Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
Biomaterials. 2010 May;31(13):3479-91. doi: 10.1016/j.biomaterials.2010.01.074. Epub 2010 Feb 6.
Current strategies to limit macrophage adhesion, fusion and fibrous capsule formation in the foreign body response have focused on modulating material surface properties. We hypothesize that topography close to biological scale, in the micron and nanometric range, provides a passive approach without bioactive agents to modulate macrophage behavior. In our study, topography-induced changes in macrophage behavior was examined using parallel gratings (250 nm-2 mum line width) imprinted on poly(epsilon-caprolactone) (PCL), poly(lactic acid) (PLA) and poly(dimethyl siloxane) (PDMS). RAW 264.7 cell adhesion and elongation occurred maximally on 500 nm gratings compared to planar controls over 48 h. TNF-alpha and VEGF secretion levels by RAW 264.7 cells showed greatest sensitivity to topographical effects, with reduced levels observed on larger grating sizes at 48 h. In vivo studies at 21 days showed reduced macrophage adhesion density and degree of high cell fusion on 2 mum gratings compared to planar controls. It was concluded that topography affects macrophage behavior in the foreign body response on all polymer surfaces examined. Topography-induced changes, independent of surface chemistry, did not reveal distinctive patterns but do affect cell morphology and cytokine secretion in vitro, and cell adhesion in vivo particularly on larger size topography compared to planar controls.
目前，限制异物反应中巨噬细胞黏附、融合和纤维囊形成的策略主要集中在调节材料表面特性上。我们假设，接近生物尺度的形貌（微米和纳米级）为调节巨噬细胞行为提供了一种无需生物活性剂的被动方法。在我们的研究中，使用压印在聚己内酯（PCL）、聚乳酸（PLA）和聚二甲基硅氧烷（PDMS）上的平行光栅（250nm-2μm 线宽）研究了形貌诱导的巨噬细胞行为变化。与平面对照相比，RAW 264.7 细胞在 48 小时内最大程度地黏附在 500nm 的光栅上并伸长。RAW 264.7 细胞分泌的 TNF-α和 VEGF 水平对形貌效应最敏感，48 小时时观察到大尺寸光栅的水平降低。21 天的体内研究表明，与平面对照相比，2μm 光栅上的巨噬细胞黏附密度和高度融合细胞的程度降低。结论是，在所有研究的聚合物表面上，形貌都会影响异物反应中的巨噬细胞行为。形貌诱导的变化与表面化学无关，没有表现出独特的模式，但确实会影响细胞形态和细胞因子分泌体外，以及细胞黏附体内尤其是与平面对照相比，较大尺寸的形貌。
