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Enrico, A., Buchmann, S., De Ferrari, F., Lin, Y., Wang, Y., Yue, W., . . . Zeglio, E. (2024). Cleanroom‐Free Direct Laser Micropatterning of Polymers for Organic Electrochemical Transistors in Logic Circuits and Glucose Biosensors. Advanced Science
Open this publication in new window or tab >>Cleanroom‐Free Direct Laser Micropatterning of Polymers for Organic Electrochemical Transistors in Logic Circuits and Glucose Biosensors
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2024 (English)In: Advanced Science, E-ISSN 2198-3844Article in journal (Refereed) Published
Abstract [en]

Organic electrochemical transistors (OECTs) are promising devices for bioelectronics, such as biosensors. However, current cleanroom-based microfabrication of OECTs hinders fast prototyping and widespread adoption of this technology for low-volume, low-cost applications. To address this limitation, a versatile and scalable approach for ultrafast laser microfabrication of OECTs is herein reported, where a femtosecond laser to pattern insulating polymers (such as parylene C or polyimide) is first used, exposing the underlying metal electrodes serving as transistor terminals (source, drain, or gate). After the first patterning step, conducting polymers, such as poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), or semiconducting polymers, are spin-coated on the device surface. Another femtosecond laser patterning step subsequently defines the active polymer area contributing to the OECT performance by disconnecting the channel and gate from the surrounding spin-coated film. The effective OECT width can be defined with high resolution (down to 2 µm) in less than a second of exposure. Micropatterning the OECT channel area significantly improved the transistor switching performance in the case of PEDOT:PSS-based transistors, speeding up the devices by two orders of magnitude. The utility of this OECT manufacturing approach is demonstrated by fabricating complementary logic (inverters) and glucose biosensors, thereby showing its potential to accelerate OECT research.

Place, publisher, year, edition, pages
Wiley, 2024
Keywords
conjugated polymer, direct writing, organic electrochemical transistor, poly(3, 4-ethylenedioxythiophene) polystyrene sulfonate, ultrashort pulsed lasers
National Category
Organic Chemistry Other Electrical Engineering, Electronic Engineering, Information Engineering Other Materials Engineering
Identifiers
urn:nbn:se:kth:diva-342521 (URN)10.1002/advs.202307042 (DOI)001142422700001 ()2-s2.0-85182492139 (Scopus ID)
Funder
Swedish Research Council, 2018‐03483Swedish Research Council, 2022‐04060Swedish Research Council, 2022‐02855Knut and Alice Wallenberg Foundation, 2015.0178Knut and Alice Wallenberg Foundation, 2020.0206Knut and Alice Wallenberg Foundation, 2021.0312Swedish Research Council, 2022-00374
Note

QC 20240123

Available from: 2024-01-23 Created: 2024-01-23 Last updated: 2024-02-06Bibliographically approved
Reyes, D. R., Esch, M. B., Ewart, L., Nasiri, R., Herland, A., Sung, K., . . . Ashammakhi, N. (2024). From animal testing to in vitro systems: advancing standardization in microphysiological systems. Lab on a Chip, 24(5), 1076-1087
Open this publication in new window or tab >>From animal testing to in vitro systems: advancing standardization in microphysiological systems
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2024 (English)In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 24, no 5, p. 1076-1087Article, review/survey (Refereed) Published
Abstract [en]

Limitations with cell cultures and experimental animal-based studies have had the scientific and industrial communities searching for new approaches that can provide reliable human models for applications such as drug development, toxicological assessment, and in vitro pre-clinical evaluation. This has resulted in the development of microfluidic-based cultures that may better represent organs and organ systems in vivo than conventional monolayer cell cultures. Although there is considerable interest from industry and regulatory bodies in this technology, several challenges need to be addressed for it to reach its full potential. Among those is a lack of guidelines and standards. Therefore, a multidisciplinary team of stakeholders was formed, with members from the US Food and Drug Administration (FDA), the National Institute of Standards and Technology (NIST), European Union, academia, and industry, to provide a framework for future development of guidelines/standards governing engineering concepts of organ-on-a-chip models. The result of this work is presented here for interested parties, stakeholders, and other standards development organizations (SDOs) to foster further discussion and enhance the impact and benefits of these efforts.

