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载有辛伐他汀的电纺螺旋缠绕聚己内酯支架在大鼠颅骨缺损修复模型中的体内性能

In vivo performance of simvastatin-loaded electrospun spiral-wound polycaprolactone scaffolds in reconstruction of cranial bone defects in the rat model.

作者信息

Pişkin Erhan, Işoğlu I Alper, Bölgen Nimet, Vargel Ibrahim, Griffiths Sarah, Cavuşoğlu Tarik, Korkusuz Petek, Güzel Elif, Cartmell Sarah

机构信息

Hacettepe University, Chemical Engineering Department and Bioengineering Division, Beytepe, Ankara, Turkey.

出版信息

J Biomed Mater Res A. 2009 Sep 15;90(4):1137-51. doi: 10.1002/jbm.a.32157.

DOI:10.1002/jbm.a.32157
PMID:18671271
Abstract

Reconstruction of large bone defects is still a major problem. Tissue-engineering approaches have become a focus in regeneration of bone. In particular, critical-sized defects do not ossify spontaneously. The use of electrospinning is attracting increasing attention in the preparation of tissue-engineering scaffolds. Recently, acellular scaffolds carrying bioactive agents have been used as scaffolds in "in situ" tissue engineering for soft and hard tissue repair. Poly(epsilon-caprolactone) (PCL) with two different molecular weights were synthesized, and the blends of these two were electrospun into nonwoven membranes composed of nanofibers/micropores. To stimulate bone formation, an active drug, "simvastatin" was loaded either after the membranes were formed or during electrospinning. The matrices were then spiral-wound to produce scaffolds with 3D-structures having both macro- and microchannels. Eight-millimeter diameter critical size cranial defects were created in rats. Scaffolds with or without simvastatin were then implanted into these defects. Samples from the implant sites were removed after 1, 3, and 6 months postimplantation. Bone regeneration and tissue response were followed by X-ray microcomputed tomography and histological analysis. These in vivo results exhibited osseous tissue integration within the implant and mineralized bone restoration of the calvarium. Both microCT and histological data clearly demonstrated that the more successful results were observed with the "simvastatin-containing PCL scaffolds," in which simvastatin was incorporated into the PCL scaffolds during electrospinning. For these samples, bone mineralization was quite significant when compared with the other groups.

摘要

大骨缺损的修复仍然是一个主要问题。组织工程方法已成为骨再生的一个焦点。特别是,临界尺寸的缺损不会自发骨化。静电纺丝在组织工程支架的制备中越来越受到关注。最近,携带生物活性剂的脱细胞支架已被用作“原位”组织工程中软组织和硬组织修复的支架。合成了两种不同分子量的聚(ε-己内酯)(PCL),并将这两种的共混物静电纺丝成由纳米纤维/微孔组成的非织造膜。为了刺激骨形成,在膜形成后或静电纺丝过程中加载活性药物“辛伐他汀”。然后将基质螺旋缠绕以生产具有宏观和微观通道的三维结构支架。在大鼠中制造直径为8毫米的临界尺寸颅骨缺损。然后将含有或不含有辛伐他汀的支架植入这些缺损中。在植入后1、3和6个月从植入部位取出样品。通过X射线微计算机断层扫描和组织学分析跟踪骨再生和组织反应。这些体内结果显示植入物内有骨组织整合以及颅骨矿化骨修复。微CT和组织学数据均清楚地表明,使用“含辛伐他汀的PCL支架”观察到的结果更成功,其中辛伐他汀在静电纺丝过程中被掺入PCL支架中。对于这些样品,与其他组相比,骨矿化相当显著。

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