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Presenter: Thomas, Schubert, Brussels, Belgium
Authors: Thomas Schubert1, Daela Xhema1,2, Gwen Beaurin1, Pierre-Yves Adnet1, Pierre Gianello1, Denis Dufrane1,2
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Pig as a large animal model for bone tissue engineering development
Thomas Schubert1, Daela Xhema1,2, Gwen Beaurin1, Pierre-Yves Adnet1, Pierre Gianello1, Denis Dufrane1,2
1Laboratory of Experimental Surgery; 2Endocrine Cell Therapy Unit, UCL - Université Catholique de Louvain, Brussels, Belgium
Introduction: Massive bone defects and non-unions remain major challenges in large animal models to demonstrate the potential of tissue engineering for clinical application. Our work investigated two surgical models developed in pigs: (i) a multi-level spinal fusion and (ii) a massive femoral bone defect to achieve a non-union at 6 months post-operation (defined as a sclerotic tissue without spontaneous bone formation for sham animals).
Material & Methods: (i) Spinal fusion (n=6): an Anterior Lumbar Interbody Fusion (ALIF) procedure was performed by lumbotomy. Empty interbody fusion cages of appropriate sizes were inserted laterally.
(ii) Femoral defect (n=2): a lateral approach provided an access to the femur in view to create a 15mm critical bone defect. Stabilization was realized by a 4.5mm titanium locking compression plate (LCP). A second LCP was positioned at 90° to the previous one, to obtain long term stability.
Animals were followed in vivo by imagery between 4 and 12 post-operative weeks (POW) with a CT scan performed at 4,8 and 12 weeks. Micro-CT-scan, histomorphometry (Hemalun-Eosin, Masson’s trichrom) and immunohistochemistry for osteocalcin and Vascular Endothelial Growth Factor (VEGF) were also performed on explanted implants.
Results: (i) Spinal fusion: CT scan (at 4, 8 and 12 POW) demonstrated no spontaneous consolidation of empty cages. This was confirmed by micro-CT (no central calcification), histology (fibrosis, lack of angiogenesis) and immunohistochemistry (low osteocalcin expression and poor secretion of VEGF).
(ii) Femoral defect: osteosynthesis failure was found (<8 POW) due to implant disruption with only one LCP plate. A bone non-union (without osteoinduction) was obtained at 7 months post-operation with two plates as confirmed by CT-scan and macroscopic disruption between bone segments.
Conclusions: Two surgical pre-clinical pig models were developed to obtain a reproducible bone non-union model in view to test different cellular and/or biocompatible implants.
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