Prof. Dr.-Ing. Silvia Budday

• Mechanics-augmented brain surgery

  (Third Party Funds Single)

  Project leader: Silvia Budday
  Term: 1. October 2024 - 30. September 2029
  Acronym: MAGERY
  Funding source: ERC Starting Grant
  URL: https://www.lkm.tf.fau.eu/
  Abstract

  This project aims at revolutionising the treatment of brain disorders through mechanics-augmented brain surgery (MAGERY). Due to the ultrasoft nature of brain tissue, surgical procedures have exceptionally high requirements for minimal invasiveness and maximal safety. During the procedure, brain tissue largely deforms and is easily loaded beyond its functional tolerance. A promising technology to improve surgical outcomes is to integrate virtual information either through immersed virtual reality (VR) in training and planning or through augmented reality (AR) overlaying virtual information with the surgeon’s real view. Despite rapid advances, to date, most VR/AR solutions have disregarded the complex region-dependent mechanical properties of brain tissue and mechanics-induced cell dysfunction or death.

  The MAGERY project will follow a new paradigm by focusing on brain mechanics. We imply that we can minimise unnecessary brain tissue damage by integrating continuum mechanics-based simulations into VR/AR solutions. Realising this objective will require to combine state-of-the-art approaches in live cell imaging, nonlinear continuum mechanics, and computational engineering. The applicant and the MAGERY team will for the first time perform simultaneous large-strain mechanical measurements and multiphoton microscopy, and, through modelling and simulations, identify thresholds for tissue and cell damage under complex three-dimensional loadings. By merging simulation results and VR/AR techniques, this project strives towards real-time predictions of brain tissue deformation and corresponding damage. With her pioneering role in testing and modelling the complex behaviour of human brain tissue, the applicant has excellent prerequisites to tackle these challenges.

  If successful, this project can not only revolutionise VR/AR for brain surgery, but also leverage our understanding of the cellular response to three-dimensional mechanical loading across length and time scales.

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• Exploring Brain Mechanics (EBM): Understanding, engineering and exploiting mechanical properties and signals in central nervous system development, physiology and pathology

  (Third Party Funds Group – Overall project)

  Project leader: Paul Steinmann
  Term: 1. January 2023 - 31. December 2026
  Acronym: SFB 1540 - EBM
  Funding source: DFG / Sonderforschungsbereich / Transregio (SFB / TRR)
  URL: https://www.crc1540-ebm.research.fau.eu/
  Abstract

  Thecentral nervous system (CNS) is our most complex organ system. Despite tremendousprogress in our understanding of the biochemical, electrical, and geneticregulation of CNS functioning and malfunctioning, many fundamental processesand diseases are still not fully understood. For example, axon growth patterns inthe developing brain can currently not be well-predicted based solely on thechemical landscape that neurons encounter, several CNS-related diseases cannotbe precisely diagnosed in living patients, and neuronal regeneration can stillnot be promoted after spinal cord injuries.

  Duringmany developmental and pathological processes, neurons and glial cells aremotile. Fundamentally, motion is drivenby forces. Hence, CNS cells mechanicallyinteract with their surrounding tissue. They adhere to neighbouring cells and extracellular matrix using celladhesion molecules, which provide friction, and generate forces usingcytoskeletal proteins.  These forces aretransmitted to the outside world not only to locomote but also to probe themechanical properties of the environment, which has a long overseen huge impacton cell function.

  Onlyrecently, groups of several project leaders in this consortium, and a few other groupsworldwide, have discovered an important contribution of mechanical signalsto regulating CNS cell function. For example, they showed that brain tissuemechanics instructs axon growth and pathfinding in vivo, that mechanicalforces play an important role for cortical folding in the developing humanbrain, that the lack of remyelination in the aged brain is due to an increasein brain stiffness in vivo, and that many neurodegenerative diseases areaccompanied by changes in brain and spinal cord mechanics. These first insights strongly suggest thatmechanics contributes to many other aspects of CNS functioning, and it islikely that chemical and mechanical signals intensely interact at the cellularand tissue levels to regulate many diverse cellular processes.

  The CRC 1540 EBM synergises the expertise of engineers, physicists,biologists, medical researchers, and clinicians in Erlangen to explore mechanicsas an important yet missing puzzle stone in our understanding of CNSdevelopment, homeostasis, and pathology. Our strongly multidisciplinary teamwith unique expertise in CNS mechanics integrates advanced invivo, in vitro, and in silico techniques across time(development, ageing, injury/disease) and length (cell, tissue, organ) scalesto uncover how mechanical forces and mechanical cell and tissue properties,such as stiffness and viscosity, affect CNS function. We especially focus on(A) cerebral, (B) spinal, and (C) cellular mechanics. Invivo and in vitro studies provide a basic understanding ofmechanics-regulated biological and biomedical processes in different regions ofthe CNS. In addition, they help identify key mechano-chemical factors forinclusion in in silico models and provide data for model calibration andvalidation. In silico models, in turn, allow us to test hypotheses without the need of excessive or even inaccessibleexperiments. In addition, they enable the transfer and comparison of mechanics data and findingsacross species and scales. They also empower us to optimise processparameters for the development of in vitro brain tissue-like matricesand in vivo manipulation of mechanical signals, and, eventually, pavethe way for personalised clinical predictions.

