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从小肠黏膜下层/聚乳酸支架材料持续递送PlGF-2融合的BMP2相关肽P28用于骨组织再生。

Sustained delivery of PlGF-2-fused BMP2-related peptide P28 from small intestinal submucosa/polylactic acid scaffold material for bone tissue regeneration.

作者信息

Xiong Zekang, Cui Wei, Sun Tingfang, Teng Yu, Qu Yanzhen, Yang Liang, Zhou Jinge, Chen Kaifang, Yao Sheng, Shao Zengwu, Guo Xiaodong

机构信息

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology 1277 Jiefang Avenue Wuhan 430022 People's Republic of China

Department of Orthopedics, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430000 People's Republic of China.

出版信息

RSC Adv. 2020 Feb 19;10(12):7289-7300. doi: 10.1039/c9ra07868a. eCollection 2020 Feb 13.

Abstract

Bone morphogenetic protein 2 (BMP-2) is one of the most important factors for bone tissue formation. However, its use over the past decade has been associated with numerous side effects. This is due to the fact that recombinant human (rh) BMP-2 has several biological functions, as well as that non-physiological high dosages were commonly administered. In this study, we synthesized a novel BMP-2-related peptide (designated P28) and fused a mutant domain in placenta growth factor-2 (PlGF-2) that allowed for the "super-affinity" of extracellular matrix proteins to P28, effectively controlling the release of low dosage P28 from small intestinal submucosa/polylactic acid (SIS/PLA) scaffolds. These have been shown to be excellent scaffold materials both and . The aim of this study was to determine whether these scaffolds could support the controlled release of P28 over time, and whether the composite materials could serve as structurally and functionally superior bone substitutes . Our results demonstrated that P28 could be released slowly from SIS/PLA to promote the adhesion, proliferation, and differentiation of bone marrow stromal cells (BMSCs) . , radiographic and histological examination showed that SIS/PLA/P28/PlGF-2 completely repaired critical-size bone defects, compared to SIS/PLA, SIS/PLA/PlGF-2, or SIS/PLA/P28 alone. These findings suggest that this controlled release system may have promising clinical applications in bone tissue engineering.

摘要

骨形态发生蛋白2(BMP - 2)是骨组织形成的最重要因素之一。然而,在过去十年中其使用伴随着众多副作用。这是因为重组人(rh)BMP - 2具有多种生物学功能,并且通常给予非生理性的高剂量。在本研究中,我们合成了一种新型的BMP - 2相关肽(命名为P28),并在胎盘生长因子 - 2(PlGF - 2)中融合了一个突变结构域,该结构域使细胞外基质蛋白对P28具有“超亲和力”,从而有效控制低剂量P28从小肠黏膜下层/聚乳酸(SIS/PLA)支架中的释放。这些已被证明是优良的支架材料。本研究的目的是确定这些支架是否能随时间支持P28的控释,以及复合材料是否可作为结构和功能上更优越的骨替代物。我们的结果表明,P28可从SIS/PLA中缓慢释放,以促进骨髓基质细胞(BMSC)的黏附、增殖和分化。此外,影像学和组织学检查显示,与单独的SIS/PLA、SIS/PLA/PlGF - 2或SIS/PLA/P28相比,SIS/PLA/P28/PlGF - 2完全修复了临界尺寸的骨缺损。这些发现表明,这种控释系统在骨组织工程中可能具有广阔的临床应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b04/9049782/973fd25b15aa/c9ra07868a-f1.jpg

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