Adipose-Derived Stem Cells and BMP-2 Delivery in Chitosan-Based 3D Constructs to Enhance Bone Regeneration in a Rat Mandibular Defect Model
Adipose-Derived Stem Cells and BMP-2 Delivery in Chitosan-Based 3D Constructs to Enhance Bone Regeneration in a Rat Mandibular Defect Model
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DOI：
10.1089/ten.tea.2013.0523
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发表时间：
2014-08-01
影响因子：
4.1
通讯作者：
Lee, Min
中科院分区：
文献类型：
--
作者：
Fan, Jiabing;Park, Hyejin;Lee, Min
下颌骨节段性缺损的修复一直是临床上的难题。组织工程策略为解决这一问题提供了另一种选择。本研究的目的是确定脂肪来源的干细胞（ASCs）和骨形态发生蛋白-2（BMP-2）在三维（3D）支架中对小动物模型下颌骨修复的影响。通过慢病毒短发夹RNA策略下调ASC中的Noggin表达水平以增强ASC成骨（ASC（Nog-））。壳聚糖（CH）和硫酸软骨素（CS），天然多糖，制成三维多孔支架，其进一步修饰与磷灰石涂层，以增强细胞反应和BMP-2的有效递送。在大鼠临界尺寸下颌骨缺损模型中评价了补充有ASC（Nog-）和BMP-2的3D磷灰石涂层CH/CS支架的功效。植入8周后，与单独用ASC（Nog-）或BMP-2处理的组相比，用ASC（Nog-）和BMP-2处理的支架显著促进大鼠下颌骨再生，如通过显微计算机断层扫描、组织学和免疫组织化学所证明的。这些结果表明，我们的组合策略ASCs（Nog-）+ BMP-2在三维磷灰石微环境中可以显着促进下颌骨再生，这些可能提供一个潜在的组织工程方法来修复大的骨缺损。
Reconstructing segmental mandiblular defects remains a challenge in the clinic. Tissue engineering strategies provide an alternative option to resolve this problem. The objective of the present study was to determine the effects of adipose-derived stem cells (ASCs) and bone morphogenetic proteins-2 (BMP-2) in three-dimensional (3D) scaffolds on mandibular repair in a small animal model. Noggin expression levels in ASCs were downregulated by a lentiviral short hairpin RNA strategy to enhance ASC osteogenesis (ASCs(Nog-)). Chitosan (CH) and chondroitin sulfate (CS), natural polysaccharides, were fabricated into 3D porous scaffolds, which were further modified with apatite coatings for enhanced cellular responses and efficient delivery of BMP-2. The efficacy of 3D apatite-coated CH/CS scaffolds supplemented with ASCs(Nog-) and BMP-2 were evaluated in a rat critical-sized mandibular defect model. After 8 weeks postimplantation, the scaffolds treated with ASCs(Nog-) and BMP-2 significantly promoted rat mandibular regeneration as demonstrated by micro-computerized tomography, histology, and immunohistochemistry, compared with the groups treated with ASCs(Nog-) or BMP-2 alone. These results suggest that our combinatorial strategy of ASCs(Nog-) + BMP-2 in 3D apatite microenvironments can significantly promote mandibular regeneration, and these may provide a potential tissue engineering approach to repair large bony defects.