Synthetic Biology and Soft Robotics in Biohybrid Kidney Replacement: A Conceptual Framework and Translational Roadmap

Abstract

ABSTRACT Background Chronic kidney disease necessitates safer, more continuous kidney replacement therapies (KRT), yet current dialysis and transplantation are constrained by intermittent treatment, organ scarcity, and immunosuppression‐related complications. Methods This conceptual narrative review examines the potential integration of synthetic biology and soft robotics within a biohybrid KRT framework. We define a cyborg nephron as an engineered functional unit coupling living renal/vascular cells with compliant mechanical and fluidic interfaces, organized as a Modular Renal Assist Device (MRAD) with separable filtration, tubular transport, endocrine support, and control modules. Technology readiness levels (TRL) were applied to distinguish established, preclinical, and conceptual components. Results Available evidence supports several individual components including cell‐based renal bioreactors, microphysiological models, endothelialized blood‐contacting surfaces, passive membranes, soft micropumps, and wireless sensing (TRL 3–5). Conversely, autonomous renal gene circuits, active immunoisolation, durable vascular integration, and fully implanted closed‐loop control remain predominantly preclinical or conceptual (TRL 1–2). Major barriers include thrombosis, oxygen delivery, cell maturation, genetic stability, mechanical fatigue, power demands, cybersecurity, and regulation of combined living‐device products. Conclusions The cyborg nephron represents a hypothesis‐generating research framework rather than a near‐term clinical solution. Staged validation through modular development, conservative safety design, and comparison with simpler alternatives is essential before integrated preclinical testing can be justified.