Outreach

• When: 14^th September @12:00-13:00 (talk starts 12:15)
• Where: In person (Å2001) or on Zoom (https://uu-se.zoom.us/j/65082613110)

Speakers: Maria Sörby, Director Clinical Research and Elisabeth Palmcrantz-Graf, Project Manager Clinical Research, both from Uppsala Clinical Research Center

Title: Clinical trials for medical device – how is it done?

Abstract: Uppsala Clinical Research center is the leading clinical Academic Research Organization (ARO) in Sweden, providing in-house expertise. Our services include management of clinical studies, biostatistics, clinical quality registries, and clinical event adjudication.

UCR started in 2001 as a clinical research center within Uppsala University and Uppsala University Hospital, with an aim to support qualified clinical research to improve health and healthcare practice.

The UCR experienced teams are knowledgeable in conducting both observational studies, in collaboration with regional, academic, or independent researchers, as well as large, global, complex, randomized clinical trials together with global medical corporations, in pharmaceuticals and medical devices.

The presentation will describe the basics for performing a clinical study, with a specific focus on medical device.

Bios: Maria Sörby is a biochemist and has a PhD in Molecular Cell Biology from the Ludwig Institute for Cancer Research at Uppsala University. She has experience as head of large-scale laboratories and Quality manager. Maria was the Site Director at SciLifeLab at Uppsala University, during the build-up years 2010-2016. Recently, Maria has been Project Manager for a national project developing and implementing a clinical decision support system in cancer care. Starting in 2023, Maria is Director Clinical Research at UCR.

Elisabeth Palmcrantz-Graf has a MSc in Biochemistry and Molecular Biology from Uppsala University. She has been working in the field of clinical research since 1995 and has experience from pharmaceutical and medical device industry, as well as from academic clinical research. Since 2006 she has been working as Project Manager at UCR.

Speaker: Dr. Niklas Sandström, Dept. of Applied Physics, KTH,  SciLifeLab

Title: Longitudinal screening and high-resolution imaging in microwells of 2D/3D live immune cell assays 

Abstract: Single-cell technologies have revolutionized research areas such as cancer and immune cell biology, enabling extensive characterization of phenotypic profiles of single cells revealing heterogeneity in supposed homogenous cell populations. Although such techniques, like transcriptomics and flow cytometry, are powerful tools for single-cell analysis, they are not capable of examining functional differences and responses to any great extent. In contrast, imaging allows longitudinal live cell assays with single-cell resolution. The use of multiwell plates enables high-content screening in a multitude of liquid conditions, but detailed functional studies of single-cells over time remains challenging. To address this issue, we have developed a range of microwell chips for live cell imaging assays with high optical quality where cells are confined for longitudinal studies. Our microwell platform enables screening and high-resolution imaging, which we utilize to investigate individual functional responses of natural killer cells in contact with tumor cells in different conditions. Our live cell assays in microwells involves 2D cell cultures as well as 3D tumor spheroid cultures and are aimed at applications within cell therapy and precision medicine. 

Bio: Niklas is a researcher at the Div. of Biophysics, Dept. of Applied Physics, KTH Royal Institute of Technology, SciLifeLab, in Stockholm, Sweden. He has a M.Sc. in Engineering Biology and a Ph.D. in Micro and Nanosystems/Electrical Measurements. Currently, he is leading the development of a microwell chip platform for efficient screening and high-resolution imaging of live cell assays and related research projects. With a keen interest in imaging, he also teaches photography for Media Technology students at KTH and works as an operations officer for the National Microscopy Infrastructure (NMI) in Sweden. 

