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Materials and Devices for Stretchable Electronic Nerve Interfaces
Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0001-9818-1687
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Within our body, there is a large network of nerves that facilitates communication between the brain and the body’s organs. This network is called our peripheral nervous system, consisting of soft and stretchable nerve bundles that gradually increase in their functional specificity as they split and branch out the closer they get to their target organ. Communication within the nerve is based on action potentials, fast fluctuations in electric trans-membrane potential along the neurons within the nerve. These action potentials can be recorded and artificially triggered by interfacing electronically with peripheral nerves. In doing so, modern medicine is able to elucidate the mechanisms behind disorders related to the nervous system and even applies novel electronic therapies to treat them. Over the last decade, the field of biomedical engineering has therefore seen a surge of interest in electronic devices that interface with the peripheral nervous system, such as cuff electrodes. The device function is based on electrodes that are implanted in close proximity of the nerves they intend to record or stimulate. A cuff electrode, specifically, is wrapped around a peripheral nerve and applies stimulation pulses at electrodes located on the inside of the cuff to evoke action potentials within the nerve. 

Our body is not welcoming to foreign objects though. Any implant within our body triggers a foreign body reaction with an intensity dependent on the biocompatibility of the implant. Recent studies have found that one of the major factors governing the foreign body reaction is the mechanical mismatch of the implant to the interfacing tissue, with softer, more mechanically similar implants, exhibiting reduced foreign body response. This has prompted an ongoing push for thin and soft peripheral nerve interfaces. However, to truly match the mechanical properties of peripheral nerves, peripheral nerve interfaces need not only to be soft and flexible, they need to become as elastic and stretchable as the nerve themselves. 

A common strategy to achieve stretchable conductors is by incorporating highly conductive filler materials in an elastomeric matrix. The resulting composite remains conductive even when stretched due to the ability of the filler material to dislocate with the elastomeric matrix while retaining its interconnectivity and thus conductivity. Electronic composites based on gold nanowires and silicones are promising candidates for stretchable peripheral nerve interfaces, due to their material-based biocompatibility, good stretchability, and versatile patterning possibilities.

Based on this, the thesis at hand investigated stretchable electronic composite materials and devices to interface with the peripheral nervous system. Publication I and II develop gold-nanowire/polydimethylsiloxane-based cuff electrodes, which are functional even at 50% strain, as peripheral nerve interfaces in vivo. These publications highlight the beneficial conformability of stretchable devices, with a stretchable bi-polar cuff for low-voltage stimulation of the rat sciatic nerve in publication I and a stretchable multi-electrode cuff for selective stimulation of the pig sciatic nerve in publication II. Publication III investigates stretchable gold-nanowire composites based on a variety of elastomers, therein, elucidating the influence of the varying elastomer properties on the electromechanical performance of gold-nanowire composites. Lastly, publication IV establishes a stretchable ion delivery device with potential use for the peripheral nervous system. The device is based on an ionically conductive membrane as the conductive filler, and the device can be reversibly stretched to 100% strain. Overall, this thesis presents stretchable materials and devices that advance the possibilities for peripheral nerve interfaces.

Abstract [sv]

