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Probabilistic cell seeding and non-autofluorescent 3D-printed structures as scalable approach for multi-level co-culture modeling
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.ORCID iD: 0000-0001-7442-3020
KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.ORCID iD: 0000-0002-8821-6759
KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.ORCID iD: 0000-0002-7580-3049
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.ORCID iD: 0000-0002-0999-6671
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2023 (English)In: Materials Today Bio, ISSN 2590-0064, Vol. 21, p. 100706-100706, article id 100706Article in journal (Refereed) Published
Abstract [en]

To model complex biological tissue in vitro, a specific layout for the position and numbers of each cell type isnecessary. Establishing such a layout requires manual cell placement in three dimensions (3D) with micrometricprecision, which is complicated and time-consuming. Moreover, 3D printed materials used in compartmentalizedmicrofluidic models are opaque or autofluorescent, hindering parallel optical readout and forcing serial charac-terization methods, such as patch-clamp probing. To address these limitations, we introduce a multi-level co-culture model realized using a parallel cell seeding strategy of human neurons and astrocytes on 3D structuresprinted with a commercially available non-autofluorescent resin at micrometer resolution. Using a two-stepstrategy based on probabilistic cell seeding, we demonstrate a human neuronal monoculture that forms net-works on the 3D printed structure and can establish cell-projection contacts with an astrocytic-neuronal co-cultureseeded on the glass substrate. The transparent and non-autofluorescent printed platform allows fluorescence-based immunocytochemistry and calcium imaging. This approach provides facile multi-level compartmentaliza-tion of different cell types and routes for pre-designed cell projection contacts, instrumental in studying complextissue, such as the human brain.

Place, publisher, year, edition, pages
Elsevier BV , 2023. Vol. 21, p. 100706-100706, article id 100706
Keywords [en]
Two-photon polymerization Neurons Astrocytes Calcium imaging Co-culture models IP-Visio
National Category
Nano Technology Bio Materials Cell Biology
Identifiers
URN: urn:nbn:se:kth:diva-331732DOI: 10.1016/j.mtbio.2023.100706ISI: 001030630300001PubMedID: 37435551Scopus ID: 2-s2.0-85166735644OAI: oai:DiVA.org:kth-331732DiVA, id: diva2:1782483
Note

Correction in Materials Today Bio, vol. 23. DOI:10.1016/j.mtbio.2023.100892

QC 20231221

Available from: 2023-07-14 Created: 2023-07-14 Last updated: 2024-02-06Bibliographically approved
In thesis
1. Organic Electronics and Microphysiological Systems to Interface, Monitor, and Model Biology
Open this publication in new window or tab >>Organic Electronics and Microphysiological Systems to Interface, Monitor, and Model Biology
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Biological processes in the human body are regulated through complex and precise arrangements of cell structures and their interactions. In vivo models serve as the most accurate choice for biological studies to understand these processes. However, they are costly, time-consuming, and raise ethical issues. Microphysiological systems have been developed to create advanced in vitro models that mimic in vivo-like microenvironments. They are often combined with integrated sensing technologies to perform real-time measurements to gain additional information. However, conventional sensing electrodes, made of inorganic materials such as gold or platinum, differ fundamentally from biological materials. Organic bioelectronic devices made from conjugated polymers are promising alternatives for biological sensing applications and aim to improve the interconnection between abiotic electronics and biotic materials. The widespread use of these devices is partly hindered by the limited availability of materials and low-cost fabrication methods. In this thesis, we provide new tools and materials that facilitate the use of organic bioelectronic devices for in vitro sensing applications. We developed a method to pattern the conducting polymer poly(3,4‑ethylenedioxythiophene) polystyrene sulfonate and to fabricate organic microelectronic devices using wax printing, filtering, and tape transfer. The method is low-cost, time-effective, and compatible with in vitro cell culture models. To achieve higher resolution, we further developed a patterning method using femtosecond laser ablation to fabricate organic electronic devices such as complementary inverters or biosensors. The method is maskless and independent of the type of conjugated polymer. Besides fabrication processes, we introduced a newly synthesized material, the semiconducting conjugated polymer p(g42T‑T)‑8%OH. This polymer contains hydroxylated side chains that enable surface modifications, allowing control of cell adhesion. Using the new femtosecond laser-based patterning method, we could fabricate p(g42T‑T)‑8%OH‑based organic electrochemical transistors to monitor cell barrier formations in vitro. Microphysological systems are further dependent on precise compartmentalization to study cellular interaction. We used femtosecond laser 3D printing to develop a co-culture neurite guidance platform to control placement and interactions between different types of brain cells. In summary, the thesis provides new tools to facilitate the fabrication of organic electronic devices and microphysiological systems. This increases their accessibility and widespread use to interface, monitor, and model biological systems. 