Speaker: Assoc Prof. Oommen Varghese, Department of Chemistry, Uppsala University

Title: Soft extracellular matrix mimetic hydrogels for bone regeneration: Latest developments and future perspectives

Abstract: Soft hydrogels have emerged as a promising biomaterial for tissue regeneration due to their tunable mechanical properties and ability to mimic the extracellular matrix of natural tissues. Of particular interest is hyaluronic acid (HA) based materials for delivering stem cells and therapeutic proteins.  Hydrogels made from hyaluronic acid offer several advantages, including biocompatibility, biodegradability, and the ability to incorporate and deliver bioactive molecules. These properties make such hydrogels particularly attractive for applications such as wound healing, drug delivery, and tissue engineering. Incorporation of BMP-2 in hyaluronic acid hydrogels has shown great potential in bone tissue engineering as it enhances bone regeneration by promoting osteogenic differentiation of mesenchymal stem cells and stimulating new bone formation. We have recently shown that controlling the molecular interactions between BMP-2 and hyaluronic acid, it is possible to modulate controlled release of the protein and mitigate the potential side effects associated with higher doses of BMP-2, making it a safer and more effective approach for bone regeneration.

In this talk, I will provide recent updates in designing novel hydrogel with controlled swelling and degradation properties. I will also present the recent advances to overcome one of the limitations of soft hydrogels for bone regeneration i.e., the limitation to maintain the required shape of the defective tissue. These challenges are addressed with 3D printed scaffolds made of composite materials involving biopolymers and ceramic materials. Current clinical trials to regenerate large bone defects using BMP-2 will also be presented.

Bio: Dr. Oommen Varghese is an Associate Professor at the Department of Chemistry-Ångström Laboratory, Uppsala University in Sweden. With a PhD in Organic Chemistry from the same university, Dr. Varghese has demonstrated expertise in interdisciplinary research with a primary focus on regenerative medicine and targeted drug delivery. His research approach integrates synthetic organic chemistry and biotechnology to address critical problems in the field of regenerative medicine and anticancer therapeutics.

Dr. Varghese is a leading researcher and has (co-) authored more than 50 research articles in peer-reviewed international journals, and has filed several patents. He is widely recognized for his outstanding contributions to material science and nucleic acid therapeutics and has received numerous awards and honors for his exceptional work, including the prestigious ‘vision prize’ in 2014 for novel innovation at Uppsala University.

Dr. Varghese is a co-founder of a spin-off called ‘Uppsala Therapeutics’ and has filed several patents. He is a prominent leader in the field and his work has demonstrated how biomaterial design and delivery technologies can be utilized in bone regeneration applications. His current talk will highlight the recent advances in his research, which is expected to have significant contributions to the field of regenerative medicine.

Speaker: Dr. Sérgio Pequito, Department of Information Technology, Uppsala University

Title: Closed-loop electrical neurostimulation to mitigate abnormal neural behavior

Abstract: Electrical neurostimulation is an increasingly adopted therapeutic methodology for neurological conditions such as epilepsy and chronic pain. Nowadays, the devices automatically and dynamically deploy prespecified stimulation stimuli that were decided upon (offline) during a period of manual (and empirical) calibration. The stimulation stimuli are deployed upon the detection of abnormal neural activity due to, for example, seizures and chronic pain.

It is important to notice that the potential information contained in the measurements acquired is considerably underutilized, given that this type of stimulation strategy only entails an event-triggered relationship. Therefore, we must consider an online feedback (i.e., closed-loop) strategy. More precisely, the stimulation stimuli should be crafted based on the state of the neurophysiological system estimated from the data collected.

In this talk, we introduce a (mathematical) model-based approach for (real-time) closed-loop electrical neurostimulation, in which the evolution of the system is captured by a fractional-order system (FOS). More precisely, we propose a model predictive control (MPC) approach with an underlying FOS predictive model, due to the ability of fractional-order dynamics to more accurately capture the long-term dependence present in biological systems, compared to the standard linear time-invariant models. Furthermore, MPC offers, by design, an additional layer of robustness to compensate for system-model mismatch, which the more traditional strategies lack.

To establish the potential of our framework, we focus on epileptic seizure and chronic pain mitigation. Specifically, we consider in-silico settings and provide evidence of the effectiveness of our method on seizures and pain due to neuromas simulated by commonly adopted models in the neuroscience and medical community present in the literature. Our study thus paves the way for the development and implementation of robust real-time closed-loop electrical neurostimulation, which can then be used for the construction of more effective devices for both epileptic seizure and chronic pain mitigation.

