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Biocompatibility of PEDOT/biomolecular composites intended for neural communication electrodes
KTH, Skolan för teknik och hälsa (STH), Neuronik. (Neuronik)
KTH, Skolan för teknik och hälsa (STH), Neuronik. (Neuronik)
Visa övriga samt affilieringar
(Engelska)Manuskript (Övrig (populärvetenskap, debatt, mm))
Abstract [en]

Electrodes of the conjugated polymer poly(3,4-ethylene dioxythiophene) (PEDOT) have been shown to possess very attractive electrochemical properties for functional electrical stimulation (FES) or recording in the nervous system. Biomolecules already present in nervous tissue, added as counter ions in PEDOT electropolymerisation, could be a route to further improve the biomaterial properties of PEDOT, eliminating the need of surfactant counter ions like docedyl benzene sulphonate (DBS) or polystyrene sulphonate (PSS) in the polymerisation process. Such PEDOT/biomolecular composites using heparin, or hyaluronic acid, have been electrochemically investigated in a previous study and have been shown to retain the attractive electrochemical properties already proven for PEDOT:PSS.

 

The aim of the present study is to evaluate biocompatibility of these PEDOT/biomolecular composites in vitro and also evaluate PEDOT:heparin biocompatibility in cortical tissue in vivo. Hereby, we also aim to identify a suitable test protocol, that can be used in future evaluations when further material developments are made.

 

Material toxicity was first tested on cell lines, both through a standardised agarose overlay assay on L929 fibroblasts, and through elution tests on human neuroblastoma SH-SY5Y cells. Subsequently, a biocompatibility in vivo test was performed using PEDOT:heparin coated platinum probes implanted in the cerebral cortex of Sprague-Dawley rats. Tissue was collected at three weeks and six weeks of implantation and evaluated by immunohistochemistry.

 

No cytotoxic response was seen to any of the PEDOT:biomolecular composites tested here. Furthermore, elution tests were found to be a practical and effective way of screening materials for toxicity and had a clear advantage over the agarose overlay assay, which was difficult to apply on other cell types than fibroblasts. Elution tests would therefore be recommendable as a screening method, at all stages of material development. In the in vivo tests, the stiffness of the platinum substrate was a significant problem, and extensive glial scarring was seen in most cases irrespective of implant material. However, quantification of immunological response through distance measurements from implant site to closest neuron, and counting of macrophage densities in proximity to polymer surface, was comparable to those of platinum controls. These results indicate that PEDOT:heparin surfaces were as compatible with cortical tissue as pure platinum controls.

Nyckelord [en]
biocompatibility, conducting polymers, PEDOT, neuroprosthetics
Nationell ämneskategori
Övrig annan teknik
Identifikatorer
URN: urn:nbn:se:kth:diva-9845OAI: oai:DiVA.org:kth-9845DiVA, id: diva2:133566
Anmärkning
QC 20100623Tillgänglig från: 2009-01-12 Skapad: 2009-01-12 Senast uppdaterad: 2022-06-26Bibliografiskt granskad
Ingår i avhandling
1. Conjugated Polymers for Neural Interfaces: Prospects, possibilities and future challenges
Öppna denna publikation i ny flik eller fönster >>Conjugated Polymers for Neural Interfaces: Prospects, possibilities and future challenges
2009 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Within the field of neuroprosthetics the possibility to use implanted electrodes for communication with the nervous system is explored. Much effort is put into the material aspects of the electrode implant to increase charge injection capacity, suppress foreign body response and build micro sized electrode arrays allowing close contact with neurons. Conducting polymers, in particular poly(3,4-ethylene dioxythiophene) (PEDOT), have been suggested as materials highly interesting for such neural communication electrodes. The possibility to tailor the material both mechanically and biochemically to suit specific applications, is a substantial benefit with polymers when compared to metals. PEDOT also have hybrid charge transfer properties, including both electronic and ionic conduction, which allow for highly efficient charge injection.

 

Part of this thesis describes a method of tailoring PEDOT through exchanging the counter ion used in electropolymerisation process. Commonly used surfactants can thereby be excluded and instead, different biomolecules can be incorporated into the polymer. The electrochemical characteristics of the polymer film depend on the ion. PEDOT electropolymerised with heparin was here determined to have the most advantageous properties. In vitro methods were applied to confirm non-cytotoxicity of the formed PEDOT:biomolecular composites. In addition, biocompatibility was affirmed for PEDOT:heparin by evaluation of inflammatory response and neuron density when implanted in rodent cortex.

 

One advantage with PEDOT often stated, is its high stability compared to other conducting polymers. A battery of tests simulating the biological environment was therefore applied to investigate this stability, and especially the influence of the incorporated heparin. These tests showed that there was a decline in the electroactivity of PEDOT over time. This also applied in phosphate buffered saline at body temperature and in the absence of other stressors. The time course of degradation also differed depending on whether the counter ion was the surfactant polystyrene sulphonate or heparin, with a slightly better stability for the former.

 

One possibility with PEDOT, often overlooked for biological applications, is the use of its semi conducting properties in order to include logic functions in the implant. This thesis presents the concept of using PEDOT electrochemical transistors to construct textile electrode arrays with in-built multiplexing. Using the electrolyte mediated interaction between adjacent PEDOT coated fibres to switch the polymer coat between conducting and non conducting states, then transistor function can be included in the conducting textile. Analogue circuit simulations based on experimentally found transistor characteristics proved the feasibility of these textile arrays. Developments of better polymer coatings, electrolytes and encapsulation techniques for this technology, were also identified to be essential steps in order to make these devices truly useful.

 

In summary, this work shows the potential of PEDOT to improve neural interfaces in several ways. Some weaknesses of the polymer and the polymer electronics are presented and this, together with the epidemiological data, should point in the direction for future studies within this field.

Ort, förlag, år, upplaga, sidor
Stockholm: KTH, 2009. s. vi, 77
Serie
Trita-STH : report, ISSN 1653-3836 ; 2009:1
Nyckelord
neuroprosthetics, conjugated polymers, conducting polymers, PEDOT, functional electrical stimulation, neural electrodes
Nationell ämneskategori
Medicinsk laboratorie- och mätteknik Neurovetenskaper Annan materialteknik
Identifikatorer
urn:nbn:se:kth:diva-9817 (URN)978-91-7415-213-5 (ISBN)
Disputation
2009-01-30, Sal 3-221, Alfred Nobels Allé 10, Huddinge, 13:00 (Engelska)
Opponent
Handledare
Anmärkning
QC 20100623Tillgänglig från: 2009-01-13 Skapad: 2009-01-09 Senast uppdaterad: 2022-06-26Bibliografiskt granskad

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Asplund, MariaThaning, Elinvon Holst, Hans
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