A Self-Powered Optogenetic System for Implantable Blood Glucose Control

Abstract

Diabetes treatment and rehabilitation are usually a lifetime process. Optogenetic engineered designer cell-therapy holds great promise in regulating blood glucose homeostasis. However, portable, sustainable, and long-term energy supplementation has previously presented a challenge for the use of optogenetic stimulation in vivo. Herein, we purpose a self-powered optogenetic system (SOS) for implantable blood glucose control. The SOS consists of a biocompatible far-red light (FRL) source, FRL-triggered transgene-expressing cells, a power management unit, and a flexible implantable piezoelectric nanogenerator (i-PENG) to supply long-term energy by converting biomechanical energy into electricity. Our results show that this system can harvest energy from body movement and power the FRL source, which then significantly enhanced production of a short variant of human glucagon-like peptide 1 (shGLP-1) in vitro and in vivo. Indeed, diabetic mice equipped with the SOS showed rapid restoration of blood glucose homeostasis, improved glucose, and insulin tolerance. Our results suggest that the SOS is sufficiently effective in self-powering the modulation of therapeutic outputs to control glucose homeostasis and, furthermore, present a new strategy for providing energy in optogenetic-based cell therapy.

Optogenetic-controlled immunotherapeutic designer cells for post-surgical cancer immunotherapy

“…Beyond its potential for cancer therapy, the engineered living cell factory cells that we loaded into implants should be easily adaptable for remote control expression and secretion of other protein drugs including enzymes, peptide hormones, vaccines, and even antibodies for treating various diseases. For example, chassis cells (e.g., mesenchymal stem cells) loaded in scaffolds could be engineered to produce urate oxidase for treating gout 38 , insulin or human glucagon-like peptide 1 for treating diabetes 39 , 40 , cancer vaccines for stimulating immature dendritic cells (DCs) and naive T cells 41 , erythropoietin for treating anemia 42 , interferons for treating virus infection 43 , and even monoclonal antibodies (e.g., anti-PDL-1) 44 or immune checkpoint inhibitors for the treatment of cancer 45 , 46 . These ideas advance progress towards the living cell factory concept and this robust platform can be harnessed for driving long-term and on-demand production of therapeutic outputs for treating different diseases in a traceless remote-controllable defined manner.…”

Implantable Triboelectric Nanogenerators for Self‐Powered Cardiovascular Healthcare

“…[182][183][184][185][186][187][188] Thinking positively, we expect an influx of exciting innovations within the world of I-TENGs, whether in the realm of cardiology or in further aspects of personalized healthcare. [189][190][191][192][193][194][195][196][197][198][199][200][201][202] The world of biotechnology should follow the suit of these previous studies and intensify work to discover affordable and reliable progress in cardiac monitoring.…”

Wireless Self‐Powered Optogenetic System for Long‐Term Cardiac Neuromodulation to Improve Post‐MI Cardiac Remodeling and Malignant Arrhythmia

“…[27] The advanced technology of nanogenerators (TENG or piezoelectric nanogenerators) has provided a great chance to convert biomechanical energy in the human body into electricity for powering wireless optical systems. [32,33,[46][47][48] Thus, in the present study, we developed a wireless self-powered optogenetic system suitable for wireless cardiac sympathetic modulation in awake freely moving canines. The wireless self-powered optical system based on a TENG is powered by energy harvested from body motion and realized effective optical illumination that is required for optogenetic neuromodulation.…”