Dual‐Controlled Release of Icariin/Mg2+ from Biodegradable Microspheres and Their Synergistic Upregulation Effect on Bone Regeneration
Dual‐Controlled Release of Icariin/Mg2+ from Biodegradable Microspheres and Their Synergistic Upregulation Effect on Bone Regeneration
复制标题
DOI：
10.1002/adhm.202000211
复制
发表时间：
2020-04
影响因子：
10
通讯作者：
Zuoying Yuan;Zhuo Wan;Pengfei Wei;Xin Lu;Jianping Mao;Q. Cai;Xu Zhang;Xiaoping Yang
中科院分区：
文献类型：
--
作者：
Zuoying Yuan;Zhuo Wan;Pengfei Wei;Xin Lu;Jianping Mao;Q. Cai;Xu Zhang;Xiaoping Yang
目前应用于骨组织工程的支架材料仍缺乏足够的成骨能力来诱导高效的骨再生。生物可降解微球型支架是为了实现中药(淫羊藿苷，ICA)和生物活性离子(镁离子)的双重控制释放，以达到诱导成骨的协同作用。将疏水淫羊藿苷以不同的质量比预载于氧化镁/碳酸镁(质量比为1：1)微粒上，以一定比例(20wt%)将微粒包裹成可生物降解的聚丙交酯-乙交酯共聚物(PLGA)微球。检测到微球中镁离子和淫羊藿苷的持续释放，显示出对淫羊藿苷含量的依赖关系。在优化的适度负载量下，所得到的PMI-M微球在所有设计中对细胞生物学行为的激活效果最强。通过将PMI-M微球植入大鼠颅骨缺损区16周，发现其能有效促进新骨形成，其诱导成骨能力明显高于PMG(含镁/碳酸镁但不含淫羊藿苷)和空白PLGA微球。显然，释放的镁离子有利于成骨，而淫羊藿苷的共掺在诱导新骨形成方面起补充作用，这表明通过设计双释放系统来再生严重的骨损伤是一种有前途的策略。
Current scaffolds applied for bone tissue engineering are still lacking sufficient osteogenic capacity to induce efficient bone regeneration. Biodegradable microsphere‐type scaffolds are designed to achieve the dual‐controlled release of a Chinese medicine (i.e., icariin, ICA) and a bioactive ion (i.e., Mg2+), in order to achieve their synergistic effect on inducing osteogenesis. The hydrophobic icariin is preloaded onto MgO/MgCO3 (1:1 in weight ratio) particles at different amounts and then the particles are encapsulated into biodegradable poly(lactide‐co‐glycolide) (PLGA) microspheres (PMI) at a fixed fraction (20 wt%). Continuous releases of Mg2+ ion and icariin from the microspheres are detected, showing dependence on icariin amounts. At an optimized moderate loading amount, the resulting PMI‐M microspheres display the strongest activation effect on cell biological behaviors among all the designs. By implanting the PMI‐M microspheres into rat calvarial defects for 16 weeks, it is found that they can effectively enhance new bone formation, presenting significantly higher capacity in inducing osteogenesis than PMg (containing MgO/MgCO3 but without icariin) and blank PLGA microspheres. Clearly, the released Mg2+ ions are beneficial to osteogenesis, and the coincorporation of icariin exerts supplemental effects in inducing new bone formation, which suggest a promising strategy to regenerate severe bone injuries by designing a dual‐release system.