A temporally biosynchronized and physically transient peripheral nerve interface

Abstract

Peripheral nerve injury often leads to severe and persistent motor and sensory deficits, thereby markedly reducing quality of life. Peripheral nerve interfaces offer opportunities to facilitate functional restoration by interrogating neural activity and delivering electrical therapy. However, existing devices are typically not designed for long-term monitoring of injured nerves and are fabricated from non-degradable materials that require surgical removal. Here we present a temporally biosynchronized, physically transient and flexible peripheral nerve interface that enables stable monitoring of neural activity throughout the post-injury recovery process. Integrated with machine-learning-based decoding, the interface achieves excellent motor intention recognition using peripheral nerve signals in a rodent sciatic nerve injury model, outperforming signals recorded from the primary motor cortex. Moreover, the device enables continuous tracking of nerve regeneration and supports bidirectional signal transmission, providing a foundation for closed-loop rehabilitation. This work establishes a transient and biomimetic peripheral nerve interface with the potential to advance neuroregeneration monitoring and adaptive neurorehabilitation strategies.

Keywords

Neural interface / peripheral nerve injury / biodegradable electronics / rehabilitation medicine

References

[1] Faroni A.,Mobasseri S. A.,Kingham P. J.,Reid A. J.. Peripheral nerve regeneration: experimental strategies and future perspectives Adv. Drug Deliv. Rev. 2015 82-83 160 7

[2] Li R.,Li D.,Zhang H.,Wang J.,Li X.,Xiao J.. Growth factors-based therapeutic strategies and their underlying signaling mechanisms for peripheral nerve regeneration Acta Pharmacol. Sin. 2020 41 1289 300 PMC7608263

[3] Lopes B.,Sousa P.,Alvites R..et al. Peripheral nerve injury treatments and advances: one health perspective Int. J. Mol. Sci. 2022 23 918 PMC8779751

[4] Zhou W.,Rahman M. S. U.,Sun C..et al. Perspectives on the novel multifunctional nerve guidance conduits: from specific regenerative procedures to motor function rebuilding Adv. Mater. 2024 36 2307805

[5] Calvo M.,Bennett D. L.. The mechanisms of microgliosis and pain following peripheral nerve injury Exp. Neurol. 2012 234 271 82

[6] Taylor K. S.,Anastakis D. J.,Davis K. D.. Chronic pain and sensorimotor deficits following peripheral nerve injury Pain 2010 151 582 91

[7] Pan J.,Zhao M.,Yi X..et al. Acellular nerve grafts supplemented with induced pluripotent stem cell-derived exosomes promote peripheral nerve reconstruction and motor function recovery Bioact. Mater. 2022 15 272 87 PMC8935093

[8] Choi Y. S.,Hsueh Y.,Koo J..et al. Stretchable, dynamic covalent polymers for soft, long-lived bioresorbable electronic stimulators designed to facilitate neuromuscular regeneration Nat. Commun. 2020 11 5990 PMC7688647

[9] Stolze H.,Klebe S.,Baecker C..et al. Prevalence of gait disorders in hospitalized neurological patients Mov. Disord. 2004 20 89 94

[10] Asplund M.,Nilsson M.,Jacobsson A.,Von Holst H.. Incidence of traumatic peripheral nerve injuries and amputations in Sweden between 1998 and 2006 Neuroepidemiology 2009 32 217 28

[11] Valle G.,Katic Secerovic N.,Eggemann D..et al. Biomimetic computer-to-brain communication enhancing naturalistic touch sensations via peripheral nerve stimulation Nat. Commun. 2024 15 1151 PMC10879152

[12] Lemke S. M.,Ramanathan D. S.,Guo L.,Won S. J.,Ganguly K.. Emergent modular neural control drives coordinated motor actions Nat. Neurosci. 2019 22 1122 31 PMC6592763

[13] Miller W. C.,Speechley M.,Deathe B.. The prevalence and risk factors of falling and fear of falling among lower extremity amputees Arch. Phys. Med. Rehabil. 2001 82 1031 7

[14] Johnson E. O.,Soucacos P. N.. Nerve repair: experimental and clinical evaluation of biodegradable artificial nerve guides Injury 2008 39 30 6

[15] Manoukian O. S.,Baker J. T.,Rudraiah S..et al. Functional polymeric nerve guidance conduits and drug delivery strategies for peripheral nerve repair and regeneration J. Control. Release 2020 317 78 95

[16] Qian Y.,Lin H.,Yan Z.,Shi J.,Fan C.. Functional nanomaterials in peripheral nerve regeneration: scaffold design, chemical principles and microenvironmental remodeling Mater. Today 2021 51 165 87

