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MBG 改性 β-TCP 支架通过 FAK/MAPK 信号通路促进间充质干细胞黏附和成骨分化。

MBG-Modified β-TCP Scaffold Promotes Mesenchymal Stem Cells Adhesion and Osteogenic Differentiation via a FAK/MAPK Signaling Pathway.

机构信息

Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200011, People's Republic of China.

出版信息

ACS Appl Mater Interfaces. 2017 Sep 13;9(36):30283-30296. doi: 10.1021/acsami.7b02466. Epub 2017 Aug 28.

DOI:10.1021/acsami.7b02466
PMID:28820575
Abstract

The β-TCP scaffold has been widely used as a bone graft substitute, but the traditional PMMA molding method-induced undesirable mechanical strength and poor interconnectivity still have not been addressed until now. In this study, a MBG-based PU foam templating method was developed to fabricate β-TCP scaffolds with desirable microtopography. The MBG gel, as both binder and modifier, prepared by a modified sol-gel method with controlled viscosity is incorporated with β-TCP powder and thereafter is impregnated into PU foam. The resultant hybrid scaffolds exhibited interconnected macropores (200-500 μm) and distinctive micropores (0.2-1.5 μm), especially for the TCP/25MBG (with 25 wt % content MBG). As expected, the compression strength of β-TCP/MBG composite scaffolds was enhanced with increasing MBG content, and TCP/50MBG (with 50 wt % content MBG) exhibited almost 100-fold enhancement compared to the pure β-TCP. Intriguingly, the cell affinity and osteogenic capacity of rBMSCs were also dramatically improved the best on TCP/25MBG. Further investigation found that the subtle, grainy-like microtopography, not the chemical composition, of the TCP/25MBG favored the adsorption of Fn and expression of integrin α5β1 and further facilitated FA formation and the expression of p-FAK, following activation of the MAPK/ERK signaling pathway and ultimately upregulated expression of osteogenic genes. Further in vivo experiments confirmed the promoted osteogenesis of TCP/25MBG in vivo. The results suggest that such a novel MBG-based PU foam templating method offers new guidance to construct hierarchically porous scaffolds, and the prepared MBG-modified β-TCP scaffold will have great potential for future use in bone tissue regeneration.

摘要

β-TCP 支架已被广泛用作骨移植物替代物,但直到现在,传统的 PMMA 成型方法所导致的不理想的机械强度和较差的连通性仍然没有得到解决。在本研究中,开发了一种基于 MBG 的 PU 泡沫模板法来制备具有理想微观形貌的β-TCP 支架。MBG 凝胶作为结合剂和改性剂,通过具有受控粘度的改进溶胶-凝胶法制备,与β-TCP 粉末混合后再浸渍到 PU 泡沫中。所得的混合支架表现出相互连通的大孔(200-500μm)和独特的微孔(0.2-1.5μm),特别是对于 TCP/25MBG(含有 25wt%MBG)。不出所料,随着 MBG 含量的增加,β-TCP/MBG 复合支架的压缩强度得到提高,并且与纯β-TCP 相比,TCP/50MBG(含有 50wt%MBG)的增强幅度接近 100 倍。有趣的是,rBMSCs 的细胞亲和力和成骨能力在 TCP/25MBG 上也得到了极大的提高。进一步的研究发现,TCP/25MBG 的细微、粒状微观形貌,而不是其化学成分,有利于 Fn 的吸附以及整合素 α5β1 的表达,从而进一步促进 FA 的形成和 p-FAK 的表达,激活 MAPK/ERK 信号通路,并最终上调成骨基因的表达。进一步的体内实验证实了 TCP/25MBG 在体内促进成骨的作用。结果表明,这种新型的基于 MBG 的 PU 泡沫模板法为构建分级多孔支架提供了新的指导,并且制备的 MBG 改性β-TCP 支架在未来的骨组织再生中具有很大的应用潜力。

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