载20(S)-羟基胆固醇mPEG-PLA聚合物胶束促进骨再生的效果评价  

Evaluation of 20(S)-Hydroxycholesterol loaded mPEG-PLA polymeric micelles for bone tissue regeneration

作　　者：张琪[1] 苏盈盈 王昊[1] ZHANG Qi;SU Yingying;WANG Hao(Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China)

机构地区：[1]首都医科大学附属北京天坛医院口腔科,北京100070

出　　处：《口腔生物医学》2022年第2期73-78,共6页Oral Biomedicine

基　　金：国家自然科学基金(81600829)。

摘　　要：目的:观察20(S)-羟基胆固醇(20(S)-OXY)经聚乙二醇-聚乳酸嵌段共聚物(mPEG-PLA)胶束包载后对兔颅骨缺损处新骨形成的影响。方法:制备兔颅骨骨缺损动物模型,将其随机分为4组:空载明胶海绵组、明胶海绵载空胶束组、明胶海绵载游离1000μg 20(S)-OXY,20(S)-OXY(游离组)、明胶海绵载1000μg 20(S)-OXY载药纳米胶束组(胶束包载组)。术后愈合3、6周,利用Micro-CT三维重建骨缺损区并测量新骨骨矿化密度(BMD)和相对骨体积分数(BV/TV),荧光染色标记新骨,甲苯胺蓝组织形态学观察骨缺损区新骨生成情况并测量新骨面积。结果:术后第3周和6周时,与空载明胶海绵组、明胶海绵载空胶束组相比,游离组和胶束包载组的BMD及BV/TV均显著增多(P<0.05)。空载明胶海绵组、明胶海绵载空胶束组和游离组的类骨质位于新生骨组织周围向缺损中心侧,而胶束包载组骨缺损中心出现了与骨创周围新骨不相连续的新生骨组织。结论:载20(S)-OXY mPEG-PLA胶束原位骨激活能力较游离型20(S)-OXY强,能更好促进新骨形成。Objective: To observe the effect of 20(S)-hydroxycholesterol(20(S)-OXY) loaded mPEG-PLA polymeric micelles on the osteogenesis effect in the rabbit calvarial defect.Methods: The critical-sized rabbit calvarial defect model was constructed. The experiment was randomly divided into 4 groups, namely gelatin sponge group, empty micelles group(unloaded mPEG-PLA micelles),free drug group(1 000 μg free 20(S)-OXY), drug loaded micelles group(polymeric micelle systerm containing 1 000 μg 20(S)-OXY), the last three groups were with the gelatin sponge as the carrier. Rabbits were sacrificed at 3th and 6th weeks after operation.Using Micro-CT to three-dimensionally reconstruct the bone defects and measure the new bone mineral density and volume fraction. Fluorescence staining labeled the newly formed bone tissue. Toluidine blue staining was performed to observe the histomorphology of new bone formation and measure the new bone area.Results: At 3th and 6th weeks,there was more new bone formation in free drug group and drug loaded micelles group compared with that in gelatin sponge group and empty micelles group through the morphological observation and quantitative analysis(P<0.05).The new bone tissue of gelatin sponge group, empty micelles group and free drug group was mainly located around the bone wound and pointed to the defect center, while the new bone tissue discontinuous with the bone wound also appeared in the defect center of drug loaded micelles group.Conclusions: The osteogenic induction ability of 20(S)-OXY loaded mPEG-PLA polymeric micelles in situ was better than that of free 20(S)-OXY. The new drug carrier of 20(S)-hydroxycholesterol could better promote the formation of new bone.

关 键 词：20(S)-羟基胆固醇 胶束 临界骨缺损 骨生成 

分 类 号：R783.4[医药卫生—口腔医学]