Integrating bioelectronics with cell-based synthetic biology

Biohybrid devices based on engineered cells interfaced with bioelectronics represent a promising union where the strengths of each field can be synergistically combined, resulting in constructs with properties that are not otherwise achievable. Recent progress in biomaterials and cell-based synthetic biology has resulted in cells that can be remotely triggered via multiple modalities and can access a number of cellular pathways to achieve complex sensing and biomolecule production tasks. Although these living cells can be deployed as next-generation diagnostics and cell-based therapies, they are limited by the fundamental boundaries of biology. Bioelectronics, conversely, has been engineered to leverage the strengths of established computational hardware and software, integrates multiple inputs of biometric and external data, and allows communication over long distances. However, bioelectronics often requires considerable power to perform complex tasks and lacks the specificity and adaptability of cells and tissues. The parallel advances in synthetic biology, biomaterials and bioelectronics therefore present new opportunities in devices for regulated cell therapies, diagnostic tools and next-generation robotics. In this Review, we discuss the enabling mechanisms of communication between engineered cells and bioelectronics platforms, describe the approaches and challenges in assembling and deploying such systems, and highlight recent prototypes. The continued advancement in cell support systems and both internal and external closed-loop control suggest forthcoming breakthrough opportunities for biohybrid bioelectronics.