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.

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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 ≈ 10 kPa) compared to stiffer (E ≈ 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.

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• časopisecké články MeSH