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PURPOSE
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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: Favorable	Group 2: Unfavorable
Description	Native calvarial bone removed while creating defects for Group 1	rhBMP-2/ACS augmented bone regenerated in a favorable wound	rhBMP-2/ACS augmented bone regenerated in an unfavorable wound
Time points	N/a	6 weeks postoperatively 6 months postoperatively *12 months postoperatively	6 weeks postoperatively 6 months postoperatively 12 months postoperatively
Measurements	Biomechanical	Biomechanical Testing Computed Tomography	Biomechanical Testing Computed Tomography

* Data available January 2013
Table 2: Biomechanical Measurements

	Test	Clinical Significance
Stress at 80%	Samples were compressed by 0.1mm/min to 80% of initial thickness	Internal strength
Equilibration Stress at 80%	One hour of equilibration following compression to 80% initial thickness	Internal strength after equilibration
Strain at 1800N	Samples were compressed by 1800N	Compressibility
Tangent Modulus	Slope of stress-strain curve	Resistance to compression

Table 3: Results of Biomechanical Testing

	Stress at 80% (MPa)	Relaxation Stress (MPa)	Final Strain at 1800N	Tangent Modulus
Native	3.57±0.6	2.00±0.4	0.44±0.0	30.54±5.8
Favorable Reconstruction
6 weeks	a 0.38±0.2	a 0.19±0.1	a 0.21±0.0	a 3.62±0.9
6 months	3.96±0.8	2.44±0.5	a 0.27±0.0	29.0±6.4
Unfavorable Reconstruction
6 weeks	a 0.90 ± 0.6	a 0.49 ± 0.3	0.28±0.0	10.47±3.8
6 months	a 0.84 ± 0.2	a 0.47±0.1	a 0.23±0.0	a 7.11±2.14
12 months	a 1.23 ± 0.3	a 0.77±0.2	b 0.27±0.0	a 7.43±1.4

^a significance compared to native bone
^b p = 0.054