Chen E Y, Chu S, Gov L, Kim Y K, Lodoen M B, Tenner A J, Liu W F
Department of Chemical Engineering and Materials Science, University of California, Irvine.
The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine.
J Mater Chem B. 2017 Feb 28;5(8):1574-1584. doi: 10.1039/C6TB02269C. Epub 2017 Jan 10.
Biocompatibility is a major concern for developing biomaterials used in medical devices, tissue engineering and drug delivery. Poly(lactic-co-glycolic acid) (PLGA) is one of the most widely used biodegradable materials, yet still triggers a significant foreign body response that impairs healing. Immune cells including macrophages respond to the implanted biomaterial and mediate the host response, which can eventually lead to device failure. Previously in our laboratory, we found that CD200, an immunomodulatory protein, suppressed macrophage inflammatory activation in vitro and reduced local immune cell infiltration around a biomaterial implant. While in our initial study we used polystyrene as a model material, here we investigate the effect of CD200 on PLGA, a commonly used biomaterial with many potential clinical applications. We fabricated PLGA with varied geometries, modified their surfaces with CD200, and examined macrophage cytokine secretion and phagocytosis. We found that CD200 suppressed secretion of the pro-inflammatory cytokine TNF-α and enhanced secretion of the anti-inflammatory cytokine IL-10, suggesting a role for CD200 in promoting wound healing and tissue remodeling. In addition, we found that CD200 increased phagocytosis in both murine macrophages and human monocytes. Together, these data suggest that modification with CD200 leads to a response that simultaneously prevents inflammation and enhances phagocytosis. This immunomodulatory feature may be used as a strategy to mitigate inflammation or deliver drugs or anti-inflammatory agents targeting macrophages.
生物相容性是开发用于医疗设备、组织工程和药物递送的生物材料时的一个主要关注点。聚乳酸-乙醇酸共聚物（PLGA）是使用最广泛的可生物降解材料之一，但仍会引发显著的异物反应，从而损害愈合过程。包括巨噬细胞在内的免疫细胞会对植入的生物材料做出反应并介导宿主反应，最终可能导致设备失效。此前在我们实验室，我们发现免疫调节蛋白CD200在体外可抑制巨噬细胞的炎症激活，并减少生物材料植入物周围的局部免疫细胞浸润。在我们最初的研究中，我们使用聚苯乙烯作为模型材料，而在此我们研究CD200对PLGA（一种具有许多潜在临床应用的常用生物材料）的影响。我们制备了具有不同几何形状的PLGA，用CD200对其表面进行修饰，并检测巨噬细胞细胞因子的分泌和吞噬作用。我们发现CD200抑制促炎细胞因子TNF-α的分泌，并增强抗炎细胞因子IL-10的分泌，这表明CD200在促进伤口愈合和组织重塑中发挥作用。此外，我们发现CD200在小鼠巨噬细胞和人类单核细胞中均增加了吞噬作用。总之，这些数据表明用CD200进行修饰会引发一种既能预防炎症又能增强吞噬作用的反应。这种免疫调节特性可作为减轻炎症或递送靶向巨噬细胞的药物或抗炎剂的一种策略。
