RESUMO
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-1ß, 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.
Assuntos
Hidrogéis , Silicones , Animais , Imunidade Inata , Impressão Tridimensional , Próteses e Implantes , RatosRESUMO
BACKGROUND: Oral hairy leukoplakia (OHL) is an EBV-associated condition of the oral mucosa, which is often painless. It is found predominantly in HIV-positive patients and is considered a clinical indicator of immunosuppression. OHL has rarely been described in HIV-negative patients, being found most often in association with iatrogenic immunosuppression. OHL induced by topical steroids remains extremely rare. PATIENTS AND METHODS: An 81-year-old HIV-negative woman, treated for 3 months with topical steroids for oral lichen planus, developed an asymptomatic white, corrugated, non-removable plaque with vertical folds on the lateral edge of the tongue. Associated oral candidiasis was noted. Based upon histological findings and in situ hybridisation showing numerous EBV-infected epithelial cells, a diagnosis of oral hairy leucoplakia was made. DISCUSSION AND CONCLUSION: To our knowledge, we report herein only the second recorded case of OHL induced strictly by topical steroids. Self-medication and poor adherence to dosage recommendations were noted in the patient's medical history. Physicians must be aware of the rare but nevertheless possible adverse events associated with topical steroid use, particularly when such medication is prescribed over a long period for inflammatory diseases of the oral mucosa.