Place, publisher, year, edition, pages
Royal Society of Chemistry (RSC), 2024
National Category
Basic Medicine
Identifiers
urn:nbn:se:kth:diva-344375 (URN)10.1039/d3lc00994g (DOI)38372151 (PubMedID)2-s2.0-85186268810 (Scopus ID)
Note

QC 20240314

Available from: 2024-03-13 Created: 2024-03-13 Last updated: 2024-03-14Bibliographically approved
Zeglio, E., Wang, Y., Jain, S., Lin, Y., Avila Ramirez, A. E., Feng, K., . . . Herland, A. (2024). Mixing Insulating Commodity Polymers with Semiconducting n‐type Polymers Enables High‐Performance Electrochemical Transistors. Advanced Materials, Article ID adma.202302624.
Open this publication in new window or tab >>Mixing Insulating Commodity Polymers with Semiconducting n‐type Polymers Enables High‐Performance Electrochemical Transistors
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2024 (English)In: Advanced Materials, ISSN 0935-9648, E-ISSN 1521-4095, article id adma.202302624Article in journal (Refereed) Published
Abstract [en]

Diluting organic semiconductors with a host insulating polymer is used to increase the electronic mobility in organic electronic devices, such as thin film transistors, while considerably reducing material costs. In contrast to organic electronics, bioelectronic devices such as the organic electrochemical transistor (OECT) rely on both electronic and ionic mobility for efficient operation, making it challenging to integrate hydrophobic polymers as the predominant blend component. This work shows that diluting the n-type conjugated polymer p(N-T) with high molecular weight polystyrene (10 KDa) leads to OECTs with over three times better mobility-volumetric capacitance product (µC*) with respect to the pristine p(N-T) (from 4.3 to 13.4 F V−1 cm−1 s−1) while drastically decreasing the amount of conjugated polymer (six times less). This improvement in µC* is due to a dramatic increase in electronic mobility by two orders of magnitude, from 0.059 to 1.3 cm2 V−1 s−1 for p(N-T):Polystyrene 10 KDa 1:6. Moreover, devices made with this polymer blend show better stability, retaining 77% of the initial drain current after 60 minutes operation in contrast to 12% for pristine p(N-T). These results open a new generation of low-cost organic mixed ionic-electronic conductors where the bulk of the film is made by a commodity polymer.

Place, publisher, year, edition, pages
Wiley, 2024
National Category
Polymer Technologies Materials Engineering Nano Technology Polymer Chemistry
Identifiers
urn:nbn:se:kth:diva-345903 (URN)10.1002/adma.202302624 (DOI)2-s2.0-85187136336 (Scopus ID)
Funder
Knut and Alice Wallenberg Foundation, KAW2015.0178 2020.0206Knut and Alice Wallenberg Foundation, 2021.0312Swedish Research Council, 2018–03483Swedish Research Council, 2022‐04060Swedish Research Council, 2022‐02855Karolinska Institute, 1‐249/2019KTH Royal Institute of Technology, VF‐2019‐0110
Note

QC 20240429

Available from: 2024-04-25 Created: 2024-04-25 Last updated: 2024-04-29Bibliographically approved
Jain, S., Voulgaris, D., Thongkorn, S., Hesen, R., Hägg, A., Moslem, M., . . . Herland, A. (2024). On‐Chip Neural Induction Boosts Neural Stem Cell Commitment: Toward a Pipeline for iPSC‐Based Therapies. Advanced Science, Article ID advs.202401859.
Open this publication in new window or tab >>On‐Chip Neural Induction Boosts Neural Stem Cell Commitment: Toward a Pipeline for iPSC‐Based Therapies
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2024 (English)In: Advanced Science, E-ISSN 2198-3844, article id advs.202401859Article in journal (Refereed) Published
Abstract [en]

