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Enhanced Activation of Canonical Wnt Signaling Confers Mesoderm-Derived Parietal Bone with Similar Osteogenic and Skeletal Healing Capacity to Neural Crest-Derived Frontal Bone.经典Wnt信号通路的增强激活赋予中胚层来源的顶骨与神经嵴来源的额骨相似的成骨和骨骼愈合能力。
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Integration of multiple signaling regulates through apoptosis the differential osteogenic potential of neural crest-derived and mesoderm-derived Osteoblasts.多种信号的整合通过细胞凋亡调节神经嵴源性和中胚层源性成骨细胞的成骨潜能差异。
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Human adipose derived stromal cells heal critical size mouse calvarial defects.人脂肪来源的基质细胞可修复小鼠临界大小颅骨缺损。
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In vivo non-viral gene delivery of human vascular endothelial growth factor improves revascularisation and restoration of euglycaemia after human islet transplantation into mouse liver.经体内非病毒基因传递的人血管内皮生长因子可改善人胰岛细胞移植入小鼠肝脏后的再血管化和血糖恢复。
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支架介导的骨形态发生蛋白-2微环DNA递送在小鼠临界大小颅骨缺损模型中加速了骨修复。

Scaffold-mediated BMP-2 minicircle DNA delivery accelerated bone repair in a mouse critical-size calvarial defect model.

作者信息

Keeney Michael, Chung Michael T, Zielins Elizabeth R, Paik Kevin J, McArdle Adrian, Morrison Shane D, Ransom Ryan C, Barbhaiya Namrata, Atashroo David, Jacobson Gunilla, Zare Richard N, Longaker Michael T, Wan Derrick C, Yang Fan

机构信息

Department of Orthopaedic Surgery, Stanford University School of Medicine, Clark Center E-150, 300 Pasteur Drive, Edwards R105, MC5341, Stanford, California, 94305.

Department of Bioengineering, Stanford University School of Medicine, Clark Center E-150, 300 Pasteur Drive, Edwards R105, MC5341, Stanford, California, 94305.

出版信息

J Biomed Mater Res A. 2016 Aug;104(8):2099-107. doi: 10.1002/jbm.a.35735. Epub 2016 Jun 3.

DOI:10.1002/jbm.a.35735
PMID:27059085
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5127622/
Abstract

Scaffold-mediated gene delivery holds great promise for tissue regeneration. However, previous attempts to induce bone regeneration using scaffold-mediated non-viral gene delivery rarely resulted in satisfactory healing. We report a novel platform with sustained release of minicircle DNA (MC) from PLGA scaffolds to accelerate bone repair. MC was encapsulated inside PLGA scaffolds using supercritical CO2 , which showed prolonged release of MC. Skull-derived osteoblasts transfected with BMP-2 MC in vitro result in higher osteocalcin gene expression and mineralized bone formation. When implanted in a critical-size mouse calvarial defect, scaffolds containing luciferase MC lead to robust in situ protein production up to at least 60 days. Scaffold-mediated BMP-2 MC delivery leads to substantially accelerated bone repair as early as two weeks, which continues to progress over 12 weeks. This platform represents an efficient, long-term nonviral gene delivery system, and may be applicable for enhancing repair of a broad range of tissues types. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2099-2107, 2016.

摘要

支架介导的基因递送在组织再生方面具有巨大潜力。然而，以往使用支架介导的非病毒基因递送诱导骨再生的尝试很少能带来令人满意的愈合效果。我们报道了一种新型平台，该平台可使微型环状DNA（MC）从聚乳酸-羟基乙酸共聚物（PLGA）支架中持续释放，以加速骨修复。利用超临界二氧化碳将MC包裹在PLGA支架内部，其显示出MC的延长释放。体外转染了骨形态发生蛋白-2（BMP-2）MC的颅骨来源成骨细胞会导致更高的骨钙素基因表达和矿化骨形成。当植入临界大小的小鼠颅骨缺损处时，含有荧光素酶MC的支架可导致强大的原位蛋白产生，持续至少60天。支架介导的BMP-2 MC递送早在两周时就可显著加速骨修复，并在12周内持续进展。该平台代表了一种高效、长期的非病毒基因递送系统，可能适用于增强多种组织类型的修复。© 2016威利期刊公司。《生物医学材料研究杂志》A部分：104A：2099 - 2107，2016年。