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骨髓基质细胞在生物活性自组装肽凝胶中的原位软骨形成分化

In situ chondrogenic differentiation of bone marrow stromal cells in bioactive self-assembled peptide gels.

作者信息

Kim Ji Eun, Kim Soo Hyun, Jung Youngmee

机构信息

Biomaterials Research Center, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 136-705, Republic of Korea.

Biomaterials Research Center, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 136-705, Republic of Korea; Department of Biomedical Engineering, University of Science and Technology (UST), Seoul 136-791, Republic of Korea.

出版信息

J Biosci Bioeng. 2015 Jul;120(1):91-8. doi: 10.1016/j.jbiosc.2014.11.012. Epub 2014 Dec 22.

DOI:10.1016/j.jbiosc.2014.11.012
PMID:25540912
Abstract

Articular cartilage is a specific tissue that lacks nerves and blood vessels and has limited self-repair abilities. Accordingly, it is necessary to develop new technology for the regeneration of cartilage to overcome therapeutic limitations. Recently, there have been several studies investigating the use of peptide hydrogel scaffolds, which are biocompatible and have low immunogenicity, for cartilage tissue engineering. In this study, we used self-assembled peptide hydrogels with repeating peptide sequences and bioactive motifs at the end of repeating sequences, which are collagen mimetic peptides (CMPs). CMPs that have a unique collagen-like triple helical conformation have been shown to associate with collagen molecules and fibers via a strand invasion process. In order to confirm the biological activities of the modified bioactive peptide hydrogels, the role of functional motifs in in situ chondrogenic differentiation of rabbit bone marrow stromal cells (rBMSCs) was examined. To compensate for the weaker mechanical properties of peptide hydrogels, we used poly (L-lactide-co-caprolactone) (PLCL) scaffolds, which were loaded with the self-assembled peptides into which the bioactive motifs had been incorporated. Then, we performed in vitro and in vivo analyses with the rBMSC/PLCL-peptide hydrogel complexes. The results indicated that the secretion of a cartilage-specific extracellular matrix and gene expression concerned with chondrogenic differentiation were increased by CMP motifs. In conclusion, it was confirmed that CMP-modified self-assembled peptide hydrogels could effectively enhance chondrogenic differentiation in situ, and, consequently, they could be a good biomaterial for cartilage tissue engineering.

摘要

关节软骨是一种特殊组织,缺乏神经和血管,自我修复能力有限。因此,有必要开发新的软骨再生技术以克服治疗局限性。最近,有几项研究调查了使用具有生物相容性和低免疫原性的肽水凝胶支架用于软骨组织工程。在本研究中,我们使用了具有重复肽序列且在重复序列末端带有生物活性基序的自组装肽水凝胶,这些是胶原模拟肽(CMPs)。已显示具有独特胶原样三螺旋构象的CMPs通过链侵入过程与胶原分子和纤维结合。为了证实修饰的生物活性肽水凝胶的生物学活性,研究了功能基序在兔骨髓基质细胞(rBMSCs)原位软骨形成分化中的作用。为了弥补肽水凝胶较弱的机械性能,我们使用了聚(L-丙交酯-共-己内酯)(PLCL)支架,其负载了已掺入生物活性基序的自组装肽。然后,我们对rBMSC/PLCL-肽水凝胶复合物进行了体外和体内分析。结果表明,CMP基序增加了软骨特异性细胞外基质的分泌以及与软骨形成分化相关的基因表达。总之,证实了CMP修饰的自组装肽水凝胶可有效增强原位软骨形成分化,因此,它们可能是软骨组织工程的良好生物材料。

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