Chou Ying-Chao, Cheng Yi-Shiun, Hsu Yung-Heng, Yu Yi-Hsun, Liu Shih-Jung
Biomaterials Lab, Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan; Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Biomaterials Lab, Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan.
Int J Nanomedicine. 2016 Mar 8;11:941-53. doi: 10.2147/IJN.S99791. eCollection 2016.
Biodegradable poly([D,L]-lactide-co-glycolide) (PLGA) nanofibrous membrane embedded with two drug-to-polymer weight ratios, namely 1:3 and 1:6, which comprised PLGA 180 mg, lidocaine 20 mg, vancomycin 20 mg, and ceftazidime 20 mg, and PLGA 360 mg, lidocaine 20 mg, vancomycin 20 mg, and ceftazidime 20 mg, respectively, was produced as an artificial periosteum in the treatment of segmental femoral fractures. The nanofibrous membrane's drug release behavior was assessed in vitro using high-performance liquid chromatography and the disk-diffusion method. A femoral segmental fracture model with intramedullary Kirschner-wire fixation was established for the in vivo rabbit activity study. Twenty-four rabbits were divided into two groups. Twelve rabbits in group A underwent femoral fracture fixation only, and 12 rabbits in group B underwent femoral fracture fixation and were administered the drug-loaded nanofibers. Radiographs obtained at 2, 6, and 12 weeks postoperatively were used to assess the bone unions. The total activity counts in animal behavior cages were also examined to evaluate the clinical performance of the rabbits. After the animals were euthanized, both femoral shafts were harvested and assessed for their torque strengths and toughness. The daily in vitro release curve for lidocaine showed that the nanofibers eluted effective levels of lidocaine for longer than 3 weeks. The bioactivity studies of vancomycin and ceftazidime showed that both antibiotics had effective and sustained bactericidal capacities for over 30 days. The findings from the in vivo animal activity study suggested that the rabbits with the artificial drug-eluting periosteum exhibited statistically increased levels of activity and better clinical performance outcomes compared with the rabbits without the artificial periosteum. In conclusion, this artificial drug-eluting periosteum may eventually be used for the treatment of open fractures.
生物可降解聚（[D,L]-丙交酯-共-乙交酯）（PLGA）纳米纤维膜，其嵌入了两种药物与聚合物的重量比，即1:3和1:6，分别由180毫克PLGA、20毫克利多卡因、20毫克万古霉素和20毫克头孢他啶，以及360毫克PLGA、20毫克利多卡因、20毫克万古霉素和20毫克头孢他啶组成，被制作成人工骨膜用于治疗股骨节段性骨折。使用高效液相色谱法和纸片扩散法在体外评估纳米纤维膜的药物释放行为。建立了髓内克氏针固定的股骨节段性骨折模型用于兔体内活性研究。24只兔子被分为两组。A组的12只兔子仅接受股骨骨折固定，B组的12只兔子接受股骨骨折固定并给予载药纳米纤维。术后2周、6周和12周获得的X线片用于评估骨愈合情况。还检查了动物行为笼中的总活动计数以评估兔子的临床性能。动物安乐死后，取出双侧股骨干并评估其扭矩强度和韧性。利多卡因的每日体外释放曲线表明，纳米纤维洗脱有效水平的利多卡因超过3周。万古霉素和头孢他啶的生物活性研究表明，两种抗生素在30多天内均具有有效且持续的杀菌能力。体内动物活性研究的结果表明，与没有人工骨膜的兔子相比，具有人工药物洗脱骨膜的兔子在统计学上表现出更高的活动水平和更好的临床性能结果。总之，这种人工药物洗脱骨膜最终可能用于治疗开放性骨折。