[17] Calvey C.,Zhou W.,Stakleff K. S..et al. Short-term electrical stimulation to promote nerve repair and functional recovery in a rat model J. Hand Surg. 2015 40 314 22

[18] Jin F.,Li T.,Yuan T..et al. Physiologically self-regulated, fully implantable, battery-free system for peripheral nerve restoration Adv. Mater. 2021 33 2104175

[19] Maugeri G.,D'agata V.,Trovato B..et al. The role of exercise on peripheral nerve regeneration: from animal model to clinical application Heliyon 2021 7 e08281 PMC8571504

[20] Seo T. B.,Han I. S.,Yoon J.,Hong K.,Yoon S.,Namgung U.. Involvement of Cdc2 in axonal regeneration enhanced by exercise training in rats Med. Sci. Sports Exerc. 2006 38 1267 76

[21] Benabid A. L.,Costecalde T.,Eliseyev A..et al. An exoskeleton controlled by an epidural wireless brain-machine interface in a tetraplegic patient: a proof-of-concept demonstration Lancet Neurol. 2019 18 1112 22

[22] Lerner Z. F.,Damiano D. L.,Bulea T. C.. A lower-extremity exoskeleton improves knee extension in children with crouch gait from cerebral palsy Sci. Transl. Med. 2017 9 eaam9145 PMC9993999

[23] Ishmael M. K.,Archangeli D.,Lenzi T.. Powered hip exoskeleton improves walking economy in individuals with above-knee amputation Nat. Med. 2021 27 1783 8

[24] Lenzi T.,De Rossi S. M. M.,Vitiello N.,Carrozza M. C.. Intention-based EMG control for powered exoskeletons IEEE Trans. Biomed. Eng. 2012 59 2180 90

[25] Kim H.,Lee J.,Heo U..et al. Skin preparation-free, stretchable microneedle adhesive patches for reliable electrophysiological sensing and exoskeleton robot control Sci. Adv. 2024 10 eadk5260 PMC10793950

[26] Li J.,Wu K.,Xiao J..et al. Flexible multichannel muscle impedance sensors for collaborative human-machine interfaces Sci. Adv. 2025 11 eadv3359 PMC12204161

[27] Soekadar S. R.,Witkowski M.,Gómez C..et al. Hybrid EEG/EOG-based brain/neural hand exoskeleton restores fully independent daily living activities after quadriplegia Sci. Robot. 2016 1 eaag3296

[28] Xia H.,Zhang Y.,Rajabi N..et al. Shaping high-performance wearable robots for human motor and sensory reconstruction and enhancement Nat. Commun. 2024 15 1760 PMC10897332

[29] Ferrero L.,Soriano-segura P.,Navarro J..et al. Brain-machine interface based on deep learning to control asynchronously a lower-limb robotic exoskeleton: a case-of-study J. NeuroEng. Rehabil. 2024 21 , 48.[PMID:38581031 PMCID:PMC10996198 DOI:10.1186/s12984-024-01342-9]

[30] Chen L.,Liu Y.,Huang Y..et al. Soft bioelectronic interfaces for continuous peripheral neural signal recording and robust cross-subject decoding Adv. Sci. 2025 12 e14732 PMC12412577

[31] Tang R.,Zhang C.,Liu B..et al. Towards an artificial peripheral nerve: liquid metal-based fluidic cuff electrodes for long-term nerve stimulation and recording Biosens. Bioelectron. 2022 216 114600

[32] Dweiri Y. M.,Eggers T. E.,Gonzalez-reyes L. E.,Drain J.,Mccallum G. A.,Durand D. M.. Stable detection of movement intent from peripheral nerves: chronic study in dogs Proc. IEEE 2017 105 50 65

[33] Clements I. P.,Mukhatyar V. J.,Srinivasan A.,Bentley J. T.,Andreasen D. S.,Bellamkonda R. V.. Regenerative scaffold electrodes for peripheral nerve interfacing IEEE Trans. Neural Syst. Rehabil. Eng. 2013 21 554 66

[34] Wang L.,Zhang T.,Lei J..et al. A biodegradable and restorative peripheral neural interface for the interrogation of neuropathic injuries Nat. Commun. 2025 16 1716 PMC11832765

[35] Veith A.,Li X.,Modi H..et al. Optimized design of a hyperflexible sieve electrode to enhance neurovascular regeneration for a peripheral neural interface Biomaterials 2021 275 120924 PMC9939235

[36] Wang L.,Lu C.,Yang S..et al. A fully biodegradable and self-electrified device for neuroregenerative medicine Sci. Adv. 2020 6 eabc6686 PMC7732202

[37] Ahn H.,Walters J. B.,Avila R..et al. Bioresorbable, wireless dual stimulator for peripheral nerve regeneration Nat. Commun. 2025 16 4752 PMC12098704

