Reducing foreign body reaction via neural interfaces coated with iPSC-derived neuronal membranes

Abstract Advancements in neural interfaces have been hindered by the foreign body reaction (FBR), which drives inflammation and fibrotic encapsulation of implanted probes, limiting long-term performance. Biomimetic strategies that better match biological form and mechanics have recently emerged to address this challenge. Here, we mitigate FBR by incorporating human iPSC-derived neuronal membranes as biological mediators between device and host tissue, reducing inflammation and fibrosis while improving long-term stability and signal quality. We integrate flexible electronics with bioengineering to extract and assemble human iPSC-derived neuronal membranes, first characterizing their structural integrity and electrical sealing properties in vitro. In vivo experiments in rats show that subdurally implanted membrane-based biohybrid neural interfaces significantly reduce FBR at day 28 compared to controls, while preserving high signal-to-noise ratios. Moreover, chronic recordings in freely moving, awake animals demonstrate stable single-neuron activity for up to two months. The neuronal lipid layer provides a controlled increase in impedance while enabling reliable long-term recording stability. These results highlight the promise of cell-derived, cell-free biohybrid neural interfaces to enhance implant integration and function. Modulating membrane lipid and protein composition may further enable tailoring to specific anatomical and pathological contexts.