Traceless physical cues are desirable for remote control of the in situ production and real-time dosing of biopharmaceuticals in cell-based therapies. However, current optogenetic, magnetogenetic, or electrogenetic devices require sophisticated electronics, complex artificial intelligence–assisted software, and external energy supplies for power and control. Here, we describe a self-sufficient subcutaneous push button–controlled cellular implant powered simply by repeated gentle finger pressure exerted on the overlying skin. Pushing the button causes transient percutaneous deformation of the implant’s embedded piezoelectric membrane, which produces sufficient low-voltage energy inside a semi-permeable platinum-coated cell chamber to mediate rapid release of a biopharmaceutical from engineered electro-sensitive human cells. Release is fine-tuned by varying the frequency and duration of finger-pressing stimulation. As proof of concept, we show that finger-pressure activation of the subcutaneous implant can restore normoglycemia in a mouse model of type 1 diabetes. Self-sufficient push-button devices may provide a new level of convenience for patients to control their cell-based therapies.

中文翻译：

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从压电激活的皮下细胞植入物中自主按钮控制的快速胰岛素释放

在基于细胞的治疗中，对于远程控制原位生产和生物药物的实时给药，需要无痕物理线索。然而，当前的光遗传、磁遗传或电遗传设备需要复杂的电子设备、复杂的人工智能辅助软件以及用于电源和控制的外部能源供应。在这里，我们描述了一种自给自足的皮下按钮控制的细胞植入物，该植入物仅由施加在覆盖皮肤上的反复轻柔手指压力提供动力。按下按钮会导致植入物嵌入的压电膜发生瞬时经皮变形，从而在半渗透性铂涂层细胞室内产生足够的低压能量，以促进生物药物从工程电敏人体细胞中快速释放。通过改变手指按压刺激的频率和持续时间来微调释放。作为概念证明，我们表明皮下植入物的手指压力激活可以恢复 1 型糖尿病小鼠模型中的血糖正常。自给自足的按钮设备可以为患者控制他们的细胞疗法提供新的便利。