Department of Bioengineering, University of Utah, Salt Lake City, UT, USA.
Prog Brain Res. 2011;194:167-80. doi: 10.1016/B978-0-444-53815-4.00009-1.
A consistent feature of the foreign body response (FBR), irrespective of the type of implant, is persistent inflammation at the biotic-abiotic interface signaled by biomarkers of macrophage/microglial activation. Since macrophage-secreted factors shape the foreign body reaction, implant designs that reduce macrophage activation should improve biocompatibility and, with regard to recording devices, should improve reliability and longevity. At present, it is unclear whether the goal of seamless integration is possible or whether electrode developers can modulate specific aspects of the FBR by intentionally manipulating the constitutive properties of the implant. To explore this area, we studied the chronic brain FBR to planar solid silicon microelectrode arrays and planar lattice arrays with identical penetrating profiles but with reduced surface area in rats after an 8-week indwelling period. Using quantitative immunohistochemistry, we found that presenting less surface area after equivalent iatrogenic injury is accompanied by significantly less persistent macrophage activation, decreased blood brain barrier leakiness, and reduced neuronal cell loss. Our findings show that it is possible for implant developers to modulate specific aspects of the FBR by intentionally manipulating the constitutive properties of the implant. Our results also support the theory that the FBR to implanted electrode arrays, and likely other implants, can be explained by the presence of macrophages at the biotic-abiotic interface, which act as a sustained delivery source of bioactive agents that diffuse into the adjacent tissue and shape various features of the brain FBR. Further, our findings suggest that one method to improve the recording consistency and lifetime of implanted microelectrode arrays is to design implants that reduce the amount of macrophage activation at the biotic-abiotic interface and/or enhance the clearance or impact of their released factors.
异物反应（FBR）的一个一致特征是，无论植入物的类型如何，在生物 - 非生物界面都会持续存在炎症，这由巨噬细胞/小胶质细胞激活的生物标志物信号发出。由于巨噬细胞分泌的因子会影响异物反应，因此减少巨噬细胞激活的植入物设计应能提高生物相容性，而就记录设备而言，应能提高可靠性和使用寿命。目前，尚不清楚无缝集成的目标是否可行，或者电极开发者是否可以通过有意操纵植入物的固有特性来调节异物反应的特定方面。为了探索这一领域，我们研究了慢性大脑 FBR 对平面固态硅微电极阵列和平面晶格阵列的反应，这些阵列在 8 周的留置期后具有相同的穿透轮廓，但表面积减小。使用定量免疫组织化学，我们发现，在等效医源性损伤后呈现出较小的表面积会伴随着明显较少的持续巨噬细胞激活、降低血脑屏障通透性和减少神经元细胞丢失。我们的研究结果表明，植入物开发者可以通过有意操纵植入物的固有特性来调节异物反应的特定方面。我们的研究结果还支持这样一种理论，即植入电极阵列的异物反应（以及可能的其他植入物）可以通过生物 - 非生物界面处的巨噬细胞来解释，巨噬细胞作为生物活性物质的持续输送源，这些物质扩散到相邻组织中并塑造了大脑 FBR 的各种特征。此外，我们的研究结果表明，一种提高植入微电极阵列记录一致性和寿命的方法是设计减少生物 - 非生物界面处巨噬细胞激活量的植入物，和/或增强其释放因子的清除或影响。
