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The effect of healing phenotype-inducing cytokine formulations within soft hydrogels on encapsulated monocytes and incoming immune cells

机译：愈合表型诱导细胞因子制剂在软水凝胶中对包封的单核细胞和进入免疫细胞的影响

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摘要

The adverse immune responses to implantable biomedical devices is a general problem with important consequences for the functionality of implants. Immunomodulatory soft hydrogel-based interfaces between the implant and the host can attenuate these reactions. Moreover, encapsulation of the patient's own immune cells into these interfaces can lead to the personalisation of implants from the immune reaction point of view. Herein, we described a co-crosslinkable composite hydrogel (composed of gelatin and hyaluronic acid), which could be used for the encapsulation of macrophages in the presence of an anti-inflammatory phenotype-fixing cytokine cocktail. To mimick the incoming immune cells on the coating surface in vivo, peripheral blood mononuclear cells were seeded on the hydrogels. The encapsulation of monocytic cells into the composite hydrogels in the presence of cytokine cocktails at 5x or 10x concentrations led to the spreading of the encapsulated cells instead of the formation of clusters. Moreover, the secretion of the anti-inflammatory cytokines IL-1RA and CCL-18 was significantly increased. The attachment of PBMC to the surface of the hydrogel is dependent on the hydrogel composition and also significantly increased in the presence of the cytokine cocktail together with the number of CD68+ cells on the hydrogel surface. Our study demonstrates that the delivery of a polarisation cocktail with biocompatible hydrogels can control the initial response by the incoming immune cells. This effect can be improved by the encapsulation of autologous monocytes that are also polarised by the cytokine cocktail and secrete additional anti-inflammatory cytokines. This interface can fine tune the initial immune response to an implanted biomaterial in a personalised manner.
机译：对可植入生物医学装置的不利免疫应答是一种普遍的问题，具有植入物功能的重要影响。植入物和宿主之间的免疫调节软水凝胶基界面可以衰减这些反应。此外，患者自己的免疫细胞封装到这些界面中可以导致植入物的个性化免受免疫反应的观点。在此，我们描述了共同可交联的复合水凝胶（由明胶和透明质酸组成），其可用于在抗炎表型固定细胞因子鸡尾酒存在下封装巨噬细胞。为了模仿体内涂层表面上的入射免疫细胞，将外周血单核细胞接种在水凝胶上。在5倍或10倍浓度下在细胞因子鸡尾酒存在下将单核细胞的包封在复合水凝块中导致包封细胞的扩散而不是形成簇。此外，抗炎细胞因子IL-1RA和CCL-18的分泌显着增加。 PBMC对水凝胶表面的附着取决于水凝胶组合物，并且在细胞因子鸡尾酒的存在下也显着增加了水凝胶表面上的CD68 +细胞的数量。我们的研究表明，具有生物相容性水凝胶的偏振鸡尾酒的递送可以通过进入的免疫细胞控制初始反应。通过通过细胞因子鸡尾酒偏振的自体单核细胞的包封可以改善这种效果，并分泌额外的抗炎细胞因子。该界面可以以个性化方式微调对植入生物材料的初始免疫应答。

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  • 来源
    《RSC Advances》 |2019年第37期|共9页
  • 作者

    Scigalkova Ivana; Bystronova Julie; Kovarova Lenka; Pravda Martin; Velebny Vladimir; Riabov Vladimir; Klueter Harald; Kzhyshkowska Julia; Vrana Nihal Engin;

  • 作者单位

    Contipro AS Dolni Dobrouc 401 Dolni Dobrouc 56102 Czech Republic;

    Contipro AS Dolni Dobrouc 401 Dolni Dobrouc 56102 Czech Republic;

    Contipro AS Dolni Dobrouc 401 Dolni Dobrouc 56102 Czech Republic;

    Contipro AS Dolni Dobrouc 401 Dolni Dobrouc 56102 Czech Republic;

    Contipro AS Dolni Dobrouc 401 Dolni Dobrouc 56102 Czech Republic;

    Heidelberg Univ Inst Transfus Med &

    Immunol Med Fac Mannheim Theodor Kutzer Ufer 1-3 D-68167 Mannheim Germany;

    Heidelberg Univ Inst Transfus Med &

    Immunol Med Fac Mannheim Theodor Kutzer Ufer 1-3 D-68167 Mannheim Germany;

    Heidelberg Univ Inst Transfus Med &

    Immunol Med Fac Mannheim Theodor Kutzer Ufer 1-3 D-68167 Mannheim Germany;

    Protip Med 8 Pl Hop F-67000 Strasbourg France;

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