Blood-catalyzed n-doped polymers for reversible optical neural control.
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| Title: | Blood-catalyzed n-doped polymers for reversible optical neural control. |
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| Authors: | Samal, Sanket (AUTHOR), Xiao, Shulan (AUTHOR), Nelson, Samantha (AUTHOR), Kolhe, Om (AUTHOR), Khan, Hammad F. (AUTHOR), Matin, Meisam Habibi (AUTHOR), Lee, Won-June (AUTHOR), Ahmed, Mustafa (AUTHOR), Wang, Decheng (AUTHOR), Wang, Tianqi (AUTHOR), Pikes, Tyler (AUTHOR), Scott, Alicia N. (AUTHOR), Rodriguez, J. Alejandra (AUTHOR), Olson, Matthew R. (AUTHOR), Deng, Qing (AUTHOR), Parkinson, Elizabeth I. (AUTHOR), Rochet, Jean-Christophe (AUTHOR), Jayant, Krishna (AUTHOR), Mei, Jianguo (AUTHOR) |
| Source: | Science. 4/2/2026, Vol. 392 Issue 6793, p1-11. 11p. |
| Subjects: | Conducting polymers, Hemoproteins, Optical control, Neuromodulation, Brain-computer interfaces, Near infrared radiation, Polymerization, Biomedical materials |
| Abstract: | Biocompatible integration of synthetic materials with living tissue remains a major challenge for bioelectronics. In this case, substrate-free conducting polymer (CP) interfaces could help bridge this gap. We report in vivo assembly of n-doped poly(benzodifurandione) (n-PBDF) using whole blood–catalyzed polymerization in awake zebrafish and mice. This approach leverages endogenous catalysts, specifically hemoproteins, to form stable, thermally and ionically sensitive CP networks, ensuring long-term compatibility throughout the lifespan. We showcase the impact of this interface through reversible, cellular, and subcellular neuromodulation using near-infrared (NIR) light, including in vivo polymerized n-PBDF. Electrophysiological studies confirmed that n-PBDF alters intrinsic sodium ion channel excitability, and NIR light stimulation amplifies this modulation through thermoionic-induced shunting, providing on-demand, millisecond-scale reversible inhibitory control of excitability, a feature recapitulated in actively behaving mice. Editor's summary: In addition to the challenges of developing effective materials for in vivo use, manufacturing such materials must avoid toxic components. For some applications, there may even be benefits to doing the synthesis inside of the target organism. Samal et al. describe the formation of a conductive polymer through oxidation with various natural catalysts, including heme, red blood cells, and whole blood samples (see the Perspective by Antognazza and Lanzani). The authors demonstrated reversible cellular and subcellular neuromodulation through near-infrared light in live animals using this material with no observable toxicity or behavioral deficits. —Marc S. Lavine INTRODUCTION: Engineering synthetic materials that integrate with living tissue is central to advancing bioelectronic medicine and neurotechnology. Conducting polymers (CPs) are promising candidates, combining electrical conductivity, compliance, and biocompatibility for long-term neural interfaces. Yet, most CP biointerfaces rely on top-down fabrication and implantation, leading to poor integration with dynamic tissues and degraded performance. The development of n-type CPs that assemble directly in vivo offers a transformative, substrate-free strategy for stable electrical interfaces. Although in vivo assembly of p-type CPs, such as polyaniline and polythiophenes, has advanced, controllable neuromodulation with n-type systems remains unexplored owing to missing biocompatible polymerization strategies. Overcoming this barrier could enable injectable, lifelong, and on-demand platforms for millisecond-precision neural modulation, addressing an urgent need in neuroscience, neuromodulation, and minimally invasive bioelectronics. RATIONALE: To close this gap, we harnessed endogenous enzymatic activity—specifically, hemoprotein-catalyzed oxidative polymerization—to assemble the n-doped conducting polymer poly(benzodifurandione) (n-PBDF) in vivo. Unlike external initiator methods, our approach uses natural hemoglobin (Hb) and myoglobin to catalyze polymerization and in situ doping, ensuring physiological compatibility with spatial and temporal control. n-PBDF's strong near-infrared (NIR) absorption, ionic conductivity, and long-term stability distinctively position it for reversible, light-triggered neuromodulation. We hypothesized that its photothermal and ionic properties would permit nongenetic, on-demand inhibition of neural activity under NIR stimulation. We further aimed to confirm its biocompatibility and integration across complex tissues, including zebrafish embryos and mammalian brains, while rigorously assessing behavioral and biocompatibility outcomes. RESULTS: Our experiments confirmed that hemoproteins efficiently catalyze n-PBDF assembly in living systems. In zebrafish embryos, the injection of the BDF monomer triggered a visible darkening of the yolk, signaling the formation of the polymer. Spectroscopy confirmed its chemical identity. Notably, embryos developed normally, moved naturally, and showed more than 80% survival after 1 week, with no behavioral deficits. In mice, injection of the monomer into the brain led to localized polymerization of n-PBDF. The material formed stable deposits without signs of inflammation, neural cell loss, or changes in animal behavior. Imaging and blood vessel assays supported its safety, whereas electrophysiological recordings revealed its effects: n-PBDF altered the activity of sodium and potassium channels, mechanisms critical for controlling neuronal firing. By pairing dendrite-targeted injections with two-photon NIR stimulation, we could reversibly silence neurons within milliseconds, a capability absent in p-type polymer systems. In vivo, this precise modulation translated into measurable, rapid behavioral effects. CONCLUSION: Whole blood–catalyzed n-PBDF polymerization yields a biocompatible, substrate-free neural interface with long-term functionality in living animals. Its combined photothermal and ionic capacities support on-demand, reversible silencing at subcellular scales with low-power requirements without inducing toxicity, inflammation, or behavioral disruption. This versatile, ultrasoft electrode, synthesized and actuated in situ, offers a new paradigm for minimally invasive bioelectronic interfaces. In vivo–grown soft tissue–like electrical interfaces.: (A) Synthesis of n-PBDF using hemoprotein as catalyst. (B) No behavioral deficit was induced by the polymerization in zebrafish embryos and the mice neocortices. (C) Growth of n-PBDF in the brain forming neural interfaces. (D) Optically induced neural inhibition through n-PBDF. (E) Optical modulation of mice behavior with n-PBDF. