State Key Laboratory of Transvascular Implantation Devices, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China.
MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, P. R. China.
Nat Commun. 2024 Aug 30;15(1):7526. doi: 10.1038/s41467-024-52023-z.
Polymeric elastomers are extensively employed to fabricate implantable medical devices. However, implantation of the elastomers can induce a strong immune rejection known as the foreign body response (FBR), diminishing their efficacy. Herein, we present a group of immunocompatible elastomers, termed easy-to-synthesize vinyl-based anti-FBR dense elastomers (EVADE). EVADE materials effectively suppress the inflammation and capsule formation in subcutaneous models of rodents and non-human primates for at least one year and two months, respectively. Implantation of EVADE materials significantly reduces the expression of inflammation-related proteins S100A8/A9 in adjacent tissues compared to polydimethylsiloxane. We also show that inhibition or knockout of S100A8/A9 leads to substantial attenuation of fibrosis in mice, suggesting a target for fibrosis inhibition. Continuous subcutaneous insulin infusion (CSII) catheters constructed from EVADE elastomers demonstrate significantly improved longevity and performance compared to commercial catheters. The EVADE materials reported here may enhance and extend function in various medical devices by resisting the local immune responses.
聚合物弹性体被广泛用于制造可植入的医疗设备。然而，弹性体的植入会引起强烈的免疫排斥反应，即异物反应（FBR），从而降低其疗效。在这里，我们提出了一组免疫相容性弹性体，称为易于合成的基于乙烯基的抗 FBR 致密弹性体（EVADE）。EVADE 材料在啮齿动物和非人类灵长类动物的皮下模型中分别有效地抑制了炎症和囊形成，至少持续一年零两个月。与聚二甲基硅氧烷相比，EVADE 材料的植入显著降低了邻近组织中与炎症相关的蛋白质 S100A8/A9 的表达。我们还表明，S100A8/A9 的抑制或敲除会导致小鼠纤维化的大量衰减，提示纤维化抑制的靶点。由 EVADE 弹性体制成的连续皮下胰岛素输注（CSII）导管与商业导管相比，显示出显著改善的耐久性和性能。这里报道的 EVADE 材料可能通过抵抗局部免疫反应来增强和延长各种医疗器械的功能。