[38] Layton B. E.,Sastry A. M.,Wang H.,Sullivan K. A.. A model for pressure enhancement in the diabetic nerve: Simulations of diabetic rat peripheral nerve and nerve collagens. In Annual International Conference of the IEEE Engineering in Medicine and Biology, Houston, TX, USA, October 23-26, 2002; IEEE, 2002; Vol.1, pp 450-451

[39] Walbeehm E. T.,Afoke A.,De Wit T.,Holman F.,Hovius S. E. R.,Brown R. A.. Mechanical functioning of peripheral nerves: linkage with the “mushrooming” effect Cell Tissue Res. 2004 316 115 21

[40] Borschel G. H.,Kia K. F.,Kuzon W. M.,Dennis R. G.. Mechanical properties of acellular peripheral nerve J. Surg. Res. 2003 114 133 9

[41] Yu B.,Bai J.,Guan Y..et al. Fully biodegradable and self-powered nerve guidance conduit based on zinc-molybdenum batteries for peripheral nerve repair Biosens. Bioelectron. 2024 263 116578

[42] Xue N.,Martinez I. D.,Sun J.,Cheng Y.,Liu C.. Flexible multichannel vagus nerve electrode for stimulation and recording for heart failure treatment Biosens. Bioelectron. 2018 112 114 9

[43] Kim D.,Bissannagari M.,Kim B..et al. Hexagonal metal complex based mechanically robust transparent ultrathin gold µECoG for electro-optical neural interfaces npj Flex. Electron. 2025 9 31

[44] Zhang Y.,Zheng N.,Cao Y..et al. Climbing-inspired twining electrodes using shape memory for peripheral nerve stimulation and recording Sci. Adv. 2019 5 eaaw1066 PMC6505533

[45] Watling K.,Hope G. A.,Woods R.. SERS investigation of gold dissolution in chloride and cyanide media J. Electrochem. Soc. 2005 152 D103

[46] Laycock B.,Nikolić M.,Colwell J. M..et al. Lifetime prediction of biodegradable polymers Prog. Polym. Sci. 2017 71 144 89

[47] Choi Y. S.,Koo J.,Lee Y. J..et al. Biodegradable polyanhydrides as encapsulation layers for transient electronics Adv. Funct. Mater. 2020 30 2000941

[48] Makino K.,Arakawa M.,Kondo T.. Preparation and in vitro degradation properties of polylactide microcapsules Chem. Pharm. Bull. 1985 33 1195 201

[49] Ye W. P.,Du F. S.,Jin W. H.,Yang J. Y.,Xu Y.. In vitro degradation of poly(caprolactone), poly(lactide) and their block copolymers: influence of composition, temperature and morphology React. Funct. Polym. 1997 32 161 8

[50] Won C.,Jeong U. J.,Lee S..et al. Mechanically tissue-like and highly conductive Au nanoparticles embedded elastomeric fiber electrodes of brain-machine interfaces for chronic in vivo brain neural recording Adv. Funct. Mater. 2022 32 2205145

[51] Hiendlmeier L.,Zurita F.,Vogel J..et al. 4D-printed soft and stretchable self-folding cuff electrodes for small-nerve interfacing Adv. Mater. 2023 35 2210206

[52] Gosens I.,Post J. A.,De La Fonteyne L. J..et al. Impact of agglomeration state of nano- and submicron sized gold particles on pulmonary inflammation Part. Fibre Toxicol. 2010 7 37 PMC3014867

[53] Larsen A.,Kolind K.,Pedersen D. S..et al. Gold ions bio-released from metallic gold particles reduce inflammation and apoptosis and increase the regenerative responses in focal brain injury Histochem. Cell Biol. 2008 130 681 92

[54] Danscher G.. In vivo liberation of gold ions from gold implants. Autometallographic tracing of gold in cells adjacent to metallic gold Histochem. Cell Biol. 2002 117 447 52

[55] Gaudet A. D.,Popovich P. G.,Ramer M. S.. Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury J. Neuroinflammation 2011 8 110 PMC3180276

[56] Van Den Brand R.,Heutschi J.,Barraud Q..et al. Restoring voluntary control of locomotion after paralyzing spinal cord injury Science 2012 336 1182 5

[57] Bonizzato M.,Pidpruzhnykova G.,Digiovanna J..et al. Brain-controlled modulation of spinal circuits improves recovery from spinal cord injury Nat. Commun. 2018 9 3015 PMC6070513

[58] Yang S.,Wang C.,Zhu J..et al. Self-assembling peptide hydrogels functionalized with LN- and BDNF- mimicking epitopes synergistically enhance peripheral nerve regeneration Theranostics 2020 10 8227 49 PMC7381722