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Biocompatible integration of synthetic materials with living tissue remains a major challenge for bioelectronics. In this case, substrate-free conducting polymer (CP) interfaces could help bridge this gap. We report in vivo assembly of n-doped poly(benzodifurandione) (n-PBDF) using whole blood–catalyzed polymerization in awake zebrafish and mice. This approach leverages endogenous catalysts, specifically hemoproteins, to form stable, thermally and ionically sensitive CP networks, ensuring long-term compatibility throughout the lifespan. We showcase the impact of this interface through reversible, cellular, and subcellular neuromodulation using near-infrared (NIR) light, including in vivo polymerized n-PBDF. Electrophysiological studies confirmed that n-PBDF alters intrinsic sodium ion channel excitability, and NIR light stimulation amplifies this modulation through thermoionic-induced shunting, providing on-demand, millisecond-scale reversible inhibitory control of excitability, a feature recapitulated in actively behaving mice. Editor's summary: In addition to the challenges of developing effective materials for in vivo use, manufacturing such materials must avoid toxic components. For some applications, there may even be benefits to doing the synthesis inside of the target organism. Samal et al. describe the formation of a conductive polymer through oxidation with various natural catalysts, including heme, red blood cells, and whole blood samples (see the Perspective by Antognazza and Lanzani). The authors demonstrated reversible cellular and subcellular neuromodulation through near-infrared light in live animals using this material with no observable toxicity or behavioral deficits. —Marc S. Lavine INTRODUCTION: Engineering synthetic materials that integrate with living tissue is central to advancing bioelectronic medicine and neurotechnology. Conducting polymers (CPs) are promising candidates, combining electrical conductivity, compliance, and biocompatibility for long-term neural interfaces. Yet, most CP biointerfaces rely on top-down fabrication and implantation, leading to poor integration with dynamic tissues and degraded performance. The development of n-type CPs that assemble directly in vivo offers a transformative, substrate-free strategy for stable electrical interfaces. Although in vivo assembly of p-type CPs, such as polyaniline and polythiophenes, has advanced, controllable neuromodulation with n-type systems remains unexplored owing to missing biocompatible polymerization strategies. Overcoming this barrier could enable injectable, lifelong, and on-demand platforms for millisecond-precision neural modulation, addressing an urgent need in neuroscience, neuromodulation, and minimally invasive bioelectronics. RATIONALE: To close this gap, we harnessed endogenous enzymatic activity—specifically, hemoprotein-catalyzed oxidative polymerization—to assemble the n-doped conducting polymer poly(benzodifurandione) (n-PBDF) in vivo. Unlike external initiator methods, our approach uses natural hemoglobin (Hb) and myoglobin to catalyze polymerization and in situ doping, ensuring physiological compatibility with spatial and temporal control. n-PBDF's strong near-infrared (NIR) absorption, ionic conductivity, and long-term stability distinctively position it for reversible, light-triggered neuromodulation. We hypothesized that its photothermal and ionic properties would permit nongenetic, on-demand inhibition of neural activity under NIR stimulation. We further aimed to confirm its biocompatibility and integration across complex tissues, including zebrafish embryos and mammalian brains, while rigorously assessing behavioral and biocompatibility outcomes. RESULTS: Our experiments confirmed that hemoproteins efficiently catalyze n-PBDF assembly in living systems. In zebrafish embryos, the injection of the BDF monomer triggered a visible darkening of the yolk, signaling the formation of the polymer. Spectroscopy confirmed its chemical identity. Notably, embryos developed normally, moved naturally, and showed more than 80% survival after 1 week, with no behavioral deficits. In mice, injection of the monomer into the brain led to localized polymerization of n-PBDF. The material formed stable deposits without signs of inflammation, neural cell loss, or changes in animal behavior. Imaging and blood vessel assays supported its safety, whereas electrophysiological recordings revealed its effects: n-PBDF altered the activity of sodium and potassium channels, mechanisms critical for controlling neuronal firing. By pairing dendrite-targeted injections with two-photon NIR stimulation, we could reversibly silence neurons within milliseconds, a capability absent in p-type polymer systems. In vivo, this precise modulation translated into measurable, rapid behavioral effects. CONCLUSION: Whole blood–catalyzed n-PBDF polymerization yields a biocompatible, substrate-free neural interface with long-term functionality in living animals. Its combined photothermal and ionic capacities support on-demand, reversible silencing at subcellular scales with low-power requirements without inducing toxicity, inflammation, or behavioral disruption. This versatile, ultrasoft electrode, synthesized and actuated in situ, offers a new paradigm for minimally invasive bioelectronic interfaces. In vivo–grown soft tissue–like electrical interfaces.: (A) Synthesis of n-PBDF using hemoprotein as catalyst. (B) No behavioral deficit was induced by the polymerization in zebrafish embryos and the mice neocortices. (C) Growth of n-PBDF in the brain forming neural interfaces. (D) Optically induced neural inhibition through n-PBDF. (E) Optical modulation of mice behavior with n-PBDF. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00368075 |
| DOI: | 10.1126/science.adu5500 |