Bio: Dr. Sérgio Pequito is an associate professor in automatic control in the Department of Information Technology, at Uppsala University. Pequito's research consists of understanding the global qualitative behavior of large-scale systems from their structural or parametric descriptions and provides a rigorous framework for the design, analysis, optimization, and control of large-scale systems. Currently, his interests span to neuroscience and biomedicine, where dynamical systems and control theoretic tools can be leveraged to develop new analysis tools for brain dynamics toward effective personalized medicine and improve brain-computer and brain-machine-brain interfaces. Pequito was awarded the best student paper finalist in the 48th IEEE Conference on Decision and Control (2009) and the 2016 O. Hugo Schuck Award in the Theory Category by the American Automatic Control Council.

Speaker: Adj. Prof. Philip Procter Department of Materials Science and Engineering, UU.

Title: From Screwing to gluing – Our Odyssey to find a viable musculoskeletal tissue glue.

Abstract: I will present the story of how, as a young product manager in an orthopaedic company making metal implants for the repair of broken bones, I begin the search for the dream orthopaedic biomaterial – a bone glue. How, after many years of patiently searching through adhesive candidates I eventually undertake research at UU that is successful and leads to the founding of Biomimetic Innovations - a company that is developing the worlds first bone adhesive. Nobody achieves something like this on their own and I will illustrate how serendipity as well as many talented people and in particular Sweden have all helped me find something that has eluded researchers for over 100 years. I have invited a UU colleague, Gry Hulsart Billström to help me illustrate this. I will conclude with a practical demonstration with OsStic our bone glue.

Bio: I am industry-based and a self-employed medical device consultant in France.  My main activity is translating biomaterials from the laboratory to clinical use to meet unmet clinical needs. I have co-founded two SME’s GPBio Ltd, (Ireland 2013) for developing adhesive biomaterials and Biomimetic Innovations Ltd, (Ireland 2020) which is currently commercialising OsSticR, a patented, adhesive platform technology with two multinational implant companies. I direct research into Biomimetic injectable biomaterials, Tissue adhesives and Bone graft substitutes, primarily at UU as Adj Prof, and also at EPFL in Lausanne, Switzerland. I am a Chartered Engineer (FIMechE, UK) and Chartered Scientist (FIPEM, UK) with a Diploma in Management and Marketing IMI Dublin (Ireland), a PhD in Biomedical Engineering, Strathclyde University, (Scotland) and a BTech. Mechanical Engineering, Brunel University London, (UK).

Speaker: Assoc. Prof. Karin Fromell, Dept. Immunology, Genetics and Pathology, UU.

Title: Innate immune response to biomaterials

Abstract:  Important for all types of biomaterial implants is their biocompatibility, which can be defined as “The ability of a material to perform with an appropriate host response in a specific application”. Many of the materials are far from ideal, which leads to unwanted adverse reactions triggered by the body's defense systems. The innate immune system is the first line of defense against microorganisms and foreign substances in the human body and extremely important for our survival. However, also biomaterials intended fulfill a function in the body, will be recognized as foreign by the innate immune system, which may lead to both thrombosis and inflammation. By understanding the mechanisms behind these adverse reactions, the possibilities of preventing them, or at least controlling them, increase. In this seminar I will present the models we have developed to be able to study the biocompatibility of different biomaterial in contact with blood and how to monitor activation and interaction between different components of innate immunity.

Bio: Karin Fromell is Associate Professor/Docent at the Department of Immunology, Genetics and Pathology at Uppsala university. Her area of expertize is the mechanisms behind activation of the cascade systems in blood and their cross-talk i.e. thromboinflammation, with focus on the effect of surface properties on key initiator proteins in the coagulation and complement systems. She has a PhD in Physical and Analytical Chemistry with a specialization in Surface Biotechnology followed by five years as Protein assay specialist at Modpro AB, which is a small biopharmaceutical company designing molecules for recognition of proteins.

Speaker: Petra Dittrich, ETH Zurich

Title: Droplet microfluidics as artificial cells

Bio: Petra is a Professor of bioanalytics in the Department of Biosystems Science and Engineering at ETHZ, Switzerland. Her research group develops miniaturized devices (so-​called lab-​on-chip technology or microfluidics) for applications in the life sciences using an interdisciplinary approach  combining chemical, physical, biological and engineering aspects of microfluidics-​based technology.