[59] Yang S.,Zhu J.,Lu C..et al. Aligned fibrin/functionalized self-assembling peptide interpenetrating nanofiber hydrogel presenting multi-cues promotes peripheral nerve functional recovery Bioact. Mater. 2022 8 529 44 PMC8435993

[60] Young D.,Willett F.,Memberg W. D..et al. Signal processing methods for reducing artifacts in microelectrode brain recordings caused by functional electrical stimulation J. Neural Eng. 2018 15 026014 PMC5818316

[61] Duan X. H.,Cheng L.. Na; Zhang, F.; et al. In vivo MRI monitoring nerve regeneration of acute peripheral nerve traction injury following mesenchymal stem cell transplantation Eur. J. Radiol. 2012 81 2154 60

[62] Ricci V.,Ricci C.,Cocco G..et al. Histopathology and high-resolution ultrasound imaging for peripheral nerve (injuries) J. Neurol. 2022 269 3663 75

[63] Jin S.,Choi H.,Son D.,Shin M.. An injectable conductive hydrogel for closed-loop and robot-assisted rehabilitation via stretchable patch-type electrodes Nat. Protoc. 2025 21 238 62

[64] Farrell T. R.,Weir R. F.. The optimal controller delay for myoelectric prostheses IEEE Trans. Neural Syst. Rehabil. Eng. 2007 15 111 8 PMC8173529

[65] Heo U.,Feng J.,Kim S. J.,Kim J.. sEMG-triggered fast assistance strategy for a pneumatic back support exoskeleton IEEE Trans. Neural Syst. Rehabil. Eng. 2022 30 2175 85

[66] Jia Y.,Ye X.,Zhou X.,Ling Y.,Rus D.,Yeow C. H.. Myoelectric origami-based soft robotic knee exoskeleton to enhance sit-to-stand assistance in elderly populations Adv. Intell. Syst. 2025 8 e202501036

[67] Paggi V.,Akouissi O.,Micera S.,Lacour S. P.. Compliant peripheral nerve interfaces J. Neural Eng. 2021 18 031001

[68] Schiavone G.,Kang X.,Fallegger F.,Gandar J.,Courtine G.,Lacour S. P.. Guidelines to study and develop soft electrode systems for neural stimulation Neuron 2020 108 238 58

[69] Liu Y.,Li J.,Song S..et al. Morphing electronics enable neuromodulation in growing tissue Nat. Biotechnol. 2020 38 1031 6 PMC7805559

[70] Wach R. A.,Adamus A.,Kowalska-ludwicka K..et al. Experimental research in vivo evaluation of nerve guidance channels of PTMC/PLLA porous biomaterial Arch. Med. Sci. 2015 1 210 9 PMC4379356

[71] ECRI. Polycaprolactone (PCL) Safety Profile. 2021. https://www.fda.gov/media/158492/download (accessed 2026-06-08)

[72] Liang J.,Wang X.,Chen Z..et al. Silk-enabled conformal intraventricular interfaces for minimally invasive neural recordings Nat. Commun. 2025 16 9366 PMC12549829

[73] Li W.,Li X.,Yang M..et al. Robust neural interfaces enabled by non-deformable adhesive hydrogel patch for stable chronic ECoG recording Adv. Funct. Mater. 2025 35 2422717

[74] Carnicer-lombarte A.,Boys A. J.,Güemes A..et al. Ultraconformable cuff implants for long-term bidirectional interfacing of peripheral nerves at sub-nerve resolutions Nat. Commun. 2024 15 7523 PMC11364531

[75] Lewitus D.,Vogelstein R. J.,Zhen G..et al. Designing tyrosine-derived polycarbonate polymers for biodegradable regenerative type neural interface capable of neural recording IEEE Trans. Neural Syst. Rehabil. Eng. 2011 19 204 12

[76] Lee D.,Kang M.,Hyun I..et al. An on-demand bioresorbable neurostimulator Nat. Commun. 2023 14 7315 PMC10640647

[77] Lee G.,Ray E.,Yoon H..et al. A bioresorbable peripheral nerve stimulator for electronic pain block Sci. Adv. 2022 8 eabp9169 PMC9534494

[78] Fadia N. B.,Bliley J. M.,Dibernardo G. A..et al. Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates Sci. Transl. Med. 2020 12 eaav7753

[79] Liu P.,Zhou L.,Xu D..et al. A self-wrapping, bioresorbable neural interface for wireless multimodal therapy of localized peripheral nerve injury Proc. Natl. Acad. Sci. U.S.A. 2026 123 e2521817123

[80] Choi H.,Kim S.,Kim S..et al. Brain-adhesive bioelectronics with shape-morphable and biodegradable properties for stable brain signal monitoring Adv. Sci. 2026 13 e18255 PMC13116226