Human Bone Marrow-Derived Mesenchymal Stromal Cell-Seeded Bone Biomaterial Directs Fast and Superior Mandibular Bone Augmentation in Rats

Atrophic maxillary ridges present a challenge in the field of oral implantology. Autologous bone is still considered the gold standard grafting material, but the increased morbidity and surgical complications represent a major drawback for its use. The aim of this study was to assess the efficacy of an off-the-shelf cell-seeded bone biomaterial for mandibular bone augmentation, compared to its acellular counterpart. We used a rat model to test the osteogenic properties of bone marrow-derived mesenchymal stromal cells (MSCs)-seeded bone microparticles compared to acellular bone microparticles alone. Rats were euthanized at 4 and 8 weeks, and results analyzed using micro-CT imaging, histology (H&E, Masson's Trichrome), histomorphometry and immunohistology (Tartrate-Resistant Acid Phosphatase-TRAP, Osteocalcin and human specific anti-mitochondria antibodies). Micro-CT analysis demonstrated that the cell-seeded biomaterial achieved significantly more bone volume formation at 4 weeks (22.75 +/- 2.25 mm(3) vs 12.34 +/- 2.91 mm(3), p = 0.016) and at 8 weeks (64.95 +/- 5.41 mm(3) vs 42.73 +/- 10.58 mm(3), p = 0.029), compared to the acellular bone microparticles. Histology confirmed that the cell-seeded biomaterial was almost completely substituted at 8 weeks, in opposition to the acellular biomaterial group. Immunohistochemical analysis showed a significantly higher number of TRAP and Osteocalcin positive cells at 4 weeks in the cell-seeded group compared to the acellular group, thereby demonstrating a higher rate of bone remodeling in the presence of MSCs. The grafted human cells remained viable and were detected up to at least 8 weeks, as observed using the human specific anti-mitochondria antibody. This off-the-shelf material available in unlimited quantities could therefore represent a significant advance in the field of mandibular bone augmentation by providing a larger volume of new bone formation in a shorter time.