Exos-ADSCs-nHAC/PLGA组织工程骨对大鼠颅骨缺损修复的实验研究

Study on Exos-ADSCs-nHAC/PLGA tissue engineering bone model in the repair of skull defects in rat

目的探索大鼠脂肪来源干细胞(adipose-derived stem cells,ADSCs)来源外泌体(exosomes,Exos)联合ADSCs负载于纳米羟基磷灰石/胶原/聚乳酸-羟基乙酸共聚物(nHAC/PLGA)支架对大鼠颅骨缺损修复的作用。方法自2020年6月至2021年1月,结合以上三者,中国医科大学附属第一医院整形外科建立SD大鼠双侧颅骨直径8 mm缺损模型,随机分为空白对照组、n HAC/PLGA支架组、ADSCs支架组、Exos-ADSCs支架组,其中,空白组和nHAC/PLGA支架组分别放置于大鼠矢状缝两侧缺损处,共10只;ADSCs支架组与Exos-ADSCs支架组分别置于大鼠颅骨矢状缝两侧,共10只。各组大鼠分别于术后4、12周取材制备标本,行大体观察及影像学和组织学检测。结果通过大体观察及影像学分析和组织学分析发现,Exos-ADSCs组支架在新骨生成质量、成骨速度、血管长入等情况均优于nHAC/PLGA和ADSCs支架组(P<0.05)。结论经Exos处理过的ADSCs在大鼠颅骨缺损实验显示出良好的成骨作用,有望成为临床中治疗骨缺损修复的新方法。

Objective To explore the effect of nHAC/PLGA scaffolds loaded with exosomes(Exos)derived from rat adipose-derived stem cells(ADSCs)combined with ADSCs in the repair of skull defects in rats.Methods The bilateral skull model with 8 mm defects was established in SD rats.All rats were randomly assigned to blank control group,nHAC/PLGA scaffolds group,ADSCs scaffolds group and Exos-ADSCs scaffolds group.In the blank group and nHAC/PLGA scaffolds group,the scaffolds were placed at the defects on both sides of sagittal suture,with a total of 10 rats.In the ADSCs scaffolds group and the Exos-ADSCs scaffolds group,the scaffolds were placed on both sides of sagittal suture of the skull,with a total of 10 rats.The rats in each group were killed at 4 and 12 weeks.The samples were collected for gross observation,imaging and histological detection.Results The gross observation,imaging and histological analysis showed that the quality of new bone formation,osteogenic speed and vessel growth in the Exos-ADSCs scaffolds group were better thanthose in the other groups.The difference was statistically significant(P<0.05).Conclusion The ADSCs treated by Exos showed good osteogenic effect in the experiment of skull defects in rats.This method is expected to be a newway in the repair of bone defects in clinic.