Optimized biomechanical design of a tissue engineered pulsatile Fontan conduit.

Children with congenital heart defects increasingly survive to adulthood, but the non-physiological Fontan circulation imposed by current surgical palliation leads to significant sequelae and reduced lifespan. Restoring subpulmonic pumping function remains a long-standing goal, and there have been several attempts using regenerative medicine approaches. These efforts have lacked biomechanical rigor, however, and have not achieved the requisite functionality. Here, we introduce an analytically based framework that grounds pulsatile conduit design in biomechanical principles, coupling the architecture and properties of a passive matrix with embedded myofibers to optimize performance within pediatric anatomical constraints. Parametric exploration of matrix properties and myofiber orientations yields biomechanically feasible designs. Sensitivity analyses demonstrate design robustness and highlight parameters critical for reproducible biomanufacturing and surgical implementation. To illustrate clinical potential, a patient-specific lumped-parameter hemodynamic model shows that an optimized pulsatile conduit can generate physiologically meaningful pressures and flows and outperform passive grafts.