Abstract [sv]

Biologiska processer i människokroppen regleras genom komplexa och exakta arrangemang av cellstrukturer och deras interaktioner. In vivo modeller är det mest exakta valet för biologiska studier för att förstå dessa processer. Men de är dyra, tidskrävande och behäftade med etiska dilemman. Mikrofysiologiska system har utvecklats för att skapa avancerade in vitro-modeller för att efterlikna mikromiljöer som finns in vivo. Dessa system kombineras ofta med integrerade sensortekniker för att utföra mätningar i realtid för att få ytterligare information. Konventionella elektroder, gjorda av oorganiska material som guld eller platina, skiljer sig dock fundamentalt från biologiska material. Organiska bioelektroniska komponenter tillverkade av konjugerade polymerer är intressanta alternativ för biologiska sensortillämpningar eftersom de har potential att förbättra sammankopplingen mellan abiotisk elektronik och biotiska material. Deras användning hindras delvis av den begränsade tillgången på material och billiga tillverkningsmetoder. I den här avhandlingen tillhandahåller vi nya verktyg och material som underlättar användningen av organiska bioelektroniska komponenter för in vitro avkänningstillämpningar. Vi utvecklade en metod för att mönstra den ledande polymeren poly(3,4-etylendioxitiofen) polystyrensulfonat och tillverka organiska mikroelektroniska komponenter med hjälp av vaxtryck, filtrering och tejpöverföring. Metoden har låg kostnad, är tidseffektiv och kompatibel med in vitro cellodlingsmodeller. För att uppnå högre upplösning vidareutvecklade vi en mönstringsmetod med femtosekundlaserablation för att tillverka organiska elektroniska enheter såsom komplementära växelriktare eller biosensorer. Metoden involverar inga masker och är inte beroende av typen av konjugerad polymer. Förutom tillverkningsprocesser introducerade vi ett nytt material, den konjugerade polymeren p(g42T‑T)‑8%OH. Denna polymer innehåller hydroxylerade sidokedjor som möjliggör ytmodifieringar, vilket tillåter kontroll av celladhesion. Med den nya femtonsekundslaser baserade mönstringsmetoden kunde vi tillverka p(g42T‑T)‑8%OH-baserade organiska elektrokemiska transistorer för att följa cellbarriärformationer in vitro. Slutligen använde vi femtonsekundslaserutskrift för att tillverka en plattform som kan guida neuriter i co-kultur  för att undersöka cellinteraktionerna mellan olika typer av hjärnceller. Sammanfattningsvis beskriver avhandlingen nya verktyg för att underlätta tillverkningen av organiska elektroniska enheter och mikrofysiologiska system. Detta ökar deras tillgänglighet och möjliggör utbredd användning för gränssnitt, övervakning och modellering av biologiska system.

Place, publisher, year, edition, pages
Stockholm: Kungliga Tekniska högskolan, 2024. p. 69
Series
TRITA-CBH-FOU ; 2024:3
Keywords
organic bioelectronics, organic electrochemical transistors, conjugated polymers, microphysiological systems, in vitro cell models, Organisk bioelektronik, organiska elektrokemiska transistorer, Konjugerade polymerer, Mikrofysiologiska system, in vitro-modeller
National Category
Cell Biology Organic Chemistry Engineering and Technology Electrical Engineering, Electronic Engineering, Information Engineering
Research subject
Medical Technology
Identifiers
urn:nbn:se:kth:diva-343016 (URN)978-91-8040-837-0 (ISBN)
Public defence
2024-03-05, Nils Ringertz, Biomedicum, Solnavägen 9, 17165, Solna, 09:00 (English)
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Supervisors
Note

QC 2024-02-06

Available from: 2024-02-06 Created: 2024-02-06 Last updated: 2024-04-05Bibliographically approved

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Buchmann, SebastianEnrico, AlessandroHolzreuter, Muriel AlexandraReid, Michael S.Zeglio, EricaNiklaus, FrankStemme, GöranHerland, Anna

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