Investigator: V. Viateau
Another strategy to improve bone repair consists in recruiting local osteocompetent cells (in periphery of the bone defect) via the use of bioactive factors. In that perspective, BMPs (Bone Morphogenetic Protein) are of particular interest as they are osteinductive molecules (i.e. inducing bioactive cascades leading to new bone formation) with a specific action on bone and cartilage.
In clinical practice, BMP-2 is actually use for different medical applications where new bone formation is required. It is then added in absorbable collagen sponges which will deliver the BMP2 as they get degraded. Supra-physiological doses (in the tens of milligrams range) are, however, required for such applications because of the low affinity of BMP-2 for collagen, risking unwanted side effects and raising the cost of such therapeutic to levels prohibitive for a large scale clinical use. Several collaborative projects (U1292 Biosanté in Grenoble / CBM in Orléans) aim to test new systems of controlled release of BMP (as protein or mRNA), in order to minimize the risk and the cost associated with this therapeutical strategy.
Publications of the project
Larochette N, El-Hafci H, Potier E, Setterblad N, Bensidhoum M, Petite H, Logeart-Avramoglou D. Osteogenic-differentiated mesenchymal stem cell-secreted extracellular matrix as a bone morphogenetic protein-2 delivery system for ectopic bone formation. Acta Biomater. 2020 Oct 15;116:186-200. Link for the publication .
Wang P, Logeart-Avramoglou D, Petite H, Goncalves C, Midoux P, Perche F, Pichon C. Co-delivery of NS1 and BMP2 mRNAs to murine pluripotent stem cells leads to enhanced BMP-2 expression and osteogenic differentiation. Acta Biomater. 2020 May;108:337-346. Link for the publication .
Guillot R., Gilde F., Becquart P., Sailhan F., Lapeyrere A., Logeart-Avramoglou D., Picart C. The stability of BMP loaded polyelectrolyte multilayer coatings on titanium. Biomaterials 34(23):5737-46 (2013). Link for the publication .
Decambron A, Fournet A, Bensidhoum M, Manassero M, Sailhan F, Petite H, Logeart-Avramoglou D, Viateau V. Low-dose BMP-2 and MSC dual delivery onto coral scaffold for critical-size bone defect regeneration in sheep. J Orthop Res. 35 (12): 2637-2645 (2017). Link for the publication .