Lipid Deposition Profiles Influence Foreign Body Responses.
Lipid Deposition Profiles Influence Foreign Body Responses.
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脂质沉积概况影响异物反应。
DOI：
10.1002/adma.202205709
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Hanak,
中科院分区：
文献类型：
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作者：
Schreib,ChristianC;Jarvis,MariaI;Terlier,Tanguy;Goell,Jacob;Mukherjee,Sudip;Doerfert,MichaelD;Wilson,TaylorAnne;Beauregard,Michael;Martins,KevinN;Lee,Jared;SanchezSolis,LeonardoD;Vazquez,Esperanza;Oberli,MatthiasA;Hanak,
纤维化仍然是植入生物医学器械失效的重要原因，并且植入物表面上蛋白质的早期吸收已被证明是一个关键的诱发因素。然而，脂质也可以调节免疫活性，它们的存在也可能导致生物材料诱导的异物反应（FBR）和纤维化。本文证明，植入物上脂质的表面呈现通过影响免疫细胞对材料的反应及其产生的炎症/抑制极化来影响FBR。采用飞行时间二次离子质谱（ToF‐西姆斯）来表征用免疫调节小分子进行化学表面改性的植入物上的脂质沉积。发现多种免疫抑制磷脂（磷脂酰胆碱、磷脂酰肌醇、磷脂酰乙醇胺和鞘磷脂）均优先存款在小鼠中具有抗FBR表面修饰的植入物上。值得注意的是，一组11种脂肪酸在未经修改的植入设备上富集，这些设备在小鼠和人类中都失败了，突出了跨物种的相关性。还发现磷脂沉积上调小鼠巨噬细胞中抗炎基因的转录，而脂肪酸沉积刺激促炎基因的表达。这些结果为如何改进生物材料和医疗器械的设计以减轻生物材料诱导的FBR和纤维化提供了进一步的见解。
Fibrosis remains a significant cause of failure in implanted biomedical devices and early absorption of proteins on implant surfaces has been shown to be a key instigating factor. However, lipids can also regulate immune activity and their presence may also contribute to biomaterial‐induced foreign body responses (FBR) and fibrosis. Here it is demonstrated that the surface presentation of lipids on implant affects FBR by influencing reactions of immune cells to materials as well as their resultant inflammatory/suppressive polarization. Time‐of‐flight secondary ion mass spectroscopy (ToF‐SIMS) is employed to characterize lipid deposition on implants that are surface‐modified chemically with immunomodulatory small molecules. Multiple immunosuppressive phospholipids (phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine, and sphingomyelin) are all found to deposit preferentially on implants with anti‐FBR surface modifications in mice. Significantly, a set of 11 fatty acids is enriched on unmodified implanted devices that failed in both mice and humans, highlighting relevance across species. Phospholipid deposition is also found to upregulate the transcription of anti‐inflammatory genes in murine macrophages, while fatty acid deposition stimulated the expression of pro‐inflammatory genes. These results provide further insights into how to improve the design of biomaterials and medical devices to mitigate biomaterial material‐induced FBR and fibrosis.