This study introduces a pioneering approach for transplanting biohybrid microstructures into the anterior chamber of the eye. This technique combines biological cells with sensors to detect subtle physiological responses with precision. Overcoming challenges related to pupillary dynamics, the method ensures secure transplantation and prolonged functionality of microstructures housing pancreatic islets. Even more striking, these islets develop a blood supply, offering exciting prospects for improved disease modeling, treatment efficacy, and engineered tissue vascularization. This breakthrough redefines possibilities in bioengineering and regenerative medicine, providing hope for enhanced medical treatments.
The Herland Lab spent an intense and enjoyable week in Berlin, Germany at Microphysiological Society World Summit which was held together with the European Organ-on-Chip conference.
Sebastian gave a talk in the session on “Microfabrication, Instrumentation & Sensors” and Laura presented the work done as a part of master thesis in the session on “MPS for Vascularization”. Julia, Rohollah, Saumey, and Begum presented posters with their latest research results.
Julia, Begum, Sebastian and Laura were also awarded travel grants.
In this work, we have developed a 3D-printed platform that enables precise control and in-depth study of the interaction between astrocytes and neurons. To achieve this, we utilized a commercially available printing resin IP-Visio (Nanoscribe), with non-autofluorescent and non-cytotoxic properties. We successfully printed a neurite guidance platform, which served as a guiding structure for the outgrowth of neurites from neurons. By employing a probabilistic two-step cell seeding approach, we were then able to control the interaction points between neurons and astrocytes. This innovative approach simplifies the modeling of complex brain interactions, thereby facilitating further advancements in biomedical research and enhancing our understanding of the human brain.
Herland Lab participated at the Swedish Microfluidics in Life Science conference in Stockholm on the 30th and 31st of May. Laura and Rohollah had oral presentations, whereas Yunfan, Monika, and Salem presented their research as posters. It was a great opportunity to network with the microfluidics network in Sweden as well as the neighboring countries.
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.
Dr. Erica Zeglio was admitted as a Docent in Bioelectronic Materials at KTH. She gave the docent lecture on ‘Organic bioelectronics: from sustainable materials chemistry to the interface with biology.’ The docentship in the Swedish system means she can supervise and be an opponent for a PhD candidate and is not supposed to lose badly.
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.
Prof. Anna Herland and Dr. Erica Zeglio are awarded grants from the Swedish Research Council (Vetenskaprådet).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
We have an open Postdoc (scholarship) position in the field of electrochemical biosensors. The post doc scholarship will focus on organic electrochemical transistors-based biosensors for the enzymatic sensing of small molecules. For more details and application, check the link below.
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.
Erica Zeglio, our post-doc was featured in an interview with Vattenfall, a Swedish energy company where she gave a comment about an innovative technology for power generation using conducting bacterial nanowires.
Congratulations to our postdoc Erica Zeglio on being awarded a prestigious Marie Skłodowska-Curie Individual Fellowship by the European Commission for her project entitled “BioResORGEL: Bioresorpable Organic Electronic Devices”.
We have another open Postdoc (scholarship) position in the Wallenberg foundation funded project Organs-on-Chips for Translational Research in Brain Disease. The post doc scholarship will focus on developing and integrating sensors in Brain-on-Chip systems using conventional cell culture and microfluidic Organ-on-Chip methods. More details can be found here.
Organs-on-Chips will be critical to reducing animal experiments in the future. There are manychallenges 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
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.
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.
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.
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.
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.
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.
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.
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-negativebacteria, holding immense potential in the field of hygiene products and medical devices.
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.