Sustained delivery of PlGF-2(123-144*)-fused BMP2-related peptide P28 from small intestinal submucosa/polylactic acid scaffold material for bone tissue regeneration.

Sustained delivery of PlGF-2(123-144*)-fused BMP2-related peptide P28 from small intestinal submucosa/polylactic acid scaffold material for bone tissue regeneration.
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小肠粘膜下层/聚乳酸​​支架材料持续递送 PlGF-2(123-144) 融合 BMP2 相关肽 P28 用于骨组织再生

DOI:
10.1039/c9ra07868a
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发表时间:
2020-02-13
期刊:
影响因子:
3.9
通讯作者:
Guo, Xiaodong
Guo, Xiaodong
中科院分区:
化学3区
文献类型:
--
作者:
Xiong, Zekang;Cui, Wei;Sun, Tingfang;Teng, Yu;Qu, Yanzhen;Yang, Liang;Zhou, Jinge;Chen, Kaifang;Yao, Sheng;Shao, Zengwu;Guo, Xiaodong

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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,在过去的十年中,它的使用与许多副作用有关。这是由于重组人(rh)BMP-2具有多种生物学功能,以及通常施用非生理高剂量的事实。在这项研究中,我们合成了一种新的BMP-2相关肽(命名为P28),并融合了胎盘生长因子-2(PlGF-2123-144*)的突变结构域,允许细胞外基质蛋白对P28的“超亲和力”,有效地控制了小剂量P28从小肠粘膜下层/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在体内和体外。本研究的目的是确定这些支架是否可以支持P28随时间的控制释放,以及复合材料是否可以在体内作为结构和功能上优越的上级骨替代品。结果表明,P28在SIS/PLA中缓慢释放,促进骨髓基质细胞(BMSCs)的粘附、增殖和分化。在体内,放射学和组织学检查显示,与单独的SIS/PLA、SIS/PLA/PlGF-2123 - 144* 或SIS/PLA/P28相比,SIS/PLA/P28/PlGF-2123 - 144* 完全修复了临界尺寸的骨缺损。这些结果表明,这种控释系统可能在骨组织工程中具有良好的临床应用前景。从SIS/PLA支架持续递送PlGF-2123-144* 融合的BMP 2相关肽P28促进骨髓基质细胞的粘附、增殖和成骨分化。该系统有效地促进节段性骨修复。
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-2123-144*) 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 in vivo and in vitro. 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 in vivo. 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) in vitro. In vivo, radiographic and histological examination showed that SIS/PLA/P28/PlGF-2123-144* completely repaired critical-size bone defects, compared to SIS/PLA, SIS/PLA/PlGF-2123-144*, or SIS/PLA/P28 alone. These findings suggest that this controlled release system may have promising clinical applications in bone tissue engineering. Sustained delivery of PlGF-2123-144*-fused BMP2-related peptide P28 from SIS/PLA scaffold facilitate the adhesion, proliferation, and osteogenic differentiation of bone marrow stromal cells. This system effectively promotes segmental bone repair.
使用可变的长度聚谷氨酸结构域,可调节从羟基磷灰石生物材料和同种异体移植骨中递送生物活性肽。
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发表时间: 2014-04
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发表时间: 2014-02-21
期刊: SCIENCE
影响因子: 56.9
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发表时间: 2002-12-01
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影响因子: 3
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