PNIPAM hydrogel induces skeletal muscle inflammation response

PNIPAM hydrogel induces skeletal muscle inflammation response
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PNIPAM 水凝胶诱导骨骼肌炎症反应

DOI:
10.1039/c5ra01679g
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发表时间:
2015-03
期刊:
影响因子:
3.9
通讯作者:
Liao Hua
Liao Hua
中科院分区:
化学3区
文献类型:
--
作者:
Zhu Rong;Wu Gang;Liu Xinghui;Shi DanDan;Cao Biao;Gu Ruicai;Xiao Jiangwei;Liao Hua

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尽管研究人员认为水凝胶在体内外都具有良好的生物相容性,但这类合成聚合物在体内仍具有不同的免疫原性行为,并产生持久的炎症反应。在这项研究中,我们试图探讨肌肉植入一个特定的PNIPAM水凝胶,以诱导小鼠慢性炎症-肌肉损伤模型的可能性。我们将一种温度敏感的PNIPAM水凝胶与或不与快速型骨骼肌C蛋白混合,注射到WT B6小鼠的胫骨前肌(TA)中,并分析注射后15、30和60天TA肌肉中的单核细胞浸润、肌肉自身抗原和TLR表达、以及肌内CD 8 + T细胞浸润和新生肌纤维表面MHC-I表达。我们发现PNIPAM水凝胶在2个月内诱导骨骼肌炎症。水凝胶注射区的炎症反应在第30天达到高峰,然后逐渐降低。有趣的是,PNIPAM水凝胶/C蛋白的混合物比单独的水凝胶或C蛋白注射引发更严重和持续的肌肉炎症反应。免疫荧光分析表明,水凝胶诱导慢性肌肉炎症,其特征在于CD 8 + T细胞浸润和I类MHC阳性再生肌纤维增加。我们的工作为使用水凝胶作为生物驱动器制备肌肉炎症的动物模型带来了新的希望。水凝胶诱导的肌肉损伤模型可用于研究肌肉损伤、炎症和再生的病理机制。
Although researchers believe hydrogels have favorable biocompatibility in vitro and in vivo, these kinds of synthetic polymers still have different immunogenic behavior in vivo, and bring forth a long-lasting inflammatory response. In this study, we attempt to explore the possibility of intramuscular implantation of a specific PNIPAM hydrogel to induce a chronic inflammatory-myoinjury model in mice. We injected a temperature-sensitive PNIPAM hydrogel mixed with or without fast-type skeletal muscle C protein, into the tibialis anterior muscle (TA) of WT B6 mice, and analyzed mononuclear cell infiltration, muscle autoantigens and TLRs expression, and the intramuscular CD8+ T cells infiltration and MHC-I expression on the surface of the new myofiber in TA muscle on day 15, 30 and 60 post-injection. We found that the PNIPAM hydrogel induces a skeletal muscle inflammation over 2 months. The inflammation response in the hydrogel injection area reached the peak on day 30, and then gradually decreased. Interestingly, the mixture of PNIPAM hydrogel/C protein initiated a more severe and persistent muscle inflammatory response, than hydrogel, or C protein injection alone. Immunofluorescence analysis demonstrated that the hydrogel induced chronic muscle inflammation featured by the CD8+ T cell infiltration and increased class I MHC-positive regenerating myofibers. Our work holds new promise for preparing an animal model of muscle inflammation using hydrogel as a bio-driver. The hydrogel induced-myoinjury model may be useful for investigating pathologic mechanisms of muscle injury, inflammation and regeneration.
DOI: 10.1002/art.27465
发表时间: 2010-07-01
影响因子: --
作者:
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DOI: 10.1096/fj.10-174755
发表时间: 2011-07
期刊: The FASEB Journal
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发表时间: 1987-03
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DOI: 10.1016/j.biomaterials.2010.02.026
发表时间: 2010-06-01
期刊: BIOMATERIALS
影响因子: 14
作者:
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DOI: 10.1097/01.prs.0000221007.97115.1d
发表时间: 2006-10-01
影响因子: 3.6
作者:
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