The effect of surface modification of mesoporous silica micro-rod scaffold on immune cell activation and infiltration.

The effect of surface modification of mesoporous silica micro-rod scaffold on immune cell activation and infiltration.
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DOI:
10.1016/j.biomaterials.2016.01.026
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发表时间:
2016-03
期刊:
影响因子:
14
通讯作者:
Mooney DJ
Mooney DJ
中科院分区:
工程技术1区
文献类型:
--
作者:
Li WA;Lu BY;Gu L;Choi Y;Kim J;Mooney DJ

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基于生物材料支架的疫苗在产生有效的抗原特异性免疫方面显示出显著的潜力。然而,支架表面化学在引发和调节免疫应答中的作用还没有很好地理解。在本研究中,介孔二氧化硅微棒(MSR)支架修饰与PEG,PEG-RGD和PEG-RDG基团。PEG修饰显著增强了BMDC激活标记物的上调和体外IL-1β的产生,以及体内天然免疫细胞的浸润。与PEG MSR相比,PEG-RGD MSR和PEG-RDG MSR显示出炎症减少,并且效果不是RGD特异性的。最后,发现Nlrp 3炎性体是MSR刺激体外IL-1β产生所必需的,并在调节体内免疫细胞浸润方面发挥关键作用。这些发现表明,简单地调节支架的表面化学可以调节其免疫细胞浸润特征,并对基于新材料的疫苗的设计和开发具有影响。
Biomaterial scaffold based vaccines show significant potential in generating potent antigen-specific immunity. However, the role of the scaffold surface chemistry in initiating and modulating the immune response is not well understood. In this study, a mesoporous silica micro-rod (MSR) scaffold was modified with PEG, PEG-RGD and PEG-RDG groups. PEG modification significantly enhanced BMDC activation marker up-regulation and IL-1β production in vitro, and innate immune cell infiltration in vivo. PEG-RGD MSRs and PEG-RDG MSRs displayed decreased inflammation compared to PEG MSRs, and the effect was not RGD specific. Finally, the Nlrp3 inflammasome was found to be necessary for MSR stimulated IL-1β production in vitro and played a key role in regulating immune cell infiltration in vivo. These findings suggest that simply modulating the surface chemistry of a scaffold can regulate its immune cell infiltration profile and have implications for the design and development of new material based vaccines.