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Long-term Biomechanical Properties of Bone Morphogenetic Protein Regenerated Bone in Favorable and Unfavorable Calvarial Wounds
Zoe M. MacIsaac, MD1, Sarah E. Henderson, BS1, Harry S. Nayar, MBE1, Sameer Shakir, BS1, Sanjay Naran, MD1, Darren M. Smith, MD1, James Cray, PhD2, Mark Mooney, PhD1, Gregory M. Cooper, PhD1, Alejandro J. Almarza, PhD1, Joseph E. Losee, MD1.
1University of Pittsburgh, Pittsburgh, PA, USA, 2Georgia Health Sciences University, Augusta, GA, USA.

The limitations of autologous and alloplastic reconstruction for craniofacial defects have created a clinical need for viable tissue engineering strategies. Recombinant human bone morphogenetic protein-2 (rhBMP-2) has shown promise in this setting. However, while rhBMP-2 augmented reconstruction produces acceptable radiographic coverage, we predict that the biomechanical properties of the regenerate, which have yet to be investigated, differ depending on wound environment.
12-week old mature New Zealand white rabbits underwent subtotal calvariectomy. In Group 1 (Favorable), immediate skull reconstruction was performed with rhBMP-2 on an absorbable collagen sponge (rhBMP-2/ACS) in a favorable non-compromised wound. In Group 2 (Unfavorable), calvariectomy bone flaps were inoculated with S. aureus and immediately replaced orthotopically. After 2 weeks of infection, bone flaps were discarded, wounds were debrided, and antibiotic treatment instituted. Following a 6-week recovery, final debridement/reconstruction with rhBMP-2/ACS was performed. Calvarial defect percent healing was reported from 3D CT scans.
Biomechanical analysis with an unconfined compression test was performed on three groups of bone (Table 1). Samples were compressed at 0.1mm/min to 80% of initial thickness, followed by 1-hour equilibration at 80% of initial thickness, then compression by 1800N. Results were normalized (Table 2) and compared by 1-way ANOVA.
Compared to week 0, 97.7% healing in favorable reconstructions and 95.0% healing in unfavorable reconstructions were noted by 6 months postoperatively. At 12 months post-reconstruction, 98.8% healing was achieved in unfavorable defects.
Results of biomechanical testing are reported in Table 3. At 6 weeks, bone from favorable reconstruction had less internal strength, and was more compressible than native bone. By 6 months, bone from favorable reconstruction improved such that it had equivalent internal strength compared to native bone, although it remained significantly more compressible.
Bone resulting from unfavorable reconstruction had less internal strength compared to native bone at 6 weeks. At 6 months bone from unfavorable reconstruction had less internal strength and was more compressible compared to native bone. Biomechanical measures in this group did not improve between 6 and 12 months postoperatively.
Despite providing radiographic coverage, the biophysical properties of rhBMP-2 regenerated bone differ significantly from native bone. Bone generated in a favorable wound remained more compressible through 6 months postoperatively, while bone generated in an unfavorable environment was more compressible and had less internal strength at 6 months and 12 months. Further studies are warranted to determine how these properties affect overall strength and structural integrity.
Table 1: Study Groups
Native bone (control)Group 1: FavorableGroup 2: Unfavorable
DescriptionNative calvarial bone removed while creating defects for Group 1rhBMP-2/ACS augmented bone regenerated in a favorable woundrhBMP-2/ACS augmented bone regenerated in an unfavorable wound
Time pointsN/a6 weeks postoperatively
6 months postoperatively
*12 months postoperatively
6 weeks postoperatively
6 months postoperatively
12 months postoperatively
MeasurementsBiomechanicalBiomechanical Testing
Computed Tomography
Biomechanical Testing
Computed Tomography

* Data available January 2013
Table 2: Biomechanical Measurements
TestClinical Significance
Stress at 80%Samples were compressed by 0.1mm/min to 80% of initial thicknessInternal strength
Equilibration Stress at 80%One hour of equilibration following compression to 80% initial thicknessInternal strength after equilibration
Strain at 1800NSamples were compressed by 1800NCompressibility
Tangent ModulusSlope of stress-strain curveResistance to compression

Table 3: Results of Biomechanical Testing
Stress at 80% (MPa)Relaxation Stress (MPa)Final Strain at 1800NTangent Modulus
Favorable Reconstruction
6 weeksa 0.38±0.2a 0.19±0.1a 0.21±0.0a 3.62±0.9
6 months3.96±0.82.44±0.5a 0.27±0.029.0±6.4
Unfavorable Reconstruction
6 weeksa 0.90 ± 0.6a 0.49 ± 0.30.28±0.010.47±3.8
6 monthsa 0.84 ± 0.2a 0.47±0.1a 0.23±0.0a 7.11±2.14
12 monthsa 1.23 ± 0.3a 0.77±0.2b 0.27±0.0a 7.43±1.4

a significance compared to native bone
b p = 0.054

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