Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Faculty of Science, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Sci Adv. 2022 Jun 17;8(24):eabm4389. doi: 10.1126/sciadv.abm4389. Epub 2022 Jun 15.
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.
无痕物理提示对于远程控制原位生产和实时给药在基于细胞的治疗中非常理想。然而，当前的光遗传学、磁遗传学或电遗传学设备需要复杂的电子设备、复杂的人工智能辅助软件以及外部能源供应来提供电力和控制。在这里，我们描述了一种自给自足的皮下按钮控制细胞植入物，只需反复轻轻按压覆盖在其上的皮肤即可提供动力。按下按钮会导致植入物嵌入式压电膜的瞬态经皮变形，在半渗透铂涂层细胞室内产生足够的低电压能量，以介导从工程电敏感人细胞中快速释放生物制药。通过改变手指按压刺激的频率和持续时间来微调释放。作为概念验证，我们证明了通过手指压力激活皮下植入物可以恢复 1 型糖尿病小鼠模型的正常血糖水平。自给自足的按钮设备可能为患者提供一种新的便利性，以控制他们的基于细胞的治疗。
