Uniform-sized insulin-loaded PLGA microspheres for improved early-stage peri-implant bone regeneration

Uniform-sized insulin-loaded PLGA microspheres for improved early-stage peri-implant bone regeneration
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大小均匀的装载胰岛素的 PLGA 微球可改善早期种植体周围骨再生

DOI:
10.1080/10717544.2019.1682719
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发表时间:
2019-01
期刊:
影响因子:
6
通讯作者:
Ren Xiuyun
Ren Xiuyun
中科院分区:
医学2区
文献类型:
--
作者:
Wang Xing;Qi Feng;Xing Helin;Zhang Xiaoxuan;Lu Chunxiang;Zheng Jiajia;Ren Xiuyun

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摘要 术后前 4 周初始稳定性差已成为金属种植体失败的主要原因。之前的尝试忽略了控制胰岛素释放以促进非糖尿病受试者的骨再生。主要原因可能是胰岛素过量引起的骨形成减弱、低血糖或高胰岛素血症等不良反应。因此,胰岛素的时空释放可能是一种有前途的策略。为了解决这个问题,我们通过溶剂萃取(EMS)、溶剂蒸发(SMS)和共溶剂法(CMS)制备了三种内部结构不同但尺寸分布相似的PLGA微球。研究了制备方法对微球性能的影响,如释放行为、分子量降低和结构演化。分别使用人骨髓间充质基质细胞(BMSC)和兔植入模型来测试微球的体外和体内生物活性。结果表明,这三种制备方法并不影响聚合物的降解,而是影响内部结构的演化,这在释放行为、成骨和种植体周围骨再生中起着至关重要的作用。与EMS和CMS微球相比,SMS微球在前4周表现出相对稳定的释放速率,明显刺激干细胞的成骨分化和种植体周围骨再生。同时,SMS微球在第4周显着增强了植入物的稳定性,这有望降低植入物的早期失败率,而不会对血清生化指标产生不良影响。
Abstract Poor initial stability at the first four weeks after surgery is becoming the major causes for metal implant failure. Previous attempts neglected the control release of insulin for the bone regeneration among nondiabetic subjects. The major reason may lie in the adverse effects, such as attenuated bone formation, hypoglycemia or hyperinsulinemia, that caused by the excessive insulin. Thus, spatiotemporal release of insulin may serve as the promising strategy. To address this, through solvent extraction (EMS), solvent evaporation (SMS) and cosolvent methods (CMS), we prepared three types of PLGA microspheres with various internal structures, but similar size distribution. The effects of the preparation methods on the properties of the microspheres, such as their release behavior, degradation of molecular weight, and structural evolution, were investigated. Human bone marrow mesenchymal stromal cells (BMSCs) and rabbit implant models were used to test the bioactivity of the microspheres in vitro and in vivo, respectively. The result demonstrated that these three preparation methods did not influence the polymer degradation but instead affected the internal structural evolution, which plays a crucial role in the release behavior, osteogenesis and peri-implant bone regeneration. Compared with EMS and CMS microspheres, SMS microspheres exhibited a relatively steady release rate in the first four weeks, which evidently stimulated the osteogenic differentiation of the stem cells and peri-implant bone regeneration. Meanwhile, SMS microspheres significantly enhanced the stability of the implant at Week 4, which is promising to reduce early failure rate of the implant without inducing adverse effects on the serum biochemical indices.
DOI: 10.1139/bcb-2013-0043
发表时间: 2013-09
期刊: Biochemistry and cell biology = Biochimie et biologie cellulaire
影响因子: --
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