载药温敏水凝胶调节巨噬细胞M2极化促进骨质疏松骨缺损修复
Drug-loaded temperature sensitive hydrogel regulates macrophage M2 polarization to promote the repair of osteoporotic bone defects
韩晶媛 1李欣玲 1韩金煜 1吴宜橙 2吴高义3
作者信息
- 1. 佳木斯大学附属口腔医院,黑龙江 佳木斯 154002;口颌系统重建与再生全国重点实验室,国家口腔疾病临床医学研究中心,陕西省口腔生物工程工程技术中心,第四军医大学口腔医院种植科,陕西西安 710032
- 2. 联勤保障部队第960医院口腔科门诊,山东济南 250031
- 3. 佳木斯大学附属口腔医院,黑龙江 佳木斯 154002
- 折叠
摘要
目的:探究附载细胞因子温敏水凝胶对骨质疏松大鼠巨噬细胞调节作用及骨缺损部位成骨分化效果.方法:温敏水凝胶(PPP)附载β-烟酰胺单核苷酸(NMN)制备PN(PPP-NMN)水凝胶.冷冻扫描电镜观察凝胶孔隙率,试管倒置实验检测水凝胶溶胶-凝胶转变温度.双侧卵巢切除术制备大鼠骨质疏松模型.通过qRT-PCR、Western blot检测PN水凝胶对骨髓巨噬细胞极化调节作用.制备股骨缺损模型,局部注射PPP水凝胶和PN水凝胶.Micro-CT验证PN水凝胶对骨缺损部位骨修复作用.结果:PN水凝胶可以在室温25～37℃条件下实现快速的溶胶-凝胶转变效果,冷冻扫描电镜下观察凝胶内部具有规则空隙结构.qRT-PCR、Western blot结果表明PN水凝胶能够在基因、蛋白水平促进巨噬细胞M2极化.Micro-CT结果验证相对于PPP组,PN组骨密度值、骨体积分数有明显上调.结论:PN水凝胶具有良好温敏性,能够在体外调节巨噬细胞向M2极化.在体内能够促进骨组织再生,可能与PN水凝胶的免疫调节作用相关.
Abstract
AIM:To explore the polarization transformation of macrophages of osteoporosis rats and osteogenic differentiation effect of osteoporosis bone defect caused by temperature-sensitive hydrogel loaded with cytokine.METH-ODS:PN hydrogels were prepared by hydrogel(PPP)loaded with β-Nicotinamide Mononucleotide(NMN).The gel porosi-ty was observed by cryogenic scanning electron microscopy,and the sol-gel transition temperature was detected by invert-ed test tube.The osteoporosis model of rats was prepared by bilateral oophorectomy.The regulation effect of PN hydrogel on the polarization of macrophages was detected by qRT-PCR and Western blot.The femoral defect model of osteoporosis rats was prepared and PN hydrogel was injected locally.The bone repair effect of PN hydrogel was verified by Micro-CT.RESULTS:PN hydrogel can achieve rapid sol-gel transformation from room temperature(25℃ to 37℃).The gel has regu-lar void structure under cryogenic scanning electron microscope.The results of qRT-PCR and Western blot showed that PN hydrogel could promote macrophages M2 polarization at gene and protein levels.Micro-CT results verified that bone mineral density in PN group was significantly up-regulated compared with PPP group.CONCLUSION:PN hydrogel has good temperature sensitivity and can regulate the polarization of macrophages to M2 in vitro.In vivo,PN hydrogel can pro-mote bone tissue regeneration,which may be related to the immunomodulatory effect.
关键词
骨质疏松/温敏水凝胶/巨噬细胞Key words
osteoporosis/temperature-sensitive hydrogel/macrophage引用本文复制引用
基金项目
国家自然科学基金面上项目(6187012475)
出版年
2024
NETL
NSTL
万方数据