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干细胞骨刺激支架:BMP-7 衍生肽修饰的藻酸盐多孔支架促进人间充质干细胞的聚集和骨向分化。

Osteostimulation scaffolds of stem cells: BMP-7-derived peptide-decorated alginate porous scaffolds promote the aggregation and osteo-differentiation of human mesenchymal stem cells.

机构信息

Department of Stomatology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.

Laboratory for Biomaterials and Regenerative Medicine, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.

出版信息

Biopolymers. 2018 Jul;109(7):e23223. doi: 10.1002/bip.23223. Epub 2018 May 6.

Abstract

The scaffolds for stem cell-based bone tissue engineering should hold the ability to guide stem cells osteo-differentiating. Otherwise, stem cells will differentiate into unwanted cell types or will form tumors in vivo. Alginate, a natural polysaccharide with great biocompatibility, was widely used in biomedical applications. However, the limited bioactivity and poor osteogenesis capability of pristine alginate hampered its further application in tissue engineering. In this work, a bone forming peptide-1 (BFP-1), derived from bone morphogenetic protein-7, was grafted to alginate polymer chains to prepare peptide-decorated alginate porous scaffolds (pep-APS) for promoting osteo-differentiation of human mesenchymal stem cells (hMSCs). SEM images of pep-APS exhibited porous structure with about 90% porosity (pore size 100-300 μm), which was appropriate for hMSCs ingrowth. The adhesion, proliferation and aggregation of hMSCs grown on pep-APS were enhanced in vitro. Moreover, pep-APS promoted the alkaline phosphatase (ALP) activity of hMSCs, and the osteo-related genes expression was obviously up-regulated. The immunochemical staining and western blot analysis results showed high expression level of OCN and Col1a1 in the hMSCs grown on pep-APS. This work provided a facile and valid strategy to endow the alginate polymers themselves with specific bioactivity and prepare osteopromoting scaffold with enhanced osteogenesis ability, possessing potential applications in stem cell therapy and regenerative medicine.

摘要

用于干细胞骨组织工程的支架应具有引导干细胞成骨分化的能力。否则,干细胞将分化为不需要的细胞类型,或者在体内形成肿瘤。藻酸盐是一种具有良好生物相容性的天然多糖,已广泛应用于生物医学领域。然而,原始藻酸盐的生物活性有限和成骨能力差,限制了其在组织工程中的进一步应用。在这项工作中,一种来源于骨形态发生蛋白-7 的成骨肽-1 (BFP-1) 被接枝到藻酸盐聚合物链上,以制备肽修饰的藻酸盐多孔支架 (pep-APS),用于促进人间充质干细胞 (hMSCs) 的成骨分化。pep-APS 的 SEM 图像显示出具有约 90%孔隙率 (孔径 100-300μm) 的多孔结构,适合 hMSCs 长入。体外实验表明,pep-APS 增强了 hMSCs 的黏附、增殖和聚集。此外,pep-APS 还促进了 hMSCs 的碱性磷酸酶 (ALP) 活性,明显上调了成骨相关基因的表达。免疫化学染色和 Western blot 分析结果表明,在 pep-APS 上生长的 hMSCs 中 OCN 和 Col1a1 的表达水平较高。这项工作为赋予藻酸盐聚合物本身特定的生物活性提供了一种简单有效的策略,并制备了具有增强成骨能力的促骨支架,在干细胞治疗和再生医学中具有潜在的应用前景。

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