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Technical Briefs

In Vivo Model for Evaluating the Effects of Mechanical Stimulation on Tissue-Engineered Bone Repair

[+] Author and Article Information
Joel D. Boerckel, Kenneth M. Dupont, Angela S. P. Lin

G. W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, GA 30332

Yash M. Kolambkar

W. H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, GA 30332

Robert E. Guldberg

G. W. Woodruff School of Mechanical Engineering, and W. H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, GA 30332robert.guldberg@me.gatech.edu

J Biomech Eng 131(8), 084502 (Jul 02, 2009) (5 pages) doi:10.1115/1.3148472 History: Received October 13, 2008; Revised March 16, 2009; Published July 02, 2009

It has long been known that the bone adapts according to the local mechanical environment. To date, however, a model for studying the effects of functional mechanical loading on tissue-engineered bone repair in vivo has not yet been established. We have developed a rat femoral defect model, in which ambulatory loads are transduced through the implanted tissue-engineered construct to elucidate the role of the mechanical environment in functional restoration of a large bone defect. This model uses compliant fixation plates with integrated elastomeric segments, which allow transduction of ambulatory loads. Multiaxially and uniaxially compliant plates were characterized by mechanical testing and evaluated using in vivo pilot studies. In the first study, experimental limbs were implanted with multiaxial plates, which have a low stiffness in multiple loading modes. In the second study, experimental limbs were stabilized by a uniaxial plate, which allowed only axial deformation of the defect. X-ray scans and mechanical testing revealed that the multiaxial plates were insufficient to stabilize the defect and prevent fracture under ambulatory loads as a result of low flexural and torsional stiffness. The uniaxial plates, however, maintained integrity of the defect when implanted over a 12 week period. Postmortem microCT scans revealed a 19% increase in bone volume in the axially loaded limb compared with the contralateral standard control, and postmortem mechanical testing indicated that torsional strength and stiffness were increased 25.6- and 3.9-fold, respectively, compared with the control. Finite element modeling revealed high strain gradients in the soft tissue adjacent to the newly formed bone within the implanted construct. This study introduces an in vivo model for studying the effects of physiological mechanical loading on tissue-engineered bone repair. Preliminary results using this new in vivo model with the uniaxially compliant plate showed positive effects of load-bearing on functional defect repair.

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Copyright © 2009 by American Society of Mechanical Engineers
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Figures

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Figure 1

Fixation plate designs: (a) standard plate, (b) multiaxially compliant plate, (c) unactuated uniaxially compliant plate, and (d) actuated uniaxially compliant plate. Removal of the rigid clip actuates the uniaxial plate, allowing load transduction through the elastomer.

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Figure 2

Faxitron images of multiaxial plates. Replacement of standard plates with multiaxial plates at 8 weeks post-op resulted in failure under shear and bending loads, which precluded postmortem microCT scanning and biomechanical testing.

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Figure 3

Faxitron images of uniaxially compliant plate, actuated at week 4 post-op, and contralateral standard plate. The uniaxially compliant plate successfully maintained stability of the defect over the 12 week implantation period. Both samples achieved qualitative union.

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Figure 4

Postmortem microCT. (a) Images of center (7 mm) used for evaluation, (b) sectioned images to demonstrate internal architecture and connectivity, and (c) bone volume quantification over a constant VOI. Bone volumes were comparable for the two samples. Cut images demonstrate a more uniformly connected morphology in the uniaxial sample.

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Figure 5

Postmortem mechanical testing: (a) torsional stiffness and (b) maximum torque. Dotted lines represent average properties of age-matched intact femurs. The mechanical properties of the uniaxially loaded sample were 2460% and 293% greater than the sample fixated with the standard plate for stiffness and maximum torque, respectively.

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Figure 6

Finite element modeling: (a) microCT image of bone growth at week 4, sectioned, and (b) minimum principle strain distributions at week 4 under estimated boundary conditions at the same section. FE modeling revealed high strain gradients in the soft tissue adjacent to the newly formed bone within the implanted construct.

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