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双重递送 PDGF 和辛伐他汀以加速体内牙周组织再生。

Dual delivery of PDGF and simvastatin to accelerate periodontal regeneration in vivo.

机构信息

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan, ROC; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan, ROC.

出版信息

Biomaterials. 2013 Dec;34(38):9990-7. doi: 10.1016/j.biomaterials.2013.09.030. Epub 2013 Sep 29.

DOI:10.1016/j.biomaterials.2013.09.030
PMID:24079892
Abstract

The emphasis on periodontal regeneration has been shifted towards the harmonization of bioactive molecules and physiological phases during regeneration. This study investigated whether the combination and sequential-release of platelet-derived growth factor (PDGF, mitogen) and simvastatin (differentiation factor) facilitated periodontal regeneration. PDGF and simvastatin were encapsulated in double-walled poly-( d,l-lactide) and poly-(d,l-lactide-co-glycolide) (PDLLA-PLGA) microspheres using the co-axial electrohydrodynamic atomization technique. Critical-sized periodontal defects on rat maxillae were filled with microspheres encapsulating BSA-in-core-shell (BB), PDGF-in-shell (XP), simvastatin-in-core and BSA-in-shell (SB), simvastatin-in-core and PDGF-in-shell, or unfilled with microspheres (XX), and examined at 14 and 28 days post-operatively. The resultant microspheres were around 15 μm diameter with distinct core-shell structure, and the fast-release of PDGF followed by slow-release of simvastatin was noted in the SP group. The SP group demonstrated significantly greater bone volume fraction and decreased trabecular separation compared to the XX group at day 14, and milder inflammatory cells infiltration and elevated tartrate-resistant acid phosphatase level were noted at day 28. Fibers were also well-aligned and obliquely inserted onto the root surface similar to native periodontal ligament with signs of cementogenesis in the SP group. In conclusion, the combination and sequential-release of PDGF-simvastatin accelerates the regeneration of the periodontal apparatus.

摘要

目前,牙周再生的重点已经转移到了生物活性分子与再生过程中的生理阶段的协调上。本研究旨在探讨血小板衍生生长因子(PDGF,有丝分裂原)和辛伐他汀(分化因子)联合及顺序释放是否有利于牙周组织再生。采用同轴静电纺丝技术,将 PDGF 和辛伐他汀包封于双层聚(DL-丙交酯)和聚(DL-丙交酯-共-乙交酯)(PDLLA-PLGA)微球中。在大鼠上颌骨临界尺寸牙周缺损中填充包封牛血清白蛋白的核壳微球(BB)、壳层包封 PDGF 的微球(XP)、壳层包封辛伐他汀和核层包封牛血清白蛋白的微球(SB)、壳层包封辛伐他汀和核层包封 PDGF 的微球(SP),或不填充微球(XX),并于术后 14 和 28 天进行检查。所得微球的直径约为 15 μm,具有明显的核壳结构,SP 组中 PDGF 快速释放,随后缓慢释放辛伐他汀。与 XX 组相比,SP 组在第 14 天具有更高的骨体积分数和更低的骨小梁分离率,在第 28 天具有更少的炎症细胞浸润和更高的耐酒石酸酸性磷酸酶水平。纤维也与天然牙周韧带相似,排列整齐并斜插入牙根表面,在 SP 组中可见有类牙骨质形成的迹象。总之,PDGF-辛伐他汀的联合及顺序释放可加速牙周附着器的再生。

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