Liang Bo, Huang Jinghuan, Xu Jianguang, Li Xiaolin, Li Jingfeng
Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital 600 Yishan Road Shanghai 200233 PR China
Department of Orthopedics, Zhongnan Hospital of Wuhan University Wuhan 430071 PR China
RSC Adv. 2018 Apr 3;8(22):12484-12493. doi: 10.1039/c8ra00870a. eCollection 2018 Mar 26.
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) . 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 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.
随着组织工程学的发展，诸如长骨骨折或空洞性病变等骨缺损，可使用骨替代物进行有效修复和重建。然而，由于在如此具有挑战性的条件下缺乏用于骨再生的合适材料，脊柱融合手术中融合失败的高发生率仍然不可避免。甲状旁腺激素（PTH）是骨重塑的主要调节因子，具有合成代谢和分解代谢作用。在本研究中，我们对PTH(1 - 34)进行了修饰，设计并合成了一种新型的PTH相关肽，即PTHrP - 1。此外，我们用介孔生物活性玻璃（MBG）制作了一种局部PTHrP递送装置，以满足脊柱融合手术中对合适材料的需求。以MBG支架作为对照，从附着、增殖、碱性磷酸酶活性以及共培养的大鼠骨髓间充质干细胞（rBMSCs）中成骨基因和血管生成基因表达方面评估了PTHrP - MBG支架的生物学特性。此外，在大鼠后外侧脊柱融合模型中对PTHrP - 1 - MBG支架进行了测试。我们的数据表明，PTHrP - 1 - MBG支架具有促进rBMSC附着以及刺激其增殖和分化的良好能力。重要