The clinical translation of induced pluripotent stem cells (iPSCs) holds great potential for personalized therapeutics. However, one of the main obstacles is that the current workflow to generate iPSCs is expensive, time-consuming, and requires standardization. A simplified and cost-effective microfluidic approach is presented for reprogramming fibroblasts into iPSCs and their subsequent differentiation into neural stem cells (NSCs). This method exploits microphysiological technology, providing a 100-fold reduction in reagents for reprogramming and a ninefold reduction in number of input cells. The iPSCs generated from microfluidic reprogramming of fibroblasts show upregulation of pluripotency markers and downregulation of fibroblast markers, on par with those reprogrammed in standard well-conditions. The NSCs differentiated in microfluidic chips show upregulation of neuroectodermal markers (ZIC1, PAX6, SOX1), highlighting their propensity for nervous system development. Cells obtained on conventional well plates and microfluidic chips are compared for reprogramming and neural induction by bulk RNA sequencing. Pathway enrichment analysis of NSCs from chip showed neural stem cell development enrichment and boosted commitment to neural stem cell lineage in initial phases of neural induction, attributed to a confined environment in a microfluidic chip. This method provides a cost-effective pipeline to reprogram and differentiate iPSCs for therapeutics compliant with current good manufacturing practices.

This study highlights the development of a microfluidic platform to reprogram somatic cells from donors into induced pluripotent stem cells and further differentiate them into neural stem cells. This confined microfluidic platform boosts neural stem cell generation commitment at an early stage, as denoted by the pathway enrichment analysis. image

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2024
National Category
Medical Engineering Nano Technology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-345904 (URN)10.1002/advs.202401859 (DOI)001207250500001 ()
Funder
Lund University, StemTherapyThe Swedish Brain Foundation, FO2021‐0234The Swedish Brain Foundation, FO2022‐0151Knut and Alice Wallenberg Foundation, KAW2015.0178Knut and Alice Wallenberg Foundation, 2020.0206Knut and Alice Wallenberg Foundation, 2021.0312Swedish Research Council, 2018‐06169Swedish Research Council, 2019‐01498Swedish Research Council, 2022‐01362Karolinska Institute, 1‐249/2019KTH Royal Institute of Technology, VF‐2019‐0110Vinnova, 2021–02695
Note

QC 20240429

Available from: 2024-04-25 Created: 2024-04-25 Last updated: 2024-04-29Bibliographically approved
Kavand, H., Visa, M., Köhler, M., van der Wijngaart, W., Berggren, P. & Herland, A. (2023). 3D‐Printed Biohybrid Microstructures Enable Transplantation and Vascularization of Microtissues in the Anterior Chamber of the Eye. Advanced Materials
Open this publication in new window or tab >>3D‐Printed Biohybrid Microstructures Enable Transplantation and Vascularization of Microtissues in the Anterior Chamber of the Eye
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2023 (English)In: Advanced Materials, ISSN 0935-9648, E-ISSN 1521-4095Article in journal (Refereed) Published
Abstract [en]

Hybridizing biological cells with man-made sensors enable the detection of a wide range of weak physiological responses with high specificity. The anterior chamber of the eye (ACE) is an ideal transplantation site due to its ocular immune privilege and optical transparency, which enable superior non-invasive longitudinal analyses of cells and microtissues. Engraftment of biohybrid microstructures in the ACE might, however, be affected by the pupillary response and dynamics. Here, sutureless transplantation of biohybrid microstructures, 3D printed in IP-Visio photoresin, containing a precisely localized pancreatic islet to the ACE of mice is presented. The biohybrid microstructures allow mechanical fixation in the ACE, independent of iris dynamics. After transplantation, islets in the microstructures successfully sustain their functionality for over 20 weeks and become vascularized despite physical separation from the vessel source (iris) and immersion in a low-viscous liquid (aqueous humor) with continuous circulation and clearance. This approach opens new perspectives in biohybrid microtissue transplantation in the ACE, advancing monitoring of microtissue-host interactions, disease modeling, treatment outcomes, and vascularization in engineered tissues.

