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Sequential delivery of BMP-2 and IGF-1 using a chitosan gel with gelatin microspheres enhances early osteoblastic differentiation

机译:使用壳聚糖微球的壳聚糖凝胶顺序递送BMP-2和IGF-1增强了早期骨细胞分化

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摘要

The purpose of this study was to develop and characterize a chitosan gel/gelatin microsphere (MSs) dual delivery system for sequential release of bone morphogenetic protein-2 (BMP-2) and insulin-like growth factor-1 (IGF-1) to enhance osteoblast differentiation in vitro. We made and characterized the delivery system based on its degree of cross-linking, degradation, and release kinetics. We also evaluated the cytotoxicity of the delivery system and the effect of growth factors on cell response using pre-osteoblast W-20-17 mouse bone marrow stromal cells. IGF-1 was first loaded into MSs, and then the IGF-1-containing MSs were encapsulated into the chitosan gel which contained BMP-2. Cross-linking of gelatin with glyoxal via Schiff bases significantly increased thermal stability and decreased the solubility of the MSs, leading to a significant decrease in the initial release of IGF-1. Encapsulation of the MSs into the chitosan gel generated polyelectrolyte complexes by intermolecular interactions, which further affected the release kinetics of IGF-1. This combinational delivery system provided an initial release of BMP-2 followed by a slow and sustained release of IGF-1. Significantly greater alkaline phosphatase activity was found in W-20-17 cells treated with the sequential delivery system compared with other treatments (P < 0.05) after a week of culture.
机译:本研究的目的是开发和表征壳聚糖凝胶/明胶微球(MSS)双递送系统,用于释放骨形态发生蛋白-2(BMP-2)和胰岛素样生长因子-1(IGF-1)增强体外成骨细胞分化。我们基于其交联,降解和释放动力学的程度来制作并表征了交付系统。我们还评估了递送系统的细胞毒性以及使用前成骨细胞W-20-17小鼠骨髓基质细胞的细胞反应对细胞反应的影响。首先将IGF-1加载到MS中,然后将IGF-1的MS包封在含有BMP-2的壳聚糖凝胶中。通过Schiff碱基通过辛亚替辛与乙醛的交联显着提高了热稳定性并降低了MS的溶解度,导致IGF-1的初始释放的显着降低。通过分子间相互作用将MSS封装到壳聚糖凝胶中产生的聚电解质配合物,其进一步影响了IGF-1的释放动力学。该组合递送系统提供了BMP-2的初始释放,然后是IGF-1缓慢且持续释放。在用序列递送系统处理的W-20-17细胞中,与其他治疗后的其他处理(P <0.05)相比,在用序列递送系统处理的W-20-17细胞中发现了显着更大的碱性磷酸酶活性。

著录项

  • 来源
    《Acta biomaterialia》 |2012年第5期|共10页
  • 作者单位

    Department of Orthopedic Surgery Stanford University Stanford CA United States;

    Department of Orthopedic Surgery Stanford University Stanford CA United States;

    Extremity Trauma and Regenerative Medicine Task Area US Army Institute of Surgical Research San;

    Department of Orthopedic Surgery University of Texas Health Science Center at Houston Houston TX;

    Center for Translational Injury Research Department of Surgery University of Texas Health Science;

    Department of Biochemistry Rush University Medical Center Chicago IL United States;

    Extremity Trauma and Regenerative Medicine Task Area US Army Institute of Surgical Research San;

    Department of Orthopedic Surgery Stanford University Stanford CA United States;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 普通生物学;
  • 关键词

    BMP-2; Chitosan; Gelatin microspheres; Glyoxal; IGF-1;

    机译:BMP-2;壳聚糖;明胶微球;乙二醛;IGF-1;

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