Localization and promotion of recombinant human bone morphogenetic protein-2 bioactivity on extracellular matrix mimetic chondroitin sulfate-functionalized calcium phosphate cement scaffolds
Localization and promotion of recombinant human bone morphogenetic protein-2 bioactivity on extracellular matrix mimetic chondroitin sulfate-functionalized calcium phosphate cement scaffolds
复制标题
重组人骨形态发生蛋白2在细胞外基质模拟硫酸软骨素功能化磷酸钙水泥支架上的定位和生物活性促进
DOI：
10.1016/j.actbio.2018.01.004
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发表时间：
2018-04-15
影响因子：
9.7
通讯作者：
Liu, Changsheng
中科院分区：
文献类型：
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作者：
Huang, Baolin;Wu, Zihan;Liu, Changsheng
重组人骨形态发生蛋白-2（rhBMP-2）的定位及持续有效的成骨刺激仍是骨再生领域的一大挑战。为了实现这一目标，rhBMP-2通过特定的非共价相互作用拴在硫酸软骨素（CS）功能化磷酸钙骨水泥（CPC）支架上。将核心糖胺聚糖CS在聚多巴胺（polydopamine，PDA）的辅助下共价结合到CPC支架上，进而以仿生形式固定化rhBMP-2。CPC-PDA-CS支架不仅能控制rhBMP-2的释放动力学和呈递状态，还能有效提高骨形态发生蛋白受体（BMPRs）的表达水平，增强剩余rhBMP-2向BMPRs的转化。值得注意的是，负载rhBMP-2的CPC-PDA-CS显著促进BMPRs（尤其是BMPR-IA）的细胞表面移位。体内实验表明，与CPC和CPC-PDA相比，CPC-PDA-CS具有缓释作用，诱导高质量异位成骨。总的来说，这些结果表明，rhBMP-2可以定位在CS功能化CPC支架内，并发挥连续，长期和有效的成骨刺激。因此，这项工作可以提供新的途径，在模拟骨细胞外基质微环境和定位生长因子的活性，以促进骨再生。(C)2018 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Localization of recombinant human bone morphogenetic protein-2 (rhBMP-2) with continuous and effective osteogenic stimulation is still a great challenge in the field of bone regeneration. To achieve this aim, rhBMP-2 was tethered on chondroitin sulfate (CS)-functionalized calcium phosphate cement (CPC) scaffolds through specific noncovalent interactions. CS, one of the core glycosaminoglycans, was covalently conjugated onto CPC scaffolds with the assistance of polydopamine (PDA) and further immobilized rhBMP-2 in a biomimetic form. The CPC-PDA-CS scaffolds not only controlled the release kinetics and presentation state of rhBMP-2 but also effectively increased the expression levels of bone morphogenetic protein receptors (BMPRs) and enhanced the recognitions of the remaining rhBMP-2 to BMPRs. Strikingly, the rhBMP-2-loaded CPC-PDA-CS significantly promoted the cellular surface translocation of BMPRs (especially BMPR-IA). In vivo studies demonstrated that, compared with the rhBMP-2 upon CPC and CPC-PDA, the rhBMP-2 upon CPC-PDA-CS exhibited sustained release and induced high quality and more ectopic bone formation. Collectively, these results suggest that rhBMP-2 can be localized within CS-functionalized CPC scaffolds and exert continuous, long-term, and effective osteogenic stimulation. Thus, this work could provide new avenues in mimicking bone extracellular matrix microenvironment and localizing growth factor activity for enhanced bone regeneration. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.