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载有抗 TNF-α单克隆抗体-树枝状聚合物纳米粒的漆树堿改性结冷胶水凝胶在软骨芯片模型中对炎症的调控作用。

Modulation of inflammation by anti-TNF α mAb-dendrimer nanoparticles loaded in tyramine-modified gellan gum hydrogels in a cartilage-on-a-chip model.

机构信息

3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics of University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal.

出版信息

J Mater Chem B. 2021 May 26;9(20):4211-4218. doi: 10.1039/d1tb00802a.

DOI:10.1039/d1tb00802a
PMID:33998627
Abstract

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease characterized by joint inflammation. Since the inflammatory condition plays an important role in the disease process, it is important to develop and test new therapeutic approaches that specifically target and treat joint inflammation. In this study, a human 3D inflammatory cartilage-on-a-chip model was established to test the therapeutic efficacy of anti-TNFα mAb-CS/PAMAM dendrimer NPs loaded-Tyramine-Gellan Gum in the treatment of inflammation. The results showed that the proposed therapeutic approach applied to the human monocyte cell line (THP-1) and human chondrogenic primary cells (hCH) cell-based inflammation system revealed an anti-inflammatory capacity that increased over 14 days. It was also possible to observe that Coll type II was highly expressed by inflamed hCH upon the culture with anti-TNF α mAb-CS/PAMAM dendrimer NPs, indicating that the hCH cells were able maintain their biological function. The developed preclinical model allowed us to provide more robust data on the potential therapeutic effect of anti-TNF α mAb-CS/PAMAM dendrimer NPs loaded-Ty-GG hydrogel in a physiologically relevant model.

摘要

类风湿关节炎(RA)是一种自身免疫性和慢性炎症性疾病,其特征是关节炎症。由于炎症状态在疾病过程中起着重要作用,因此开发和测试专门针对关节炎症的新治疗方法非常重要。在这项研究中,建立了一个人类 3D 炎症性软骨芯片模型,以测试负载有肿瘤坏死因子-α单克隆抗体-CS/PAMAM 树枝状聚合物纳米粒的酪胺-凝胶糖水凝胶在治疗炎症中的治疗效果。结果表明,该治疗方法应用于人单核细胞系(THP-1)和人软骨原代细胞(hCH)基于细胞的炎症系统,显示出超过 14 天的抗炎能力。还可以观察到,在与抗 TNFα mAb-CS/PAMAM 树枝状聚合物纳米粒孵育时,Coll Ⅱ型在炎症 hCH 中高度表达,表明 hCH 细胞能够维持其生物学功能。所开发的临床前模型使我们能够在生理相关模型中提供更有力的证据,证明负载有肿瘤坏死因子-α单克隆抗体-CS/PAMAM 树枝状聚合物纳米粒的酪胺-凝胶糖水凝胶的潜在治疗效果。

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