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Host responses to implants revealed by intravital microscopy

Abstract

Biomaterials, biomedical devices and engineered cell grafts can be implanted to restitute tissue anatomy and function. Such implants can either integrate physiologically, with no or minimal scarring, or induce chronic inflammation and the foreign body response, which leads to graft failure. Intravital microscopy in small animal models can be applied to visualize the structure and integration of implanted natural and synthetic fibres, metals, cells within hydrogel carriers and engineered tissues, as well as the stepwise cellular and molecular tissue response. In this Review, we discuss how intravital microscopy can reveal regenerative and pathological responses to implants, including wound healing and graft integration, which depend on the time-controlled activation of macrophages and early neovascularization, and adverse reactions, such as the foreign body response and fibrosis. The combination of improved materials designs, detection of cell signalling using molecular reporters and targeted intervention will allow the development of strategies to improve graft integration and functionality.

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Fig. 1: Fluorescence and nonlinear microscopy to detect implant materials and molecular signalling in cells.
Fig. 2: Animal models for intravital microscopy of implant biology.
Fig. 3: Tissue-specific implant integration.
Fig. 4: Foreign body response.

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Acknowledgements

The authors thank J. Conway and P. Timpson for helpful discussions. This work was supported by the MD Anderson Cancer Center Prostate Cancer SPORE (P50 CA140388-09) and Bayer HealthCare Pharmaceuticals (57440) to E.D. and the NWO-VICI (918.11.626), the European Research Council (617430-DEEPINSIGHT), the NWO Gravity Program Institute for Chemical Immunology and the Cancer Genomics Center, the Netherlands to P.F. The Genitourinary Cancers Program of the Cancer Center Support Grant (CCSG) shared resources at MD Anderson Cancer Center is supported by NIH/NCI award number P30 CA016672.

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Dondossola, E., Friedl, P. Host responses to implants revealed by intravital microscopy. Nat Rev Mater (2021). https://doi.org/10.1038/s41578-021-00369-x

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