Chondroitin Sulfate Glycosaminoglycan Scaffolds for Cell and Recombinant Protein-Based Bone Regeneration
Chondroitin Sulfate Glycosaminoglycan Scaffolds for Cell and Recombinant Protein-Based Bone Regeneration
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DOI：
10.1002/sctm.18-0141
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发表时间：
2019-06-01
影响因子：
6
通讯作者：
Stice, Steven
中科院分区：
文献类型：
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作者：
Andrews, Seth;Cheng, Albert;Stice, Steven
骨形态发生蛋白2（BMP-2）负载的胶原海绵仍然是治疗自体骨移植物不足时大骨缺损的临床标准，尽管有相关的并发症。最近的努力，以否定合并症包括生物材料和基因治疗方法，以延长BMP-2的释放和活性的持续时间。在这项研究中，我们比较了胶原海绵临床标准硫酸软骨素糖胺聚糖（CS-GAG）支架作为重组人BMP-2（rhBMP-2）和rhBMP-2表达的载体，通过人BMP-2基因插入间充质干细胞（BMP-2 MSC）。我们证明了rhBMP-2从CS-GAG支架中的释放比从胶原海绵支架中的释放更长，并且从接种了BMP-2 MSC的CS-GAG凝胶中的释放更长。当用于治疗大鼠中具有挑战性的临界尺寸股骨缺损模型时，CS-GAG中的rhBMP-2和BMP-2 MSC诱导的骨形成与胶原海绵中的rhBMP-2相当，如通过骨体积、强度和刚度所测量的。我们的结论是，CS-GAG支架是一个有前途的交付车辆控制释放的rhBMP-2和介导修复的关键尺寸的节段性骨缺损。干细胞转化医学2019;8：575-585
Bone morphogenetic protein 2 (BMP-2)-loaded collagen sponges remain the clinical standard for treatment of large bone defects when there is insufficient autograft, despite associated complications. Recent efforts to negate comorbidities have included biomaterials and gene therapy approaches to extend the duration of BMP-2 release and activity. In this study, we compared the collagen sponge clinical standard to chondroitin sulfate glycosaminoglycan (CS-GAG) scaffolds as a delivery vehicle for recombinant human BMP-2 (rhBMP-2) and rhBMP-2 expression via human BMP-2 gene inserted into mesenchymal stem cells (BMP-2 MSC). We demonstrated extended release of rhBMP-2 from CS-GAG scaffolds compared to their collagen sponge counterparts, and further extended release from CS-GAG gels seeded with BMP-2 MSC. When used to treat a challenging critically sized femoral defect model in rats, both rhBMP-2 and BMP-2 MSC in CS-GAG induced comparable bone formation to the rhBMP-2 in collagen sponge, as measured by bone volume, strength, and stiffness. We conclude that CS-GAG scaffolds are a promising delivery vehicle for controlling the release of rhBMP-2 and to mediate the repair of critically sized segmental bone defects. Stem Cells Translational Medicine 2019;8:575-585