Ščigalková Ivana, Bystroňová Julie, Kovářová Lenka, Pravda Martin, Velebný Vladimír, Riabov Vladimir, Klüter Harald, Kzhyshkowska Julia, Vrana Nihal Engin
Contipro a.s. Dolni Dobrouc 401 561 02 Dolni Dobrouc Czech Republic.
Institute of Physical Chemistry, Faculty of Chemistry, Brno University of Technology Purkynova 464/118 612 00 Brno Czech Republic.
RSC Adv. 2019 Jul 10;9(37):21396-21404. doi: 10.1039/c9ra02878a. eCollection 2019 Jul 5.
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 , 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 5× or 10× 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.
对可植入生物医学设备的不良免疫反应是一个普遍问题，对植入物的功能有重要影响。植入物与宿主之间基于免疫调节软水凝胶的界面可以减弱这些反应。此外，将患者自身的免疫细胞封装到这些界面中可以从免疫反应的角度实现植入物的个性化。在此，我们描述了一种可共交联的复合水凝胶（由明胶和透明质酸组成），其可用于在存在抗炎表型固定细胞因子鸡尾酒的情况下封装巨噬细胞。为了模拟涂层表面传入的免疫细胞，将外周血单核细胞接种到水凝胶上。在5倍或10倍浓度的细胞因子鸡尾酒存在下，将单核细胞封装到复合水凝胶中导致封装细胞的扩散而不是形成簇。此外，抗炎细胞因子IL-1RA和CCL-18的分泌显著增加。PBMC与水凝胶表面的附着取决于水凝胶的组成，并且在细胞因子鸡尾酒存在下以及水凝胶表面CD68+细胞数量也显著增加。我们的研究表明，用生物相容性水凝胶递送极化鸡尾酒可以控制传入免疫细胞的初始反应。通过封装也被细胞因子鸡尾酒极化并分泌额外抗炎细胞因子的自体单核细胞，可以改善这种效果。这种界面可以以个性化的方式微调对植入生物材料的初始免疫反应。
