Temporal delimitation of the healing phases via monitoring of fracture callus stiffness in rats

Wehner, Tim; Gruchenberg, Katharina; Bindl, Ronny; Recknagel, Stefan; Steiner, Malte; Ignatius, Anita

doi:10.1002/jor.22721

Cited by 16 publications

(16 citation statements)

References 28 publications

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“…To our knowledge, this is the first study to attempt bone formation dynamics characterization during Masquelet’s second stage. Our results suggest that, similar to fracture healing, 1,6,9,16,42,55 new tissue formation occurs in a wave extending from the proximal and distal edges toward the defect center rather than extending from the membrane edges radially inward. Also like fracture healing, there is significant activity in 463 the first few weeks.…”

Section: Discussionmentioning

confidence: 59%

Masquelet Technique: Effects of Spacer Material and Micro-topography on Factor Expression and Bone Regeneration

et al. 2018

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We and others have shown that changing surface characteristics of the spacer implanted during the first Masquelet stage alters some aspects of membrane development. Previously we demonstrated that titanium spacers create membranes that are better barriers to movement of solutes >70kDa in size than polymethyl methacrylate (PMMA) induced-membranes, and roughening creates more mechanically compliant membranes. However, it is unclear if these alterations affect the membrane’s biochemical environment or bone regeneration during the second stage. Ten-week-old, male Sprague-Dawley rats underwent an initial surgery to create an externally stabilized 6mm femoral defect. PMMA or titanium spacers with smooth (~1um) or roughened (~8um) surfaces were implanted. Four weeks later, rats were either euthanized for membrane harvest or underwent the second Masquelet surgery. Titanium spacers induced thicker membranes that were similar in structure and biochemical expression. All membranes were bilayered with the inner layer having increased factor expression (BMP2, TGFβ, IL6, and VEGF). Roughening increased overall IL6 levels. Ten-weeks post-engraftment, PMMA-smooth induced membranes better supported bone regeneration (60% union). The other groups only had 1 or 2 that united (9–22%). There were no significant differences in any microCT or dynamic histology outcome. In conclusion, this study suggests that the membrane’s important function in the Masquelet technique is not simply as a barrier. There is likely a critical biochemical, cellular, or vascular component as well.

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Section: Discussionmentioning

confidence: 59%

Masquelet Technique: Effects of Spacer Material and Micro-topography on Factor Expression and Bone Regeneration

et al. 2018

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“…In another study, callus stiffness as monitored in vivo was found to determine maximum stiffness at 4 weeks with the stiff fixator, as compared to 9 weeks with the flexible fixator (Wehner et al. 2014). Thus, the stiff fixator can be considered to provide stable fixation and timely healing while the flexible fixator can be considered to be too flexible and to delay healing.…”

Section: Discussionmentioning

confidence: 99%

Modulation of fixation stiffness from flexible to stiff in a rat model of bone healing

et al. 2016

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Background and purposeConstant fixator stiffness for the duration of healing may not provide suitable mechanical conditions for all stages of bone repair. We therefore investigated the influence of stiffening fixation on callus stiffness and morphology in a rat diaphyseal osteotomy model to determine whether healing time was shortened and callus stiffness increased through modulation of fixation from flexible to stiff.Material and methodsAn external unilateral fixator was applied to the osteotomized femur and stiffened by decreasing the offset of the inner fixator bar at 3, 7, 14, and 21 days after operation. After 5 weeks, the rats were killed and healing was evaluated with mechanical, histological, and microcomputed tomography methods. Constant fixation stiffness control groups with either stiff or flexible fixation were included for comparison.ResultsThe callus stiffness of the stiff group and all 4 experimental groups was greater than in the flexible group. The callus of the flexible group was larger but contained a higher proportion of unmineralized tissue and cartilage. The stiff and modulated groups (3, 7, 14, and 21 days) all showed bony bridging at 5 weeks, as well as signs of callus remodeling. Stiffening fixation at 7 and 14 days after osteotomy produced the highest degree of callus bridging. Bone mineral density in the fracture gap was highest in animals in which the fixation was stiffened after 14 days.InterpretationThe predicted benefit of a large robust callus formed through early flexible fixation could not be shown, but the benefits of stabilizing a flexible construct to achieve timely healing were demonstrated at all time points.

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“…Several groups use constrained torsion instead [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ], which is sensitive to embedding uncertainties, especially for shifting of the specimens’ axis of gravity creating a parallel offset to the fixed measurement axis of rotation. Furthermore, bending tests are established for ex vivo mechanical testing [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Bending tests have the potential to deliver robust values of the callus stiffness, independently of embedding errors, provided that the maximum callus expansion direction is consistently oriented relative to the loading direction for all investigated specimens.…”

Section: Discussionmentioning

confidence: 99%

“…Non-destructive torsional testing is performed in rat [ 6 , 7 , 8 , 9 , 10 ] as well as in mouse experiments [ 11 , 12 , 13 , 14 ]. Bending is also performed in experiments for both species: three-point bending in rats [ 15 , 16 , 17 , 18 ] and mice [ 19 , 20 , 21 , 22 , 23 ] as well as four-point bending in rats [ 24 ] and mice [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Comparison between Different Methods for Biomechanical Assessment of Ex Vivo Fracture Callus Stiffness in Small Animal Bone Healing Studies

et al. 2015

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For ex vivo measurements of fracture callus stiffness in small animals, different test methods, such as torsion or bending tests, are established. Each method provides advantages and disadvantages, and it is still debated which of those is most sensitive to experimental conditions (i.e. specimen alignment, directional dependency, asymmetric behavior). The aim of this study was to experimentally compare six different testing methods regarding their robustness against experimental errors. Therefore, standardized specimens were created by selective laser sintering (SLS), mimicking size, directional behavior, and embedding variations of respective rat long bone specimens. For the latter, five different geometries were created which show shifted or tilted specimen alignments. The mechanical tests included three-point bending, four-point bending, cantilever bending, axial compression, constrained torsion, and unconstrained torsion. All three different bending tests showed the same principal behavior. They were highly dependent on the rotational direction of the maximum fracture callus expansion relative to the loading direction (creating experimental errors of more than 60%), however small angular deviations (<15°) were negligible. Differences in the experimental results between the bending tests originate in their respective location of maximal bending moment induction. Compared to four-point bending, three-point bending is easier to apply on small rat and mouse bones under realistic testing conditions and yields robust measurements, provided low variation of the callus shape among the tested specimens. Axial compressive testing was highly sensitive to embedding variations, and therefore cannot be recommended. Although it is experimentally difficult to realize, unconstrained torsion testing was found to be the most robust method, since it was independent of both rotational alignment and embedding uncertainties. Constrained torsional testing showed small errors (up to 16.8%, compared to corresponding alignment under unconstrained torsion) due to a parallel offset between the specimens’ axis of gravity and the torsional axis of rotation.

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Temporal delimitation of the healing phases via monitoring of fracture callus stiffness in rats

Cited by 16 publications

References 28 publications

Masquelet Technique: Effects of Spacer Material and Micro-topography on Factor Expression and Bone Regeneration

Masquelet Technique: Effects of Spacer Material and Micro-topography on Factor Expression and Bone Regeneration

Modulation of fixation stiffness from flexible to stiff in a rat model of bone healing

Comparison between Different Methods for Biomechanical Assessment of Ex Vivo Fracture Callus Stiffness in Small Animal Bone Healing Studies

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