磺化聚醚醚酮-他汀缓释系统促进骨修复的作用研究  

Sulfonated PEEK-statins delivery system enhances bone repair in mice with skull defect

作　　者：吕丹[1] 孙莹霄 欧阳丽萍 李玲[1] 王鲁萍 廖赟 LYU Dan;SUN Yingxiao;OUYANG Liping;LI Ling;WANG Luping;LIAO Yun(Department of Pharmacy,Tongren Hospital,Shanghai Jiaotong University School of Medicine,Shanghai,200336,China)

机构地区：[1]上海交通大学医学院附属同仁医院药学部,上海200336

出　　处：《第三军医大学学报》2020年第19期1907-1912,共6页Journal of Third Military Medical University

基　　金：国家自然科学基金(81403029);上海市科学技术委员会面上项目(19ZR1449100)。

摘　　要：目的探索磺化聚醚醚酮(poly-ether-ether-ketone, PEEK)-他汀缓释系统对骨损伤的修复效果,及对成骨和H型血管的影响。方法建立小鼠颅骨损伤模型;构建磺化PEEK(SP)-普伐他汀(Pra)和SP-辛伐他汀(Sim)局部缓释系统;将不同浓度梯度的SP、SP-Pra 0.16 mg/mL、SP-Sim 0.55 mg/mL、SP-Sim 1.1 mg/mL、SP-Sim 2.2 mg/mL 5组材料植入小鼠颅骨骨缺损处,8周后取材,micro-CT检测样品周围骨再生情况,CD31和EMCN荧光双染分析样品周围骨特异性H型血管表达。结果磺化PEEK可实现他汀药物的有效负载。micro-CT结果显示:SP-Sim 1.1 mg/mL组及SP-Sim 0.55 mg/mL组材料植入组新骨再生厚度显著高于其他3组小鼠,未负载药物的SP组新骨再生厚度最低。免疫荧光检测发现,SP-Sim 1.1 mg/mL组小鼠植入物周围颅骨中CD31和EMCN双阳性H型血管明显可见,而SP组及SP-Pra 0.16 mg/mL组未观察到典型的H型血管。结论 SP-他汀缓释系统在实现骨再生治疗的同时可优化SP材料的成骨性能,机制可能与其对骨H型血管的保护作用相关。Objective To explore the effect of sulfonated poly-ether-ether-ketone(SPEEK)-statin delivery system on the repair of bone defect, H-type blood vessels and bone formation. Methods The mouse model of skull defect was established, SPEEK-pravastatin(SPEEK-Pra) and sulfonated SPEEK-simvastatin(SPEEK-Sim) delivery system were constructed, respectively. Then the samples with different concentration gradients(SPEEK 0.16 mg/mL, SPEEK-Pra 0.16 mg/mL, SPEEK-Sim 0.55 mg/mL, SPEEK-Sim 1.1 mg/mL, SPEEK-Sim 2.2 mg/mL) were implanted into the skull defect of mice, respectively. After 8 weeks, the skull samples were collected, and micro-CT scanning was used to observe the bone regeneration around of the defects, and CD31 and EMCN immunofluorescent staining was utilized to label H-type blood vessels. Results SPEEK can be used as a payload for statins. Micro-CT results showed that the thickness of skull were significantly larger in SPEEK-sim 1.1 mg/mL and SPEEK-sim 0.55 mg/mL groups than the other 3 groups, with that of the SPEEK group(without drug loading) lowest. Immunofluorescence assay found that the double-positive area was clearly visible in the SPEEK-sim 1.1 mg/mL group, but not observed in the SPEEK group and the SPEEK-pra 0.16 mg/mL group. Conclusion SPEEK-statin sustained-release system optimizes the osteogenic properties of SPEEK, which may be related to the protective effect of H blood vessel.

关 键 词：成骨 成血管 磺化PEEK 辛伐他汀 普伐他汀 

分 类 号：R318.08[医药卫生—生物医学工程] R681[医药卫生—基础医学]