Laura awarded the Best Pitch Award at the Nordic Organ-on-Chip Networking Event

Laura Benito-Zarza pitched her master thesis work today during the Nordic Organ-on-Chip networking event and won one of the best pitch awards, consisting of a travel grant in the Nordics to expand her network and experience in the Organ-on-Chip field. She is supervised by Dr. Julia Rogal and Dr. Alessandro Enrico and working to develop a hiPSC-derived microvascularized tissue model to recapitulate in vivo complexity for the study and treatment of complex diseases, such as Parkinson’s and Alzheimer’s.

Congratulations Laura!

New paper published in Science and Technology of Advanced Materials

A new paper titled ‘Astrocyte 3D culture and bioprinting using peptide functionalized hyaluronan hydrogels‘ was published in Science and Technology of Advanced Materials today.

This work highlights the development of peptide functionalized hyaluronan hydrogels for bioprinting. The study utilized neuroblastoma (SH-SY5Y) and glioblastoma (U87) cell lines and human fetal primary astrocytes (FPA) with a modular hyaluronan-based hydrogel system. It was observed that FPA had a higher degree of interaction with the hyaluronan-based gels compared to the cell lines. These engineered hydrogels enable the possibilities to bioprint, culture and maintain FPA and can thus facilitate the development of more elaborate neural and astrocytic tissue and disease models.

link to article

Research Grants awarded to Herland Lab

Prof. Anna Herland and Dr. Erica Zeglio are awarded grants from the Swedish Research Council (Vetenskaprådet).

  1. Refining neurovascular in vitro models  (Prof. Anna Herland, co PIs: Ryan Hicks (AstraZeneca), Xenia Nikolakopoulou (KI), Jane Synnergren (University of Skövde))

All new drug candidates need to be evaluated for central nervous system (brain) penetration and sideeffects. Unfortunately, and especially for new drug types, the testing methods do not show how the drugs will work in humans. Here, we focus on developing and validating human functional Organ-on-Chip models of the brain and its vasculature. In this work, which is a collaboration with AstraZeneca around the theme to reduce and refine animal experiments, we especially focus on human specific drugs including viral vectors and protein or peptide-based drugs. 

2. 2D and 3D in vitro models with organic electronic interfaces to electrogenic cells (PI: Prof. Anna Herland, co PIs: Prof. Max Hamedi (KTH), Prof. Frank Nikalus (KTH) and Dr. Erica Zeglio (KTH))

Electrodes are needed to stimulate and measure on electrically active tissues, such as the heart and brain. Electrodes are specifically used in electrophysiology, the studies of electrically active cells outside the body. This is an essential method in drug development and toxicity studies. 

 The main goal in this project is to create new methods to carry out electrophysiology in 3D and microfluidic cell culture, so called Organ-on-Chips. We will combine the development of new polymer materials, new transistor designs, and new fabrication methods for electroactivity measurements in 2D and 3D systems. 

3. Biodegradable electronic polymers: from device components to in vivo monitoring technologies (VR Starting Grant, Dr. Erica Zeglio)

Temporary implants are currently based on electronics that dissolve in contact with water, limiting their application in contact with (water-based) biological fluids. With the project “Biodegradable electronic polymers: from device components to in vivo monitoring technologies”, the Team led by Dr. Zeglio will investigate device components that are stable in contact with water and degrade into nontoxic products by the action of living cells.

New paper published in Biosensors

The article titled “Metabolic Assessment of Human Induced Pluripotent Stem Cells-Derived Astrocytes and Fetal Primary Astrocytes: Lactate and Glucose Turnover” was published in Biosensors today.

Astrocytes are one of the key cell types in brain for energy metabolism. In this research article, the metabolic parameters of astrocytes derived from two common sources including induced pluripotent stem cells (hiPSCs) and human fetal primary astrocytes (HFAs) were studied in a defined media. The glucose uptake and lactate production in astrocytes derived from hiPSC to HFA were compared using a flow-through biosensor. The study concluded that hiPSC-derived astrocytes are as glycogenic as their fetal counterparts, but their normalized metabolic turnover is lower.

link to the article

Welcome Kim and Yunfan!

Herland Lab (re)welcomes Kim and Yunfan after completing their Masters! Kim Roekevisch is back as a Research Engineer at KI, working on the targeting of the CNS using AAVs with Xenia and Julia. Yunfan Lin is also back as a Research Engineer at KTH, working on the development of biodegradable electrochemical sensors for food monitoring with Erica and Anna.

Welcome back Kim and Yunfan!

New paper published in Advanced Materials

The article “3D Microvascularized Tissue Models by Laser-Based Cavitation Molding of Collagen” was published in Advanced Materials on January 14th.

