文章内容（英文）
The recent advances in 3D-printed silicone (PDMS: polydimethylsiloxane) implants present prospects for personalized implants with highly accurate anatomical conformity. However, a potential adverse effect, such as granuloma formation due to immune reactions, still exists. One potential way to overcome this problem is to control the implant/host interface using immunomodulatory coatings. In this study, a new cytokine cocktail composed of interleukin-10 and prostaglandin-E2 was designed to decrease adverse immune reactions and promote tissue integration by fixing macrophages into M2 pro-healing phenotype for an extended period of time. In vitro, the cytokine cocktail maintained low levels of pro-inflammatory cytokine (TNF-α and IL-6) secretions and induced the secretion of IL-10 and the upregulation of multifunctional scavenging and sorting receptor stabilin-1, expressed by M2 macrophages. This cocktail was then loaded in a gelatine-based hydrogel to develop an immunomodulatory material that could be used as a coating for medical devices. The efficacy of this coating was demonstrated in an in vivo rat model during the reconstruction of a tracheal defect by 3D-printed silicone implants. The coating was stable on the silicone implants for over 2 weeks, and the controlled release of the cocktail components was achieved for at least 14 days. In vivo, only 33% of the animals with bare silicone implants survived, whereas 100% of the animals survived with the implant equipped with the immunomodulatory hydrogel. The presence of the hydrogel and the cytokine cocktail diminished the thickness of the inflammatory tissue, the intensity of both acute and chronic inflammation, the overall fibroblastic reaction, the presence of oedema and the formation of fibrinoid (assessed by histology) and led to a 100% survival rate. At the systemic level, the presence of immunomodulatory hydrogels significantly decreased pro-inflammatory cytokines such as TNF-α, IFN-γ, CXCL1 and MCP-1 levels at day 7 and significantly decreased IL-1α, IL-1β, CXCL1 and MCP-1 levels at day 21. The ability of this new immunomodulatory hydrogel to control the level of inflammation once applied to a 3D-printed silicone implant has been demonstrated. Such thin coatings can be applied to any implants or scaffolds used in tissue engineering to diminish the initial immune response, improve the integration and functionality of these materials and decrease potential complications related to their presence.epartment of Biomedical Genetics and Center for Oral Biology, University of Rochester Medical Center, Rochester, NY, USA;Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove, Brisbane, QLD, 4059, Australia;UQ Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, QLD, 4102, Australia;Institute of Medical Biotechnology, Friedrich-Alexander-University Erlangen-Nuremberg, Paul-Gordan-Str.3, 91052, Erlangen, Germany;Australian Research Council (ARC) Training Centre in Additive Biomanufacturing, Queensland University of Technology (QUT), Kelvin Grove, QLD, 4059, Australia;Herston Biofabrication Institute, Metro North Hospital and Health Service, Brisbane, QLD, 4029, Australia;The University of Queensland, School of Dentistry, Herston, Queensland, Australia;niChe Lab for Stem Cell and Regenerative Medicine, Department of Biochemical Science and Technology, National Taiwan University, Taipei 10617, Taiwan;Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan;Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, 10617, Taiwan;Institute of Polymer Science and Engineering, National Taiwan University, Taipei 10617, Taiwan;School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, 030001, China;Peking University-Tsinghua University Center for Life Sciences, Peking University, Beijing, 100871, China;Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China;Beijing Capture Tech Co., Ltd., Beijing, 102413, China;The Radiology Department of Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, 030032, China
