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

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.