A long-standing question in tissue engineering is how to vascularize tissue models. This study made a breakthrough with a technology that can enable much more physiological vascularization. The article reports a novel patterning approach for collagen hydrogels, referred to as “cavitation molding”, to create 3D cavities that can be used as a template to form the microvasculature. This method enables the fabrication of relevant models to study complex tissue, such as tumors and neural tissue.

Vascularized cancer-on-a-chip model developed using cavitation molding of collagen

New Postdoctoral Scholar joins the group

Dr. Julia Rogal has joined the Herland Lab as a new postdoctoral scholar at the beginning of the month. Julia received her BSc degree in Biology and MSc degree in Biomedical Engineering from RWTH Aachen University in Germany. In 2021, she got her Ph.D. in biology from the Eberhard Karls University in Tübingen, Germany.

In the Herland Lab, Julia will focus on developing patient-specific iPSC-based blood-brain barrier models for disease modeling and drug screening applications.

New paper published in Advanced Functional Materials

The article “Green Synthesis of Lactone-Based Conjugated Polymers for n-Type Organic Electrochemical Transistors” was published in Advanced Functional Materials today.

This research article highlights a new design strategy for n-type organic semiconductors combining sustainable synthesis with the high ionic/electronic conductivity needed for organic electrochemical transistors (OECT). The use of electron-deficient lactone building blocks allowed synthesis via Aldol polymerization, offering the advantage of avoiding toxic and environmentally harmful compounds, such as the organotin reagents commonly used in Stille polymerization. These conjugated polymers are an excellent choice for n-type OECTs, pushing towards a new generation of high-performing materials that are better for the environment.

link to the article

New review article in Advanced Materials

A new review article titled ‘Advanced Materials and Sensors for Microphysiological Systems: Focus on Electronic and Electro-optical Interfaces‘ was published in Advanced Materials today.

Advanced in vitro cell culture, microphysiological systems (MPSs), recapitulate features of human tissues and are increasingly being used for drug development and disease modeling. Still, they are commonly based on standard polymers with minimal real-time stimuli and read-out capacity. This review article describes how advanced materials and devices could enable a technology leap in reproducing in vivo-like functionality and real-time tissue monitoring.

link to the article

New review article in Chemical Reviews

A review article titled “Current Progress of Interfacing Organic Semiconducting Materials with Bacteria” was published in Chemical Reviews today.

This review article summarizes the biological and electronic considerations when interfacing organic semiconductors with bacteria. From the biological perspective, it highlights the various mode employed by bacteria to communicate with the environment and with other bacteria. From the application perspective, it summarizes the characterization techniques and device geometries used to interface organic electronics with bacteria.

link to the article

New paper published in ACS Applied Materials & Interfaces

The article “Sorption of Neuropsychopharmaca in Microfluidic Materials for In Vitro Studies” was published in ACS Applied Materials & Interfaces today. The study highlights the impact of peristaltic pump tubing in sorption of hydrophobic compounds. mainly consisting of neuropsychopharmaca. The article further displays that the use of PDMS or other device construction methods OSTE+ or PC/PSA had a similar effect on the sorption, whereas the material of the tubing had a stronger dependence on sorption as compared to the device material. This signifies that the tubing and associated materials deserve similar attention as other device materials used for in-vitro studies.

link to the article

New Postdoctoral scholar joins the group

Dr. Rohollah Nasiri joins the Herland group as our newest postdoctoral scholar. He received his PhD and MSc degrees in Mechanical Engineering from the Sharif University of Technology, Iran, in 2021 and 2014, respectively. His research focusses on designing organ-on-a-chip devices integrated with biosensors for disease modeling and drug screening applications.

New paper published in the Journal of Materials Chemistry C

The article “Rapid prototyping of heterostructured organic microelectronics using wax printing, filtration, and transfer” was published in the Journal of Materials Chemistry C today. The research highlights rapid prototyping of various micropatterned organic electronic heterostructures of PEDOT:PSS using hydrogels filtered onto membranes containing hydrophobic wax patterns. The article also demonstrates the potential of this method for micro-supercapacitors, organic electronic transistors, and their use in cell culture to enable bioelectronics.

The article was also featured on the front cover of the journal.

link to the article

link to the front cover

New paper published in Small

The article “Continuous Monitoring Reveals Protective Effects of N-Acetylcysteine Amide on an Isogenic Microphysiological Model of the Neurovascular Unit” was published in Small today. The article reports a microphysiological blood-brain barrier model that captures the multicellular interactions of iPS-derived cells. The integrated electrical sensors, facilitated by PDMS-free fabrication, allow for real-time monitoring of how the barrier responds to oxidative stress and antioxidant prophylaxis. The sensor integrated hiBBB-on-chip displayed an immediate utility in the screening of drugs modulating the barrier by providing readout about the temporal pharmacodynamic profiles.

