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首页> 外文期刊>Biomaterials Science >Modulating inflammation in a cutaneous chronic wound model by IL-10 released from collagen-silica nanocomposites via gene delivery
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Modulating inflammation in a cutaneous chronic wound model by IL-10 released from collagen-silica nanocomposites via gene delivery

机译：通过基因递送从胶原二氧化硅纳米复合材料释放的IL-10在皮肤慢性伤口模型中调节炎症

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摘要

Cutaneous chronic wounds remain a major clinical challenge which requires the development of novel wound dressings. Previously, we showed that collagen-silica nanocomposites consisting of polyethyl-eneimine (PEI)-DNA complexes associated with silica nanoparticles (SiNP), collagen hydrogel and 3T3 fibroblasts, can work as a local "cell factory". Indeed, the "in-gel" transfection leads to a sustained production and release of biomolecules. Herein, we further explored the possibility for nanocomposites to deliver interleukin-10 (IL-10), a potent anti-inflammatory cytokine, which favors tissue repair. Its anti-inflammatory effect was evaluated in an in vitro inflammation model carried out by LPS (lipopolysaccharide) activation of macrophages embedded in collagen gel. The IL-10 synthesis from nanocomposites was detected over one week in the range of 200-400 pg mL(-1) and reached a maximum at day 5 without any observed cytotoxic effects. PEI10-SiNP outperformed free PEI10 and PEI25-SiNP, implying that the introduction of SiNP improved the transfection efficiency of low Mw of PEI. In addition, the structure and mechanical properties of collagen-silica nanocomposites were stable over one week. Subsequently, the ability of nanocomposites to modulate inflammation was tested in a 3D model of inflammation. The decrease of TNF-alpha and IL-1 beta gene expression by 20-80% indicated successful inhibition of inflammation by IL-10 released from nanocomposites. Taken together, the nanocomposites are capable of producing effective doses of IL-10 which inhibit the synthesis of pro-inflammatory cytokines and favor the expression of wound healing cytokines. Therefore, the as-constructed 3D gene delivery system represents a promising strategy for the controlled release of therapeutic biomolecules favoring cutaneous wound healing.
机译：皮肤慢性伤口仍然是需要开发新型伤口敷料的主要临床挑战。以前，我们表明，由二氧化硅纳米粒子（SINP），胶原水凝胶和3T3成纤维细胞相关的聚乙基 - 烯氨基（PEI）-DNA复合物组成的胶原二氧化硅纳米复合材料可以作为当地的“细胞厂”。实际上，“凝胶”转染导致生物分子的持续生产和释放。在此，我们进一步探讨了纳米复合材料的可能性，以提供白细胞介素-10（IL-10），一种有效的抗炎细胞因子，其利用组织修复。在胶原凝胶中嵌入胶原凝胶的LPS（脂多糖）活化的体外炎症模型中评估其抗炎作用。在200-400pg ml（-1）的范围内检测来自纳米复合材料的IL-10合成，并在第5天没有任何观察到的细胞毒性效应达到最大值。 PEI10-SINP优于免费的PEI10和PEI25-SINP，这意味着SINP的引入改善了PEI低MW的转染效率。此外，胶原二氧化硅纳米复合材料的结构和机械性能在一周内稳定。随后，在炎症的3D模型中测试纳米复合材料以调节炎症的能力。 TNF-α和IL-1β基因表达的降低20-80％表明通过从纳米复合材料释放的IL-10成功抑制炎症。纳入纳米复合材料能够产生有效剂量的IL-10，其抑制促炎细胞因子的合成，并有利于伤口愈合细胞因子的表达。因此，AS构建的3D基因递送系统代表了有利于皮肤伤口愈合的治疗生物分子的控释释放的有希望的策略。

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  • 来源
    《Biomaterials Science》 |2018年第2期|共9页
  • 作者

    Wang Xiaolin; Coradin Thibaud; Helary Christophe;

  • 作者单位

    UPMC Univ Paris 06 Sorbonne Univ CNRS Lab Chim Matiere Condensee Paris UMR 7574 F-75005 Paris France;

    UPMC Univ Paris 06 Sorbonne Univ CNRS Lab Chim Matiere Condensee Paris UMR 7574 F-75005 Paris France;

    UPMC Univ Paris 06 Sorbonne Univ CNRS Lab Chim Matiere Condensee Paris UMR 7574 F-75005 Paris France;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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