Nantes Atlantique Universités, INSERM UMR 791, LIOAD, BP 84215, 44042 Nantes, France.
J Biomed Mater Res B Appl Biomater. 2010 Jul;94(1):89-96. doi: 10.1002/jbm.b.31628.
Synthetic calcium-deficient apatites (CDA) are structurally similar to biological apatites and are well known as chemical precursors of biphasic calcium phosphates (BCP). BCP are mixtures of hydroxyapatite and beta-tricalcium phosphate and are widely used as bone substitutes in human surgery. Bupivacaine, a local anesthetic, has been loaded onto CDA using isostatic compaction. The purpose of this study was to evaluate the in vivo performance of such a local release on pain after having previously defined the in vitro release profile of bupivacaine. CDA was loaded with 1%, 4%, and 16% of bupivacaine using an isostatic compaction process. In vitro release profile assays performed indicated the complete release of bupivacaine after 24 h. Wistar male rats received 50 mg implants of CDA associated, respectively, with 0, 1%, 4%, and 16% of bupivacaine into the distal femur. Analgesia was measured using the electronic version of the Von Frey monofilament test, assessing the inflammatory response and a neurological score. During the first postoperative days, a dose-dependent analgesic effect was observed with the bupivacaine adsorbed on the resorbable implant. This combined device system thus appears to release local anesthetic in a manner that prevents or limits postoperative pain following bone surgery. This innovative approach could be integrated into a global pain management program, for example, in the context of bone harvesting where bone reconstruction is required.
合成的缺钙磷灰石（CDA）在结构上与生物磷灰石相似，是双相磷酸钙（BCP）的化学前体。BCP 是羟基磷灰石和 β-磷酸三钙的混合物，广泛用作人类手术中的骨替代物。局部麻醉剂布比卡因已通过等静压压实装载到 CDA 上。本研究的目的是评估这种局部释放对疼痛的体内性能，此前已经定义了布比卡因的体外释放曲线。使用等静压压实工艺，将 CDA 负载 1%、4%和 16%的布比卡因。体外释放曲线分析表明，布比卡因在 24 小时后完全释放。Wistar 雄性大鼠将 50 mg 的 CDA 植入远端股骨，分别与 0、1%、4%和 16%的布比卡因结合。使用电子版 Von Frey 单丝试验测量镇痛，评估炎症反应和神经评分。在术后的最初几天，观察到布比卡因吸附在可吸收植入物上的剂量依赖性镇痛作用。因此，这种组合装置系统似乎以一种防止或限制骨手术后疼痛的方式释放局部麻醉剂。这种创新方法可以整合到全局疼痛管理方案中，例如在需要骨重建的骨采集的情况下。
