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首页> 外文期刊>Journal of materials science >A self-cleaning, mechanically robust membrane for minimizing the foreign body reaction: towards extending the lifetime of sub-Q glucose biosensors
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A self-cleaning, mechanically robust membrane for minimizing the foreign body reaction: towards extending the lifetime of sub-Q glucose biosensors

机译：一种自清洁，机械坚固的膜，可最大程度减少异物反应：延长Sub-Q葡萄糖生物传感器的使用寿命

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Long-term, subcutaneously implanted continuous glucose biosensors have the potential to improve diabetes management and reduce associated complications. However, the innate foreign body reaction (FBR) both alters the local glucose concentrations in the surrounding tissues and compromises glucose diffusion to the biosensor due to the recruitment of high-metabolizing inflammatory cells and the formation of a dense, collagenous fibrous capsule. Minimizing the FBR has mainly focused on passively antifouling materials that reduce initial cellular attachment, including poly(ethylene glycol) (PEG). Instead, the membrane reported herein utilizes an actively antifouling or self-cleaning mechanism to inhibit cellular attachment through continuous, cyclic deswelling/reswelling in response to normal temperature fluctuations of the subcutaneous tissue. This thermoresponsive double network (DN) membrane is based on N-isopropylacrylamide (NIPAAm) and 2-acrylamido-2-methylpropane sulfonic acid (AMPS) (75:25 and 100:0 NIPAAm:AMPS in the 1st and 2nd networks, respectively; DN-25%). The extent of the FBR reaction of a subcutaneously implanted DN-25% cylindrical membrane was evaluated in rodents in parallel with a PEG-diacrylate (PEG-DA) hydrogel as an established benchmark biocompatible control. Notably, the DN-25% implants were more than 25x stronger and tougher than the PEG-DA implants while maintaining a modulus near that of subcutaneous tissue. From examining the FBR at 7, 30 and 90 days after implantation, the thermoresponsive DN-25% implants demonstrated a rapid healing response and a minimal fibrous capsule (similar to 20-25 mu m), similar to the PEG-DA implants. Thus, the dynamic self-cleaning mechanism of the DN-25% membranes represents a new approach to limit the FBR while achieving the durability necessary for long-term implantable glucose biosensors.[GRAPHICS].
机译：长期皮下植入的连续葡萄糖生物传感器具有改善糖尿病管理和减少相关并发症的潜力。但是，由于高代谢性炎症细胞的募集和致密胶原纤维囊的形成，先天异物反应（FBR）既改变了周围组织中的局部葡萄糖浓度，又损害了葡萄糖向生物传感器的扩散。使FBR最小化主要集中于减少初始细胞附着的被动防污材料，包括聚（乙二醇）（PEG）。相反，本文报道的膜利用主动防污或自清洁机制来响应于皮下组织的正常温度波动通过连续的，周期性的溶胀/再膨胀来抑制细胞附着。这种热响应性双网络（DN）膜基于N-异丙基丙烯酰胺（NIPAAm）和2-丙烯酰胺基-2-甲基丙烷磺酸（AMPS）（在第一和第二网络中分别为75:25和100：0 NIPAAm：AMPS）； DN-25％）。皮下植入的DN-25％圆柱形膜的FBR反应程度在啮齿动物中与PEG-二丙烯酸酯（PEG-DA）水凝胶平行进行评估，以此作为已建立的基准生物相容性对照。值得注意的是，DN-25％植入物的强度和韧性比PEG-DA植入物强25倍以上，同时保持的模量接近皮下组织。通过在植入后第7、30和90天检查FBR，与PEG-DA植入物相似，热敏性DN-25％植入物显示出快速的愈合反应和最小的纤维囊（类似于20-25μm）。因此，DN-25％膜的动态自清洁机制代表了一种限制FBR的新方法，同时实现了长期可植入葡萄糖生物传感器所必需的耐用性。

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