Le Nihouannen Damien, Komarova Svetlana V, Gbureck Uwe, Barralet Jake E
Faculty of Dentistry, McGill University, Montreal, Que., Canada.
Eur J Pharm Biopharm. 2008 Nov;70(3):813-8. doi: 10.1016/j.ejpb.2008.07.018. Epub 2008 Aug 14.
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.
自二十年前提出磷酸钙骨水泥以来,人们开展了广泛研究以开发和改进其性能。它们已证明作为骨移植替代物的有效性以及结合和释放药物的能力。然而,迄今为止,所有“可吸收”的骨传导性合成生物材料实际上只是可溶解的。为了研究一种能够在植入后诱导破骨细胞重塑的合成材料,对负载促吸收细胞因子(RANKL)的磷酸钙骨水泥配方进行了研究。许多先前关于磷酸钙的释放研究并未证实基质在使用前储存期间对待释放分子没有有害影响,也未证实在储存期间生物活性得以维持。在本报告中,测试了我们的蛋白质负载到骨水泥上后的稳定性,并比较了各种提高稳定性的方案。结果表明,海藻糖的存在可稳定吸附在透钙磷石骨水泥上的RANKL的生物活性。与储存在环境大气和温度下相比,储存容器中水分和氧气的减少提高了基质的破骨细胞生成潜力。对于储存在干燥氮气中的负载基质,在研究期间未观察到活性损失。