Place, publisher, year, edition, pages
Wiley, 2023
National Category
Medical Materials
Identifiers
urn:nbn:se:kth:diva-338013 (URN)10.1002/adma.202306686 (DOI)
Note

QC 20231012

Available from: 2023-10-12 Created: 2023-10-12 Last updated: 2023-10-12Bibliographically approved
Zhu, Y., Nasiri, R., Davoodi, E., Zhang, S., Saha, S., Linn, M., . . . Khademhosseini, A. (2023). A Microfluidic Contact Lens to Address Contact Lens-Induced Dry Eye. Small, 19(11), Article ID 2207017.
Open this publication in new window or tab >>A Microfluidic Contact Lens to Address Contact Lens-Induced Dry Eye
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2023 (English)In: Small, ISSN 1613-6810, E-ISSN 1613-6829, Vol. 19, no 11, article id 2207017Article in journal (Refereed) Published
Abstract [en]

The contact lens (CL) industry has made great strides in improving CL-wearing experiences. However, a large amount of CL wearers continue to experience ocular dryness, known as contact lens-induced dry eye (CLIDE), stemming from the reduction in tear volume, tear film instability, increased tear osmolarity followed by inflammation and resulting in ocular discomfort and visual disturbances. In this article, to address tear film thinning between the CL and the ocular surface, the concept of using a CL with microchannels to deliver the tears from the pre-lens tear film (PrLTF) to the post-lens ocular surface using in vitro eye-blink motion is investigated. This study reports an eye-blink mimicking system with microfluidic poly(2-hydroxyethyl methacrylate) (poly(HEMA)) hydrogel with integrated microchannels to demonstrate eye-blink assisted flow through microchannels. This in vitro experimental study provides a proof-of-concept result that tear transport from PrLTF to post-lens tear film can be enhanced by an artificial eyelid motion in a pressure range of 0.1–5 kPa (similar to human eyelid pressure) through poly(HEMA) microchannels. Simulation is conducted to support the hypothesis. This work demonstrates the feasibility of developing microfluidic CLs with the potential to help prevent or minimize CLIDE and discomfort by the enhanced transport of pre-lens tears to the post-lens ocular surface.

Place, publisher, year, edition, pages
Wiley, 2023
Keywords
contact lens-induced dry eyes, microchannels, microfluidic, ocular healthcare, smart contact lenses
National Category
Ophthalmology Nano Technology
Identifiers
urn:nbn:se:kth:diva-330099 (URN)10.1002/smll.202207017 (DOI)000903646800001 ()36564357 (PubMedID)2-s2.0-85145098728 (Scopus ID)
Note

QC 20230626

Available from: 2023-06-26 Created: 2023-06-26 Last updated: 2023-06-26Bibliographically approved
Matthiesen, I., Jury, M., Rasti Boroojeni, F., Ludwig, S., Holzreuter, M., Buchmann, S., . . . Herland, A. (2023). Astrocyte 3D culture and bioprinting using peptide functionalized hyaluronan hydrogels. Science and Technology of Advanced Materials, 24(1), Article ID 2165871.
Open this publication in new window or tab >>Astrocyte 3D culture and bioprinting using peptide functionalized hyaluronan hydrogels
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2023 (English)In: Science and Technology of Advanced Materials, ISSN 1468-6996, E-ISSN 1878-5514, Vol. 24, no 1, article id 2165871Article in journal (Refereed) Published
Abstract [en]

Astrocytes play an important role in the central nervous system, contributing to the development of and maintenance of synapses, recycling of neurotransmitters, and the integrity and function of the blood-brain barrier. Astrocytes are also linked to the pathophysiology of various neurodegenerative diseases. Astrocyte function and organization are tightly regulated by interactions mediated by the extracellular matrix (ECM). Engineered hydrogels can mimic key aspects of the ECM and can allow for systematic studies of ECM-related factors that govern astrocyte behaviour. In this study, we explore the interactions between neuroblastoma (SH-SY5Y) and glioblastoma (U87) cell lines and human fetal primary astrocytes (FPA) with a modular hyaluronan-based hydrogel system. Morphological analysis reveals that FPA have a higher degree of interactions with the hyaluronan-based gels compared to the cell lines. This interaction is enhanced by conjugation of cell-adhesion peptides (cRGD and IKVAV) to the hyaluronan backbone. These effects are retained and pronounced in 3D bioprinted structures. Bioprinted FPA using cRGD functionalized hyaluronan show extensive and defined protrusions and multiple connections between neighboring cells. Possibilities to tailor and optimize astrocyte-compatible ECM-mimicking hydrogels that can be processed by means of additive biofabrication can facilitate the development of advanced tissue and disease models of the central nervous system.

