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Creating a 3D microenvironment for monocyte cultivation: ECM-mimicking hydrogels based on gelatine and hyaluronic acid derivatives

机译:用于单核细胞栽培的3D微环境:基于明胶和透明质酸衍生物的ECM模拟水凝胶

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摘要

Macrophages play a critical role in the initial response to foreign materials in the body. As most biomaterial-based implantable devices would be treated as a foreign body by the immune system, there is a need for systems that can establish a favourable interaction between the implanted biomaterial and the host. Herein, we describe such a system that can be used as an ECM-like microenvironment for macrophage polarization. The hydrogel system was designed to provide a co-crosslinkable microenvironment containing both protein and glycosaminoglycan components, a hydroxyphenyl derivative of gelatine (GTN-HPA) and tyraminated hyaluronic acid (HA-TA). Both polymers can undergo a crosslinking reaction between polymer chains via the same polymerisation initiation system where the polymer network is formed by crosslinks between phenols in GTN-HPA and HA-TA. The mechanical properties and swelling of the hydrogel can be easily controlled as a function of the crosslinking mode and by the ratio of GTN-HPA and HA-TA compounds used. THP-1 monocytes were successfully encapsulated in the gels and cultured for up to 28 days. Cells exhibited higher metabolic activity when encapsulated in softer hydrogels (E approximate to 10 kPa) compared to stiffer (E approximate to 20 kPa) material in which monocytes tended to form large clusters. Encapsulation of monocytes in the material with HA-TA content enhanced the expression of macrophage-related genes. We demonstrated a co-crosslinkable GTN-HPA and HA-TA matrix microenvironment that is suitable for in vitro micro tissue model applications.
机译:巨噬细胞在对身体中的外国材料的初始反应中发挥着关键作用。由于大多数基于生物材料的可植入装置被免疫系统被视为异物,需要一种可以在植入的生物材料和主体之间建立有利相互作用的系统。在此,我们描述了这种可以用作巨噬细胞极化的ECM样显微环境的系统。水凝胶系统被设计为提供含有蛋白质和糖胺聚糖组分的共交联的微环境,明胶(GTN-HPA)的羟基苯基衍生物和酪蛋白透明质酸(HA-TA)。两种聚合物可以通过相同的聚合起始系统在聚合物链之间进行交联反应,其中聚合物网络通过GTN-HPA和HA-TA之间的交联形成。水凝胶的机械性能和溶胀可以容易地作为交联模式的函数和使用的GTN-HPA和HA-TA化合物的函数控制。将THP-1单核细胞成功包封在凝胶中并培养长达28天。与冷却(e大约为20kPa)材料相比,当单核细胞倾向于形成大簇时,细胞当封装在更软的水凝胶(e近似至10kPa)中封装较高的代谢活性。用HA-TA含量封装在材料中的单核细胞增强了巨噬细胞相关基因的表达。我们证明了一种共同可交联的GTN-HPA和HA-TA基质微环境,适用于体外微组织模型应用。

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  • 来源
    《RSC Advances》 |2018年第14期|共9页
  • 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;

    Protip Med 8 Pl Hop F-67000 Strasbourg France;

    Contipro AS Dolni Dobrouc 401 Dolni Dobrouc 56102 Czech Republic;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
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