Cavendish Laboratory, Physics Department, University of Cambridge, UK; John van Geest Centre for Brain Repair, University of Cambridge, UK.
Cavendish Laboratory, Physics Department, University of Cambridge, UK.
Biomaterials. 2014 Apr;35(13):3919-25. doi: 10.1016/j.biomaterials.2014.01.038. Epub 2014 Feb 11.
Devices implanted into the body become encapsulated due to a foreign body reaction. In the central nervous system (CNS), this can lead to loss of functionality in electrodes used to treat disorders. Around CNS implants, glial cells are activated, undergo gliosis and ultimately encapsulate the electrodes. The primary cause of this reaction is unknown. Here we show that the mechanical mismatch between nervous tissue and electrodes activates glial cells. Both primary rat microglial cells and astrocytes responded to increasing the contact stiffness from physiological values (G' ∼ 100 Pa) to shear moduli G' ≥ 10 kPa by changes in morphology and upregulation of inflammatory genes and proteins. Upon implantation of composite foreign bodies into rat brains, foreign body reactions were significantly enhanced around their stiff portions in vivo. Our results indicate that CNS glial cells respond to mechanical cues, and suggest that adapting the surface stiffness of neural implants to that of nervous tissue could minimize adverse reactions and improve biocompatibility.
植入体内的设备会因异物反应而被包裹。在中枢神经系统 (CNS) 中，这可能导致用于治疗疾病的电极失去功能。在 CNS 植入物周围，神经胶质细胞被激活，发生神经胶质增生，最终包裹电极。这种反应的主要原因尚不清楚。在这里，我们表明，神经组织和电极之间的力学不匹配会激活神经胶质细胞。原代大鼠小胶质细胞和星形胶质细胞对接触刚度从生理值 (G' ∼ 100 Pa) 增加到剪切模量 G' ≥ 10 kPa 的反应是通过形态变化和炎症基因和蛋白的上调来实现的。在将复合材料异物植入大鼠大脑后，其坚硬部分周围的异物反应在体内明显增强。我们的结果表明，CNS 神经胶质细胞对机械刺激有反应，并表明使神经植入物的表面刚度与神经组织相适应可以最小化不良反应并提高生物相容性。