Place, publisher, year, edition, pages
Informa UK Limited, 2023
Keywords
Astrocytes, 3d cell culture, bioprinting, hyaluronan, cRGD, IKVAV
National Category
Neurosciences
Identifiers
urn:nbn:se:kth:diva-324537 (URN)10.1080/14686996.2023.2165871 (DOI)000919345500001 ()36733710 (PubMedID)2-s2.0-85148446005 (Scopus ID)
Note

QC 20230307

Available from: 2023-03-07 Created: 2023-03-07 Last updated: 2023-03-07Bibliographically approved
Roberto de Barros, N., Nasiri, R., Herland, A., Khademhosseini, A. & et al., . (2023). Engineered organoids for biomedical applications. Advanced Drug Delivery Reviews, 203, Article ID 115142.
Open this publication in new window or tab >>Engineered organoids for biomedical applications
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2023 (English)In: Advanced Drug Delivery Reviews, ISSN 0169-409X, E-ISSN 1872-8294, Vol. 203, article id 115142Article, review/survey (Refereed) Published
Abstract [en]

As miniaturized and simplified stem cell-derived 3D organ-like structures, organoids are rapidly emerging as powerful tools for biomedical applications. With their potential for personalized therapeutic interventions and high-throughput drug screening, organoids have gained significant attention recently. In this review, we discuss the latest developments in engineering organoids and using materials engineering, biochemical modifications, and advanced manufacturing technologies to improve organoid culture and replicate vital anatomical structures and functions of human tissues. We then explore the diverse biomedical applications of organoids, including drug development and disease modeling, and highlight the tools and analytical techniques used to investigate organoids and their microenvironments. We also examine the latest clinical trials and patents related to organoids that show promise for future clinical translation. Finally, we discuss the challenges and future perspectives of using organoids to advance biomedical research and potentially transform personalized medicine.

Place, publisher, year, edition, pages
Elsevier B.V., 2023
Keywords
Disease modeling, Organoids, Regenerative medicine, Spheroids, Stem cell, Therapies
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-340353 (URN)10.1016/j.addr.2023.115142 (DOI)001118648100001 ()37967768 (PubMedID)2-s2.0-85177490094 (Scopus ID)
Note

QC 20231204

Available from: 2023-12-04 Created: 2023-12-04 Last updated: 2024-01-03Bibliographically approved
Tujula, I., Hyvarinen, T., Lotila, J., Jantti, H., Ohtonen, S., Sukki, L., . . . Hagman, S. (2023). Human iPSC glial co-culture chip model for studying neuroinflammation in vitro. Paper presented at 16th European Meeting on Glial Cells in Health and Disease, JUL 08-11, 2023, Berlin, GERMANY. Glia, 71, E964-E964
Open this publication in new window or tab >>Human iPSC glial co-culture chip model for studying neuroinflammation in vitro
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2023 (English)In: Glia, ISSN 0894-1491, E-ISSN 1098-1136, Vol. 71, p. E964-E964Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
John Wiley & Sons, 2023
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:kth:diva-345570 (URN)001191372500811 ()
Conference
16th European Meeting on Glial Cells in Health and Disease, JUL 08-11, 2023, Berlin, GERMANY
Note

QC 20240415

Available from: 2024-04-15 Created: 2024-04-15 Last updated: 2024-04-15Bibliographically approved
Herland, A. (2023). Invited speaker Combining Stem Cell and Device Engineering for In vitro Models of Human Physiology. European Biophysics Journal, 52(SUPPL 1), S29-S29
Open this publication in new window or tab >>Invited speaker Combining Stem Cell and Device Engineering for In vitro Models of Human Physiology
2023 (English)In: European Biophysics Journal, ISSN 0175-7571, E-ISSN 1432-1017, Vol. 52, no SUPPL 1, p. S29-S29Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
SPRINGER, 2023
National Category
Biophysics
Identifiers
urn:nbn:se:kth:diva-335955 (URN)001029235400029 ()
Note

QC 20230911

Available from: 2023-09-11 Created: 2023-09-11 Last updated: 2023-09-11Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-5002-2537

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