The effect of a single injection of uniform-sized insulin-loaded PLGA microspheres on peri-implant bone formation.
The effect of a single injection of uniform-sized insulin-loaded PLGA microspheres on peri-implant bone formation.
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单次注射均匀大小的胰岛素负载PLGA微球对种植体周围骨形成的影响
DOI：
10.1039/c8ra08505f
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发表时间：
2018-11-28
期刊：
影响因子：
3.9
通讯作者：
Zhao, Jing
中科院分区：
文献类型：
--
作者：
Wang, Xing;Wang, Lu;Qi, Feng;Zhao, Jing
钛植入物是广泛使用的治疗方式，在骨科、矫形外科和颌面外科中取得了一长串临床成功。然而，4.4%的患者发生早期种植体丢失，为了克服这个问题，生物活性因子通常用于改善种植体周围骨形成。最近，胰岛素在改善骨发育和生理方面的作用引起了相当大的关注。然而，由于胰岛素的快速代谢和不稳定性，一次注射胰岛素不能在骨形成部位产生持续作用，导致疗效有限。此外，微球的较宽尺寸分布经常导致胰岛素释放不可控，这影响制备的可重复性、药物功效和可靠性。在此，我们开发了尺寸均匀的负载胰岛素的聚（dl-乳酸-共-乙醇酸）（PLGA）微球，用于注射到金属植入物周围。结果表明，微球粒径分布窄（Span < 0.7），生物活性胰岛素可持续释放45天以上。该微球具有良好的促进人骨髓间充质干细胞（BMSCs）增殖的生物活性。胰岛素负载PLGA组ALP、OCN表达及矿化基质形成均显著高于其他组。此外，在兔下颌骨模型中，在钛种植体周围单次注射负载胰岛素的PLGA微球显示更高的种植体周围骨形成和更好的骨结合，如通过组织学分析、micro-CT和生物力学观察到的。
Titanium implants are widely used treatment modalities, with a long list of clinical successes in orthopaedics, orthopedics and maxillofacial surgery. However, early implant loss occurs in 4.4% of patients, and to overcome this issue, bioactive factors have been generally used for improving peri-implant bone formation. Recently, the role of insulin in the improvement of bone development and physiology has attracted considerable attention. Nevertheless, one injection of insulin could not have a persistent effect in the site for bone formation because of its fast metabolism and instability, leading to limited efficacy. Moreover, the wider size distribution of microspheres frequently leads to uncontrollable insulin release, which affects preparation repeatability, drug efficacy and reliability. Herein, we developed uniform-sized insulin-loaded poly(dl-lactic-co-glycolic acid) (PLGA) microspheres for injection around the metal implant. The results demonstrated that the microspheres had narrow size distribution (Span < 0.7) and bioactive insulin was sustainedly released from the microspheres over 45 days. These insulin-loaded PLGA microspheres exhibit good bioactivity to facilitate the proliferation of human bone marrow mesenchymal stromal cells (BMSCs). Expressions of ALP, OCN and mineralized matrix formations in the insulin-loaded PLGA group were significantly higher than those in other groups. Furthermore, in rabbit mandible models, a single injection of insulin-loaded PLGA microspheres around the titanium implant showed higher peri-implant bone formation and better osseointegration, as observed by histological analysis, micro-CT and biomechanics.
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影响因子：
64.5
作者：
Ferron M;Wei J;Yoshizawa T;Del Fattore A;DePinho RA;Teti A;Ducy P;Karsenty G
通讯作者：
Karsenty G
影响因子：
7.6
作者：
Derks, J.;Schaller, D.;Berglundh, T.
通讯作者：
Berglundh, T.
影响因子：
5.8
作者：
Qi, Feng;Wu, Jie;Su, Zhiguo
通讯作者：
Su, Zhiguo
影响因子：
64.5
作者：
Fulzele K;Riddle RC;DiGirolamo DJ;Cao X;Wan C;Chen D;Faugere MC;Aja S;Hussain MA;Brüning JC;Clemens TL
通讯作者：
Clemens TL
影响因子：
4.9
作者：
Malekzadeh, B.;Tengvall, P.;Westerlund, A.
通讯作者：
Westerlund, A.