Learn more about Prof. Dittrich and the Bioanalytics Group on their homepage here.

Speaker: Professor Lorena Betancor, Department of Biotechnology, Faculty of Engineering, Universidad ORT Uruguay

Title: Biomimetic nanohybrids as nanoactuators for Enzyme Prodrug Therapy

Abstract: Nanohybrids harness the intrinsic characteristics of each individual material in a composite  that exhibits improved and new additional properties as a result of a synergetic effect of its structural builders. In this context, the synthesis of bio-nanohybrids based on biosilicification processes taking place in nature represents an extraordinary suitable approach compatible with enzyme immobilization due to its mild and fast synthetic approach (room temperature, neutral pH, free of organic solvents).

In this seminar I will we present a recently developed nanohybrid (nH) combining biomimetic silica (BioSi), magnetic nanoparticles (MNPs) and horseradish peroxidase enzyme (HRP), acting as core elements. The purpose of this nanocomposite is to combine the ability of MNPs to absorb energy in the presence of an external alternating magnetic field (AMF) and release it in the form of heat to locally reach the optimal HRP temperature via remote control. Triggering and modulation of the HRP activity may be used in Directed Enzyme Prodrug Therapy (DEPT) where a non-active prodrug is converted into a biologically active therapeutic molecule by enzyme activation. Details on the integration of each component of the nH will be discussed as well as its characterization and in vitro application in the remote enzyme activation.

Bio: Lorena Betancor is currently a Professor at the Department of Biotechnology at Universidad ORT Uruguay (Montevideo, Uruguay). Originally a Biochemist from Universidad de la República (Uruguay), she is a PhD from Universidad Autónoma de Madrid and has 4-year post-doc experience working first for the Oak Ridge Institute of Science and Education at the School of Civil and Environmental Engineer (Georgia Tech, Atlanta) and as a fellow of the Ministry of Science (Spain) at the Department of Biochemistry of the University of Cambridge (Cambridge, UK). She was also a research assistant at this University and a Ramón y Cajal fellow at Instituto Madrileño de Estudios Avanzados (Madrid, Spain) before returning to Uruguay. Her background lies in biocatalysis and enzyme immobilization with a particular focus in nanobiotechnology. She is the head of the Protein Technology group at ORT and is now focused on the use of biocatalysts immobilization for the development of environmentally friendly biocatalytic processes, biotechnological valorization of industrial byproducts, and biomedical applications.

Speaker: Assoc. Prof. Orcun Göksel, Department of Information Technology/MTSI, UU

Title: Deep Learning in Computer-assisted Diagnosis, Therapy, and Imaging

Abstract: This talk is aimed to serve as an overview of research interests in our group. With specific focus on combining imaging, image analysis, and learning systems, the talk will demonstrate several research topics and our recent developments therein; covering rather the breadth than the depth.  Several of our works revolve around ultrasound imaging, which is a safe, cost-effective, portable, and real-time imaging modality.  Its uses will be presented, for example, for elastography for characterizing shear-modulus and for speed-of-sound relating to bulk-modulus.  Several clinical applications, such as on biomechanical and imaging simulations for training and therapy, will also be exemplified.  An overarching theme throughout the talk will be our cutting-edge deep-learning solutions on the various research questions involved.

Bio: Orcun Goksel is associate professor at the Department of Information Technology at Uppsala University. He leads the research group Computer-assisted Applications in Medicine, as part of Uppsala Medtech Science and Innovation Centre and the Centre for Image Analysis. He received bachelor degrees in computer science and electrical engineering. Following a PhD degree from University of British Columbia, in Vancouver, Canada, he held a Swiss National Science Foundation Professorship at ETH Zurich, Switzerland, before joining Uppsala University. His research interests include machine learning, computer vision, ultrasound imaging in biomedical applications, biomechanical tissue characterization, image reconstruction, image-guided therapy, and patient-specific modelling and simulation. By devising novel imaging and image analysis techniques and developing them for clinical translation, his research efforts push the boundaries of diagnostic and surgical procedures as well as minimally-invasive interventions.