.  The effects of external mechanical stimulation on the healing of diaphyseal osteotomies fixed by flexible external fixation. , 1998, Clinical biomechanics.

[27]  R. Sanders,et al.  Invited Commentary: To Weight-Bear or Not to Weight-Bear? Is That Really a Question? , 2016, Journal of orthopaedic trauma.

[28]  S. Ferguson,et al.  Dynamization at the near cortex in locking plate osteosynthesis by means of dynamic locking screws: an experimental study of transverse tibial osteotomies in sheep. , 2015, The Journal of bone and joint surgery. American volume.

[29]  P. Giannoudis,et al.  Fracture healing: the diamond concept. , 2007, Injury.

[30]  D. Hutmacher,et al.  Monitoring Healing Progression and Characterizing the Mechanical Environment in Preclinical Models for Bone Tissue Engineering. , 2015, Tissue engineering. Part B, Reviews.

[31]  J L Cunningham,et al.  Strain Rate and Timing of Stimulation in Mechanical Modulation of Fracture Healing , 1998, Clinical orthopaedics and related research.

[32]  M. Ernst,et al.  A Biofeedback System for Continuous Monitoring of Bone Healing , 2014, BIODEVICES.

[33]  J. Domínguez,et al.  Distraction osteogenesis device to estimate the axial stiffness of the callus in Vivo. , 2015, Medical engineering & physics.

[34]  J. Cordey,et al.  Force required for bone segment transport in the treatment of large bone defects using medullary nail fixation. , 1994, Clinical orthopaedics and related research.

[35]  E Schneider,et al.  An experimental two degrees-of-freedom actuated external fixator for in vivo investigation of fracture healing. , 2003, Medical engineering & physics.

[36]  Lutz Claes,et al.  Shear movement at the fracture site delays healing in a diaphyseal fracture model , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[37]  J. P. Paul,et al.  The design and performance of an experimental external fixator with variable axial stiffness and a compressive force transducer. , 1997, Medical engineering & physics.

[38]  B. Cohen,et al.  Relative contribution of walking velocity and stepping frequency to the neural control of locomotion , 2008, Experimental Brain Research.

[39]  L. Claes,et al.  Novel systems for the application of isolated tensile, compressive, and shearing stimulation of distraction callus tissue , 2017, PloS one.

[40]  J Kenwright,et al.  The influence of induced micromovement upon the healing of experimental tibial fractures. , 1985, The Journal of bone and joint surgery. British volume.

[41]  D Kaspar,et al.  Effects of Mechanical Factors on the Fracture Healing Process , 1998, Clinical orthopaedics and related research.