The article was also featured on the inside Back cover of the journal.

link to the article

link to the cover

Inside Back cover of SMALL

Open Post doc position at Herland Lab

We have an open Postdoc (scholarship) position in the Wallenberg foundation funded project Organs-on-Chips for Translational Research in Brain Disease. This project will be focusing on inborn errors of metabolism in children, combining neural models with real-time sensing of neural function, barrier function and metabolic activity. Conventional cell culture, as well as microfluidic Organ-on-Chip methods will be applied. The post doc scholarship will focus on developing functional stem-cell derived cells for modelling inborn errors of metabolism combined with Brain-on-Chip systems. The postdoc will work closely together with engineers in the Herland lab and clinical researchers at Karolinska Hospital. More details can be found here.

Link to the advertisement on KTH webpage

New Article published in International Journal of Molecular Sciences

The article “Bisphenol A Inhibits the Transporter Function of the Blood-Brain Barrier by Directly Interacting with the ABC Transporter Breast Cancer Resistance Protein (BCRP)” was published in the International Journal of Molecular Sciences today. The article highlights that bisphenol A (BPA), a widely used chemical in consumer products affects the transport function of breast cancer resistance protein (BCRP). This effect is suggestive to BPA’s known detrimental impact on neurodevelopment.

link to the article on MDPI

New Article Published in Nature Physics

The article “Fluid interfacial energy drives the emergence of three-dimensional periodic structures in micropillar scaffolds” was published in Nature Physics today. The article highlights an elegant design and building approach of periodic three-dimensional multi-material fluid lattice architectures which can also be used for composites, droplet networks and can also support the growth of biological cells and tissues.

link to the article in Nature Physics

link to the news highlight on the article

Research featured in ATLA (Alternatives to Laboratory Animals)

Our recent research article titled ‘Low-cost microphysiological systems: feasibility study of a tape-based barrier-on-chip for small intestine modeling‘ which was published in Lab on a Chip earlier this year, was featured in the News and Views section of the journal ATLA (Alternatives to Laboratory Animals).

Organs-on-Chips will be critical to reducing animal experiments in the future. There are many challenges still to overcome toward their widespread use, one important challenge being the high cost and complexity of manufacturing current systems, both commercially or in an academic setting. In our work, we showcase a functional Barrier-on-Chip of the small intestine, fabricated using very simple and low-cost methods that practically anyone can implement in their lab, but that can also be adapted to large-scale industrial manufacture. We hope that this can make Barrier-on-Chip technology much more broadly accessible, particularly to researchers and prototypers in low-resource environments.

Comments from Prof. Anna Herland on the feature in ATLA

Link to the feature in ATLA (Alternatives to Laboratory Animals)

Link to the original research article in Lab on a Chip

New Master’s student joins the group

Violetta Nikiforova joins the Herland group as our newest master’s student. She is currently enrolled in the Master’s programme in Toxicology at Karolinska Institutet. For her thesis, she will be working with Xenia on the development and validation of novel in-vitro models for adverse effects on the human neurovascular unit.

New Master’s students join the group

Today, Saskia Ludwig and Eleni Stergiou join the Herland group as our newest Master’s students. Saskia is pursuing a Master’s degree in Fundamental Neuroscience at Maastricht University in the Netherlands and will work on her thesis with Isabelle on spontaneous differentiation of neuroepithelial stem cells in 3D hydrogels at KTH. Eleni is currently pursuing a Master’s degree in Molecular Medicine at Uppsala University and will work on her thesis with Xenia on the development of hiPSC-based in-vitro models of neurovascular unit for screening and investigation of novel drug modalities.

New review article published in Brain

An extensive review article “Recent progress in translational engineered in vitro models of the central nervous system” was published in Brain today. Together with Ben M.Maoz and his group at the Tel Aviv University, we discuss the recent developments in in-vitro CNS models with focus on combined microfluidics and cell culture systems (e.g. ‘organ-on-a-chip’ systems). The article also highlights the challenges hindering the advancement of this field and its large-scale acceptance and implementation and underlines some practical guidelines for labs venturing into this field.

link to the article

New perspective article published in Nature

The perspective article “LifeTime and improving European healthcare through cell-based interceptive medicine” was published in Nature today. The LifeTime Initiative consists of experts from varied disciplines from over ninety research institutes from all over the EU. The initiative aims to develop and integrate novel technologies such as patient-derived experimental disease models, single-cell multi-omics, high content imaging and artificial intelligence to address the current medical challenges and incorporate them into regular laboratory and clinical workflows resulting in a great benefit for healthcare providers and patients alike.

link to the article on Nature

New paper published in Advanced Biosystems

The article “Proteomic and Metabolomic Characterization of Human Neurovascular Unit Cells in Response to Methamphetamine” was published in the Advanced Biosystems today. The research highlights the effect of methamphetamine on the proteomic and metabolomic properties of constituent cells of the neurovascular unit, especially those of human pericytes not reported previously. This work presents new pathways that are active in the cells at homeostasis and as a response to Meth, which could be important when studying the detrimental effects of Meth intoxication on the CNS.

