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首页> 外文期刊>RSC Advances >Local delivery of a novel PTHrP via mesoporous bioactive glass scaffolds to improve bone regeneration in a rat posterolateral spinal fusion model
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Local delivery of a novel PTHrP via mesoporous bioactive glass scaffolds to improve bone regeneration in a rat posterolateral spinal fusion model

机译：通过介孔生物活性玻璃支架局部递送新型PTHrP，以改善大鼠后外侧脊柱融合模型中的骨再生

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With the development of tissue engineering, bone defects, such as fractured long bones or cavitary lesions, may be efficiently repaired and reconstructed using bone substitutes. However, high rates of fusion failure remain unavoidable in spinal fusion surgery owing to the lack of appropriate materials for bone regeneration under such challenging conditions. Parathyroid hormone (PTH), a major regulator of bone remodeling, exerts both anabolic and catabolic effects. In this study, we modified PTH(1–34) and designed and synthesized a novel PTH-related peptide, namely PTHrP-1. Further, we fabricated a local PTHrP delivery device from mesoporous bioactive glass (MBG) to address the need for a suitable material in spinal fusion surgery. Using MBG scaffolds as a control, the biological properties of PTHrP-MBG scaffolds were evaluated in terms of attachment, proliferation, and alkaline phosphatase activity, as well as osteogenic gene and angiogenic gene expression in co-cultured rat bone marrow mesenchymal stem cells (rBMSCs) in vitro . Furthermore, PTHrP-1-MBG scaffolds were tested in a rat posterolateral spinal fusion model. Our data showed that PTHrP-1-MBG scaffolds possessed good ability to facilitate attachment and stimulation of rBMSC proliferation and differentiation. Importantly, the in vivo results revealed that the PTHrP-1-MBG scaffolds facilitated faster new bone formation and a higher rate and quality of spinal fusion. Therefore, the results suggest that devices consisting of the present novel PTHrP and MBG possess wider potential applications in bone regeneration and should serve as a promising bone substitute for spinal fusion.
机译：随着组织工程学的发展，可以使用骨替代物有效地修复和重建诸如骨折的长骨或空洞病变的骨缺损。然而，由于缺乏在这种挑战性条件下进行骨再生的合适材料，在脊柱融合手术中仍然不可避免地出现高融合失败率。甲状旁腺激素（PTH）是骨骼重塑的主要调节剂，具有同化和分解代谢作用。在这项研究中，我们修饰了PTH（1-34），并设计和合成了一种新型的PTH相关肽，即PTHrP-1。此外，我们用中孔生物活性玻璃（MBG）制造了局部PTHrP输送装置，以满足脊柱融合手术中对合适材料的需求。使用MBG支架作为对照，通过共培养大鼠骨髓间充质干细胞（rBMSCs）的附着，增殖和碱性磷酸酶活性以及成骨基因和血管生成基因表达来评估PTHrP-MBG支架的生物学特性） 体外 。此外，在大鼠后外侧脊柱融合模型中测试了PTHrP-1-MBG支架。我们的数据表明，PTHrP-1-MBG支架具有促进rBMSC增殖和分化的附着和刺激的良好能力。重要的是，体内结果显示，PTHrP-1-MBG支架可促进更快的新骨形成以及更高的脊柱融合率和质量。因此，结果表明，由本发明的新型PTHrP和MBG组成的装置在骨再生中具有更广泛的潜在应用，并且应作为脊柱融合的有希望的骨替代物。

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