Biomaterials: Silicone implants combined with immunomodulatory hydrogels to control the innate immune response

The latest developments in 3D printed silicone (PDMS: polydimethylsiloxane) implants provide prospects for personalized implants with highly precise anatomical consistency. However, there are still potential adverse reactions, such as granulomas due to immune response. One potential solution to this problem is to use an immunomodulatory coating to control the implant/host interface. Here, A. Dupret-Bories of the Cancer Institute of the University of Toulouse in France, J. Barthes of the French National Institute of Health and Medical Research, and others have designed a new cytokine mixture composed of interleukin-10 and prostaglandin-E2. Macrophages are immobilized in the M2 pro-healing phenotype for a long time to reduce adverse immune responses and promote tissue integration.

Key points of this article:

1) In vitro, the cytokine mixture maintains low levels of pro-inflammatory cytokine (TNF-α and IL-6) secretion, and induces the secretion of IL-10 and the multifunctional scavenging and classification receptor Staabilin- expressed by M2 macrophages. The increase of 1. Then, this mixture is loaded into gelatin hydrogel to develop immunomodulatory materials that can be used as coatings for medical devices.

2) The efficacy of this coating is demonstrated in an in vivo rat model of reconstruction of tracheal defects with 3D printed silicone implants. The coating is stable on the silicone implant for more than 2 weeks, and the controlled release of the components of the mixture reaches at least 14 days. In the body, only 33% of animals with naked silicone implants survived, while 100% of animals survived with immunomodulatory hydrogel implants.

3) The presence of the hydrogel and cytokine mixture reduces the thickness of the inflammatory tissue, the intensity of acute and chronic inflammation, the overall fibroblast response, the presence of edema and the formation of fibrin-like substances (by histological evaluation), and leads to A 100% survival rate.

4) At the systemic level, the presence of immunomodulatory hydrogel significantly reduced the levels of pro-inflammatory cytokines, such as TNF-α, IFN-γ, CXCL1 and MCP-1 on day 7, and markedly on day 21 Reduce IL-1α, IL-1β, CXCL1 and MCP-1 levels. Once applied to 3D printed silicone implants, this new immunomodulatory hydrogel has the ability to control the level of inflammation.

In summary, such thin coatings can be applied to any implant or scaffold used in tissue engineering to reduce the initial immune response, improve the integration and function of these materials, and reduce potential complications related to their existence.

references:

J. Barthes, et al. Biofunctionalization of 3D-printed silicone implants with immunomodulatory hydrogels for controlling the innate immune response: an in vivo model of tracheal defect repair. Biomaterials, 2020.

DOI: https://doi.org/10.1016/j.biomaterials.2020.120549

https://doi.org/10.1016/j.biomaterials.2020.120549

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