Bioactivity of bone resorptive factor loaded on osteoconductive matrices: Stability post-dehydration

• DOI: 10.1016/j.ejpb.2008.07.018
• Publication Date: 2008-08-15T11:00:18Z
• Authors: Damien Le Nihouannen; Svetlana V. Komarova; Uwe Gbureck; Jake E. Barralet
• Keywords: Calcium Phosphates; 0303 health sciences; Bone Regeneration; Light; Protein Stability; Chemistry, Pharmaceutical; Drug Compounding; Drug Storage; RANK Ligand; Bone Cements; Osteoclasts; Humidity; Monocytes; Cell Line; Excipients; Oxygen; Mice; 03 medical and health sciences; Solubility; Delayed-Action Preparations; Absorbable Implants; Animals

Since calcium phosphate cements were proposed two decades ago, extensive research has been realized to develop and improve their properties. They have proved their efficiency as bone graft substitutes and their ability to incorporate and release drugs. However, to date, all 'resorbable' osteoconductive synthetic biomaterials are in fact simply soluble. In order to investigate a synthetic material capable of inducing osteoclast remodelling post-implantation, a formulation of calcium phosphate cement loaded with a pro-resorptive cytokine (RANKL) was studied. Many prior release studies on calcium phosphates did not confirm that the matrix had no detrimental effect on the molecule to be released during storage prior to use or that bioactivity was maintained during storage. In this report, the stability of our protein was tested after loading onto the cement, and various regimens to improve stability were compared. The presence of trehalose was shown to stabilize the bioactivity of RANKL adsorbed to brushite cement. The reduction of both moisture and oxygen in the storage vessel improved osteoclastogenic potential of the matrix compared with that stored in ambient atmosphere and temperature. No loss in activity was observed over the study period for the loaded matrix stored in dry nitrogen.