Vår kropp innehåller ett stort nätverk av nerver som förmedlar kommunikationen mellan hjärnan och kroppens organ. Detta system kallas det perifera nerv-systemet och består av mjuka och töjbara nervknippen som gradvis förmedlar en mer specifik funktionalitet då nerverna förgrenar sig till organen ute i kroppen som de ansluter till. Kommunikationen inom nerver är baserad på snabba fluktuationer i membranpotential längs med nervcellerna, så kallade aktionspotentialer. Med elektroniska nervgränssnitt kan dessa aktionspotentialer läsas ut eller induceras artificiellt. Detta ger möjligheter till att diagnosticera störningar i nervsystemet och med hjälp av nydanande elektrisk terapi behandla dem. Under det senaste årtiondet har därför intresset för perifera nervgränssnitt ökat inom biomedicinsk teknik. Nervgränssnittens funktion bygger på att elektroder implanteras i nära anslutning till de nerver som de ämnar läsa ut signaler ifrån eller stimulera. Ett av de vanligaste nervgränssnitten är så kallade cuff-elektroder, som viras runt nerven och stimulerar den genom att skicka elektriska pulser genom elektroder lokaliserade på insidan gentemot nerven. En utmaning är att kroppen regerar på alla främmande objekt, där styrkan i reaktionen beror på objektets biokompatibilitet. På senare tid har flera studier påvisat att skillnader i mekaniska egenskaper mellan vävnad och implantat kan ha stor påverkan på kroppens svar mot främmande objekt. Mjuka implantat som matchar nervers mekaniska egenskaper kan därför minska kroppssvaret och detta har skapat ett intresse för att utveckla tunna och mjuka nervgränssnitt. För att matcha en nervs mekaniska egenskaper räcker det dock inte att gränssnittet är tunt och flexibelt, det behöver också vara töjbart.

En vanlig strategi för att åstadkomma töjbara elektriska ledare är att skapa kompositmaterial bestående av ledande partiklar och elastomergummi. Ledningsförmågan i sådana kompositer kan bevaras även vid omfattande töjning då partiklarna kan röra sig i kompositen och på så sätt bevara det ledande nätverket. Töj-bar elektronik baserade på guldnanotrådar och silikongummi är en lovande kandidat för framtidens töjbara nervgränssnitt då materialen är biokompatibla, hög-presterande under töjning, och mönstringsbara med flera olika metoder. Denna avhandling utforskar sådana töjbara elektroniska material och komponenter för skapandet av elektriska gränssnitt för det perifera nervsystemet. I artikel I och II så utvecklas cuff-elektroder baserade på guldnanotrådar och silikongummi. Elektroderna är fullt funktionella vid 50% töjning och dess funktion verifieras in vivo. Artiklarna påvisar fördelarna med konformerbara elektroder genom att i artikel I åstadkomma nervstimulering med extremt låga spänningar av ischiasnerven i råttor och i artikel II uppnå selektiv stimulering av ischiasnerven i grisar med en flerelektrod-cuff. I artikel III studeras egenskaperna hos kompositer av guldnanotrådar och ett flertal olika elastomergummin. Studien visar på hur olika egenskaper av elastomeren avgör den elektriska prestandan för kompositer vid töjning. En alternativ teknik för att stimulera nerver utvecklas i artikel IV i form av ett töjbart jonleveranssystem som fungerar upp till 100% töjning.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2022. , p. 91
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 2236
Keywords [en]
Stretchable electronics, Nanowires, Peripheral nerve interfaces, Cuff electrodes
National Category
Medical Laboratory Technologies
Identifiers
URN: urn:nbn:se:liu:diva-187243DOI: 10.3384/9789179293666ISBN: 9789179293659 (print)ISBN: 9789179293666 (electronic)OAI: oai:DiVA.org:liu-187243DiVA, id: diva2:1687547
Public defence
2022-09-09, K1, Kåkenhus, Campus Norrköping, Norrköping, 13:00 (English)
Opponent
Supervisors
Available from: 2022-08-16 Created: 2022-08-16 Last updated: 2025-02-09Bibliographically approved
List of papers
1. Stretchable gold nanowire-based cuff electrodes for low-voltage peripheral nerve stimulation
Open this publication in new window or tab >>Stretchable gold nanowire-based cuff electrodes for low-voltage peripheral nerve stimulation
2021 (English)In: Journal of Neural Engineering, ISSN 1741-2560, E-ISSN 1741-2552, Vol. 18, no 4, article id 045007Article in journal (Refereed) Published
Abstract [en]

