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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月2日

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  • Malak Kawan,
  • Amy Jin,
  • Zixuan Lu,
  • Sydney Swedick,
  • Salim El-Hadwe,
  • Margaux O. A. Forner,
  • Sagnik Middya,
  • Sam Hilton,
  • Nataly Hastings,
  • Moleca M. Ghannam,
  • Chaeyeon Lee,
  • Mark N. Kotter,
  • Róisín M. Owens,
  • George G. Malliaras,
  • Alejandro Carnicer-Lombarte,
  • Damiano G. Barone

摘要

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.