  Insummary, we exploit mechanics-based approaches to advance ourunderstanding of CNS function and to provide the foundation for futureimprovement of diagnosis and treatment of neurological disorders.

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• Modellierung und Simulation der Regeneration von Rückenmarksgewebe (B01)

  (Third Party Funds Group – Sub project)

  Overall project: SFB 1540: Erforschung der Mechanik des Gehirns (EBM): Verständnis, Engineering und Nutzung mechanischer Eigenschaften und Signale in der Entwicklung, Physiologie und Pathologie des zentralen Nervensystems
  Project leader: Silvia Budday, Paul Steinmann
  Term: 1. January 2023 - 31. December 2026
  Acronym: SFB 1540 B01
  Funding source: DFG / Sonderforschungsbereich (SFB)
  Abstract

  B01 zielt auf die kontinuumsbasierte Simulation der Regeneration von Rückenmarksgewebe nach Verletzungen oder Krankheiten ab. Die Modellierung und Simulation wird die zeitliche und räumliche Entwicklung von Wachstums-, Umbau- und Heilungsprozessen erfassen. Wir werden uns insbesondere auf mechanisch bedingte Prozesse konzentrieren, die an der Regeneration des Rückenmarks nach traumatischen Verletzungen und bei Multipler Sklerose beteiligt sind. Um die konstitutiven Modelle zu kalibrieren, werden wir mechanische Tests an menschlichem und tierischem Rückenmarksgewebe nutzen.

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• Modellierung und Simulation von Fehlbildungen des Gehirns (A01)

  (Third Party Funds Group – Sub project)

  Overall project: SFB 1540: Erforschung der Mechanik des Gehirns (EBM): Verständnis, Engineering und Nutzung mechanischer Eigenschaften und Signale in der Entwicklung, Physiologie und Pathologie des zentralen Nervensystems
  Project leader: Silvia Budday
  Term: 1. January 2023 - 31. December 2026
  Acronym: SFB 1540 A01
  Funding source: DFG / Sonderforschungsbereich (SFB)
  Abstract

  A01 zielt darauf ab, ein Computermodell zu entwickeln, das die Mechanismen der abnormalen Gehirnentwicklung vorhersagt und die Diagnose und Behandlung von neurologischen Erkrankungen wie Epilepsie unterstützt. Basierend auf Erkenntnissen über das Zusammenspiel von Mechanik, Zellmigration, Zelldifferenzierung und Fehlbildungen des Gehirns aus den Projekten A02 bis A05 wird ein Mehrfeldmodell zur Vorhersage der physiologischen und pathologischen Gehirnentwicklung etabliert. Für die Modellkalibrierung und -validierung werden Datensätze aus dem Projekt A02 und mechanische Tests an bei chirurgischen Eingriffen entnommenen Hirngewebeproben verwendet.

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• Biofabrizierte Gradienten für funktionale Ersatzgewebe (B09*)

  (Third Party Funds Group – Sub project)

  Overall project: TRR 225: Von den Grundlagen der Biofabrikation zu funktionalen Gewebemodellen
  Project leader: Silvia Budday
  Term: since 1. January 2022
  Acronym: SFB/TRR 225 Biofab B09
  Funding source: DFG / Sonderforschungsbereich / Transregio (SFB / TRR)
  URL: https://trr225biofab.de/project-b09/
  Abstract

  Ziel dieses Projekts ist es, eine Plattformtechnologie zu entwickeln, um in Raum und Zeit klar definierte und reproduzierbare Gradienten herzustellen, diese zu analysieren und in silico zu modellieren, um ihre Auswirkung auf Zell-Biomaterial-Interaktionen untersuchen zu können. Hierfür sollen zunächst Druckköpfe entwickelt werden, mit denen sich kontrolliert Übergänge von Materialien aus den A-/B-Projekten, Wirkstoffen und Zellen erzeugen lassen. Durch die umfassende Charakterisierung der gedruckten Gradienten mithilfe mechanischer Testmethoden in Kombination mit bildgebenden Verfahren wird das Ergebnis bezüglich der Anforderungen der C-Projekte stetig analysiert und verbessert. Zusätzlich werden kontinuumsmechanische Modellierung und Simulation gezielt eingesetzt, um Prozessparameter, das Druckmuster und die 3D-Anordung im Konstrukt zu optimieren.

