Abstract: 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.

Key words: 20(S)-Hydroxycholesterol, polymer micelle, critical-sized bone defect, osteogenesis