Objective. Electrical stimulation of the peripheral nervous system (PNS) can treat various diseases and disorders, including the healing process after nerve injury. A major challenge when designing electrodes for PNS stimulation is the mechanical mismatch between the nerve and the device, which can lead to non-conformal contact, tissue damage and inefficient stimulation due to current leakage. Soft and stretchable cuff electrodes promise to tackle these challenges but often have limited performance and rely on unconventional materials. The aim of this study is to develop a high performance soft and stretchable cuff electrode based on inert materials for low-voltage nerve stimulation. Approach. We developed 50 mu m thick stretchable cuff electrodes based on silicone rubber, gold nanowire conductors and platinum coated nanowire electrodes. The electrode performance was characterized under strain cycling to assess the durability of the electrodes. The stimulation capability of the cuff electrodes was evaluated in an in vivo sciatic nerve rat model by measuring the electromyography response to various stimulation pulses. Main results. The stretchable cuff electrodes showed excellent stability for 50% strain cycling and one million stimulation pulses. Saturated homogeneous stimulation of the sciatic nerve was achieved at only 200 mV due to the excellent conformability of the electrodes, the low conductor resistance (0.3 Ohm sq(-1)), and the low electrode impedance. Significance. The developed stretchable cuff electrode combines favourable mechanical properties and good electrode performance with inert and stable materials, making it ideal for low power supply applications within bioelectronic medicine.

Place, publisher, year, edition, pages
IOP PUBLISHING LTD, 2021
Keywords
cuff electrodes; electrical stimulation; stretchable electronics; neural interfaces; bioelectronics; gold nanowires; peripheral nervous system
National Category
Other Medical Engineering
Identifiers
urn:nbn:se:liu:diva-176129 (URN)10.1088/1741-2552/abfebb (DOI)000655282100001 ()33957608 (PubMedID)
Note

Funding Agencies|Swedish Foundation for Strategic Research, Swedens Innovation Agency (VINNOVA); Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO Mat LiU) [2009 00971]

Available from: 2021-06-08 Created: 2021-06-08 Last updated: 2024-01-10
2. Soft iontronic delivery devices based on an intrinsically stretchable ion selective membrane
Open this publication in new window or tab >>Soft iontronic delivery devices based on an intrinsically stretchable ion selective membrane
Show others...
2021 (English)In: Flexible and Printed Electronics, ISSN 2058-8585, Vol. 6, no 4, article id 044004Article in journal (Refereed) Published
Abstract [en]

Implantable electronically controlled drug delivery devices can provide precision therapeutic treatments by highly spatiotemporally controlled delivery. Iontronic delivery devices rely on the movement of ions rather than liquid, and can therefore achieve electronically controlled precision delivery in a compact setting without disturbing the microenvironment within the tissue with fluid flow. For maximum precision, the delivery device needs to be closely integrated into the tissue, which is challenging due to the mechanical mismatch between the soft tissue and the harder devices. Here we address this challenge by developing a soft and stretchable iontronic delivery device. By formulating an ink based on an in-house synthesized hyperbranched polyelectrolyte, water dispersed polyurethane, and a thickening agent, a viscous ink is developed for stencil patterning of soft ion exchange membranes (IEMs). We use this ink for developing soft and stretchable delivery devices, which are characterized both in the relaxed and stretched state. We find that their functionality is preserved up to 100% strain, with small variations in resistance due to the strain. Finally, we develop a skin patch to demonstrate the outstanding conformability of the developed device. The presented technology is attractive for future soft implantable delivery devices, and the stretchable IEMs may also find applications within wearable energy devices.

Place, publisher, year, edition, pages
IOP Publishing Ltd, 2021
Keywords
iontronics; stretchable electronics; drug delivery; ion pumps; bioelectronics
National Category
Medical Instrumentation
Identifiers
urn:nbn:se:liu:diva-182380 (URN)10.1088/2058-8585/ac356e (DOI)000739541000001 ()
Note

Funding Agencies|Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; Swedish Government Strategic Research Area in Materials Science on Advanced Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [2009-00971]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2019-04424, 2020-05218]

Available from: 2022-01-19 Created: 2022-01-19 Last updated: 2025-02-10

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Lienemann, Samuel Lukas

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