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 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.

Contipro a s Dolni Dobrouc 401 561 02 Dolni Dobrouc Czech Republic

Inserm UMR 1121 Biomaterials and Bioengineering 11 rue Humann 67085 Strasbourg France

Institute for Transfusion Medicine and Immunology Medical Faculty Mannheim University of Heidelberg Theodor Kutzer Ufer 1 3 68167 Mannheim Germany

Institute of Physical Chemistry Faculty of Chemistry Brno University of Technology Purkynova 464 118 612 00 Brno Czech Republic

Laboratory for Translational Cellular and Molecular Biomedicine Tomsk State University 36 Lenin Prospekt Tomsk 634050 Russia

Protip Medical 8 Place de l'Hôpital 67000 Strasbourg France

Red Cross Blood Service Baden Württemberg Hessen Friedrich Ebert Str 107 D 68167 Mannheim Germany

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