Heterobifunctional poly(ethylene glycol)-tethered bone morphogenetic protein-2-stimulated bone marrow mesenchymal stromal cell differentiation and osteogenesis
Heterobifunctional poly(ethylene glycol)-tethered bone morphogenetic protein-2-stimulated bone marrow mesenchymal stromal cell differentiation and osteogenesis
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DOI：
10.1089/ten.2006.0209
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发表时间：
2007-05-01
影响因子：
--
通讯作者：
Hsiue, Ging-Ho
中科院分区：
文献类型：
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作者：
Liu, Hsia-Wei;Chen, Chih-Hwa;Hsiue, Ging-Ho
我们描述了一种不溶性信号刺激的仿生模式，以提供骨形态发生蛋白-2 （BMP-2）的靶递送，目的是延长BMP-2在骨组织工程中的使用，并使其在响应细胞活动时能够局部释放。在我们新的定位过程中，我们使用异双功能丙烯酸酯- n -羟基丁二酰亚胺聚乙二醇（PEG）作为间隔剂将BMP-2系在聚丙交酯-共乙二醇酯支架上。使用聚乙二醇系缚的BMP-2是可行的，因为BMP-2在共价偶联后仍保持其活性。聚乙二醇拴系的BMP-2偶联持续刺激并保持其有丝分裂活性，显著影响多能干细胞的增殖和分化。我们将骨髓间充质间质细胞作为祖细胞植入支架，观察其形态学和表型表达。我们还建立了兔双侧全层颅骨缺损，以研究培养的间充质间质细胞对骨再生的体内成骨作用。组织形态学和组织学显示，聚乙二醇系缚的BMP-2结合物增强了手术后的新生骨形成。我们的工作揭示了通过捕获信号生长因子来刺激成骨的仿生表面工程的潜力。我们的技术可能为骨工程干细胞治疗提供一个新的平台。
We describe a biomimetic mode of insoluble signaling stimulation to provide target delivery of bone morphogenetic protein-2 (BMP-2), with the aim of prolonging the retention of BMP-2 use in bone tissue engineering and to enable its localized release in response to cellular activity. In our novel localization process, we used heterobifunctional acrylate-N-hydroxysuccinimide poly(ethylene glycol) (PEG) as a spacer to tether BMP-2 onto a poly(lactide-co-glycolide) scaffold. Use of PEG-tethered BMP-2 was feasible because BMP-2 retained its activity after covalent conjugation. The PEG-tethered BMP-2 conjugate sustained stimulation and retained its mitogenic activity, notably affecting pluripotent stem cell proliferation and differentiation. We seeded the scaffolds with bone marrow-derived mesenchymal stromal cells as progenitor cells to evaluate their morphology and phenotypic expression. We also created bilateral, fullthickness cranial defects in rabbits to investigate the osteogenic effect of cultured mesenchymal stromal cells on bone regeneration in vivo. Histomorphometry and histology demonstrated that the PEG-tethered BMP-2 conjugate enhanced de novo bone formation after surgery. Our work revealed the potential for biomimetic surface engineering by entrapping signaling growth factor to stimulate osteogenesis. Our technique may provide a new platform for bone-engineered stem cell therapies.