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体外和体内仿生 PLGA-(PEG-ASP)n 共聚物负载新型合成 BMP-2 相关肽诱导骨生成。

Bone induction by biomimetic PLGA-(PEG-ASP)n copolymer loaded with a novel synthetic BMP-2-related peptide in vitro and in vivo.

机构信息

Department of Orthopedics, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

出版信息

J Control Release. 2010 Jun 1;144(2):190-5. doi: 10.1016/j.jconrel.2010.02.016. Epub 2010 Feb 22.

Abstract

BMP-2 is one of the most important growth factors of bone regeneration. Polylactide-co-glycolic acid (PLGA), which is used as a biodegradable scaffold for delivering therapeutic agents, has been intensively investigated. In previous studies, we synthesized a novel BMP-2-related peptide (designated P24) and found that it could enhance the osteoblastic differentiation of bone marrow stromal cells (BMSCs). The objective of this study was to construct a biomimetic composite by incorporating P24 into a modified PLGA-(PEG-ASP)n copolymer to promote bone formation. In vitro, our results demonstrated that PLGA-(PEG-ASP)n scaffolds were shown to be an efficient system for sustained release of P24. Significantly more BMSCs attached to the P24/PLGA-(PEG-ASP)n and PLGA-(PEG-ASP)n membranes than to PLGA, and the cells in the two groups subsequently proliferated more vigorously than those in the PLGA group. The expression of osteogenic markers in P24/PLGA-(PEG-ASP)n group was stronger than that in the PLGA-(PEG-ASP)n and PLGA groups. Radiographic and histological examination, Western blotting and RT-PCR showed that P24/PLGA-(PEG-ASP)n scaffold could induce more effective ectopic bone formation in vivo, as compared with PLGA-(PEG-ASP)n or gelatin sponge alone. It is concluded that the PLGA-(PEG-ASP)n copolymer is a good P24 carrier and can serve as a good scaffold for controlled release of P24. This novel P24/PLGA-(PEG-ASP)n composite promises to be an excellent biomaterial for inducing bone regeneration.

摘要

骨形态发生蛋白 2 是骨再生最重要的生长因子之一。聚乳酸-共-羟基乙酸(PLGA)被用作递药的可生物降解支架,已被广泛研究。在以前的研究中,我们合成了一种新型的骨形态发生蛋白 2 相关肽(命名为 P24),并发现它可以增强骨髓基质细胞(BMSCs)的成骨分化。本研究的目的是通过将 P24 掺入修饰的 PLGA-(PEG-ASP)n 共聚物中来构建仿生复合材料,以促进骨形成。体外实验结果表明,PLGA-(PEG-ASP)n 支架是 P24 持续释放的有效体系。与 PLGA 相比,更多的 BMSCs 附着在 P24/PLGA-(PEG-ASP)n 和 PLGA-(PEG-ASP)n 膜上,并且这两组细胞的增殖速度明显快于 PLGA 组。P24/PLGA-(PEG-ASP)n 组中成骨标志物的表达强于 PLGA-(PEG-ASP)n 和 PLGA 组。影像学和组织学检查、Western blot 和 RT-PCR 表明,与单独使用 PLGA-(PEG-ASP)n 或明胶海绵相比,P24/PLGA-(PEG-ASP)n 支架可以在体内诱导更有效的异位骨形成。综上所述,PLGA-(PEG-ASP)n 共聚物是 P24 的良好载体,可作为 P24 控释的良好支架。这种新型 P24/PLGA-(PEG-ASP)n 复合材料有望成为一种诱导骨再生的优良生物材料。

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