link to the article in Advanced Biosystems

New review article published in Molecular and Cellular Neuroscience

The review article “Models of the blood-brain barrier using iPSC-derived cells” was published in Molecular and Cellular Neuroscience today. The article discusses the capability for the use of human iPSC- derived brain cells for modelling the blood-brain barrier (BBB) over the conventionally used immortalized brain endothelial cell lines and primary brain endothelial cells of human and animal origin. The review highlights the essential functions of the BBB and the ongoing efforts in the creation of iPSC-derived BBB models along with the key requirements and challenges faced currently.

link to the article in Molecular and Cellular Neuroscience

New paper published in Micromachines

The article “Low-Cost PVD Shadow Masks with Submillimeter Resolution from Laser-Cut Paper” was published in Micromachines today. The research highlights an affordable method to produce shadow masks for physical vapor deposition using cellulose filter paper and CO2 laser processing. These masks are shown to be stable and resilient in processing and handling. This method holds a lot of potential for a range of applications such as electrochemical cells and contact pads for organic electronic materials where submillimeter PVD features are required.

Link to the original article at Micromachines

New paper published in ACS Omega

The article “Electrochemical Detection of Genomic DNA Utilizing Recombinase Polymerase Amplification and Stem-Loop Probe” was published in the ACS Omega today. The research illustrates a method to integrate isothermal DNA amplification, recombinase polymerase amplification to an electrochemical stem-loop probe DNA detection technique while reducing the need for purification of the amplified product and improving the sensitivity and limit of detection.

link to the article in ACS Omega

New paper published in the Journal of Colloid and Interface Science

The article “Bactericidal surfaces prepared by femtosecond laser patterning and layer-by-layer polyelectrolyte coating” was published in the Journal of Colloid and Interface Science today. The research focusses on the modification of borosilicate glass surfaces through µm-scale patterning using ultrashort pulsed laser irradiation and a layer-by-layer polyelectrolyte modification of the surface with charge values at least 10 times lower than the previously reported cationic bactericidal surfaces. This method yields enhanced bactericidal effect against both Gram-positive and Gram-negative bacteria, holding immense potential in the field of hygiene products and medical devices.

Link to the article in the Journal of Colloid and Interface Science

New paper published in Advanced Biosystems

The article “hiPS‐Derived Astroglia Model Show Temporal Transcriptomic Profile Related to Human Neural Development and Glia Competence Acquisition of a Maturing Astrocytic Identity” was published in the Advanced Biosystems today. The research highlights the directed differentiation of neuroepithelial stem cells undergoing a neurogenic-to-gliogenic competence. This NES-Astro model can be used for detailed mechanistic studies of RG and astrocyte development under normal conditions in addition to disease models.

link to the article in Advanced Biosystems

New paper published in Lab on a Chip

The article “Low-cost microphysiological systems: Feasibility study of a tape-based barrier-on-chip system for small intestine modeling” was published in Lab on a Chip today. The research highlights the use of simple double-sided tape to assemble an organ-on-a-chip system with human gut as a model, replacing the typically used expensive techniques and materials. This method will prove to be a robust and reproducible approach to studying physiological barriers, promising faster development of new drugs and precision and personalized medicine.

Link to the article in Lab on a Chip

Link to KTH Press Release

Link to the back cover in Lab on a Chip

Back cover, Lab Chip, 2020,20

New paper published in the Journal of Visualized Experiments (JoVE)

The article “Generation of a Human iPSC-Based Blood-Brain Barrier Chip” was published in the Journal of Visualized Experiments (JoVE) today. The research illustrates the possibility to combine organ-on-chip and induced pluripotent stem cell (iPSC) technologies to generate a BBB chip fully personalized to human barrier formation on a functional and transcriptional level.

Generation of a Human iPSC-Based Blood-Brain Barrier Chip

Two new papers in Nature Biomedical Engineering

Two new articles on multi-organ in-vitro models developed in collaboration with the Wyss Institute were just published in Nature Biomedical Engineering as part of a collection on Microphysiological Systems: “Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips” and “Robotic fluidic coupling and interrogation of multiple vascularized organ chips“. These platforms could drastically accelerate drug testing and provide accurate predictions of drug effects prior to clinical testing.

link to KTH press release

link to Wyss Institute press release

Thomas at the European Research and Innovation Days

Thomas pitched his (and the lab’s) research at the Marie Curie Falling Walls Lab in Brussels as part of the European Research and Innovation Days. He and the other 29 participants (selected from over 200 applicants) got the opportunity to present their research to a broad audience – in under 3 minutes each.

If you missed the live stream, you can watch his pitch here. The video is courtesy of the European Commission.