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• Experimente, Modellierung und Computersimulationen zur Charakterisierung des porösen und viskosen Verhaltens von menschlichen Gehirngewebe

  (Third Party Funds Single)

  Project leader: Paul Steinmann
  Term: 1. July 2021 - 30. April 2024
  Funding source: DFG-Einzelförderung / Sachbeihilfe (EIN-SBH)
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• Experiments, modelling and computational simulations to characterize the porous and viscous behaviour of human brain tissue

  (Third Party Funds Single)

  Project leader: Silvia Budday, Paul Steinmann
  Term: 1. July 2021 - 30. April 2024
  Funding source: DFG-Einzelförderung / Sachbeihilfe (EIN-SBH)
  Abstract

  Computational modelling in biomechanics can provide important insights into the underlying mechanisms of cerebral pathologies that go far beyond the possibilities of traditional methods. The improvement of current prevention and treatment strategies via numerical simulation can only be achieved with a realistic biomechanical model for brain tissue. Understanding and characterizing its short- and long-term biomechanical response, and linking it to its underlying microstructure is essential to develop reliable models. We aim to characterize the mechanical response of brain tissue via the development of a biphasic constitutive model based on a comprehensive set of experimental data. To achieve this goal, the work program is divided into four specific aims: (1) We will devise new experimental set-ups to adequately characterize the visco-porous nature of brain tissue under arbitrary loading conditions. There are very few published studies characterizing the porous effects in brain tissue, all restricted to a single loading mode. Yet, we need to to fit multiple loading conditions simultaneously for the identified model parameters to produce accurate computational results. (2) We will elucidate the relation between the macroscopic mechanical response and the tissue microstructure through microstructural investigations of the tested samples, and, potentially, identify structural model parameters. These investigations are key to confirming our assumptions that porous and viscous phenomena observed in experiments are intrinsically linked to the tissue components, and the interconnectivity of cells. (3) We will develop a poro-viscoelastic model to capture, at the continuum level, the individual effects of the fluid and solid components, and their interaction. The experimental findings in (1) and the structural parameters identified in (2) will enable us to replace phenomenological constitutive equations, previously used to describebrain tissue behaviour, with comprehensive microstructurally motivated material laws. A robust finite element framework will allow for the successful implementation of the proposed model. (4) We will accurately calibrate the model parameters through an inverse material parameter identification scheme and evaluate their physical meaning considering the observed porous and viscous phenomena. The outcome of the project will be a better understanding of the role porous and viscous effects have in the response of brain tissue to mechanical loading. We will have linked the miscrostructure of the tissue to its macroscopic behaviour via experimental and computational investigations. With the resulting calibrated model, we will further explore how structure and mechanical response are linked, as well as demonstrate the potential for application of the proposed model in clinically-relevant problems.

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• BRAIn mechaNIcs ACross Scales: Linking microstructure, mechanics and pathology

  (Third Party Funds Single)

  Project leader: Silvia Budday
  Term: 1. October 2019 - 30. September 2025
  Acronym: BRAINIACS
  Funding source: DFG-Einzelförderung / Emmy-Noether-Programm (EIN-ENP)
  URL: https://www.brainiacs.forschung.fau.de/
  Abstract

  The current research project aims to develop microstructurallymotivated mechanical models for brain tissue that facilitate early diagnosticsof neurodevelopmental or neurodegenerative diseases and enable the developmentof novel treatment strategies. In a first step, we will experimentallycharacterize the behavior of brain tissue across scales by using versatiletesting techniques on the same sample. Through an accompanying microstructuralanalysis of both cellular and extra-cellular components, we will evaluate thecomplex interplay of brain structure, mechanics and function. We will alsoexperimentally investigate dynamic changes in tissue properties duringdevelopment and disease, due to changes in the mechanical environment of cells (mechanosensing),or external loading. Based on the simultaneous analysis of experimental andmicrostructural data, we will develop microstructurally motivated constitutive lawsfor the regionally varying mechanical behavior of brain tissue. In addition, wewill develop evolution laws that predict remodeling processes duringdevelopment, homeostasis, and disease. Through the implementation within afinite element framework, we will simulate the behavior of brain tissue underphysiological and pathological conditions. We will predict how known biologicalprocesses on the cellular scale, such as changes in the tissue’smicrostructure, translate into morphological changes on the macroscopic scale,which are easily detectable through modern imaging techniques. We will analyzeprogression of disease or mechanically-induced loss of brain function. The novelexperimental procedures on the borderline of mechanics and biology, togetherwith comprehensive theoretical and computational models, will form thecornerstone for predictive simulations that improve early diagnostics of pathologicalconditions, advance medical treatment strategies, and reduce the necessity ofanimal and human tissue experimentation. The established methodology will furtheropen new pathways in the biofabrication of artificial organs.

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• Novel Biopolymer Hydrogels for Understanding Complex Soft Tissue Biomechanics

  (FAU Funds)

  Project leader: Paul Steinmann
  Term: 1. April 2019 - 31. March 2022
  URL: https://www.biohydrogels.forschung.fau.de/
  Abstract

  Biological tissues such as blood vessels, skin, cartilage or nervous tissue provide vital functionality
  to living organisms. Novel computational simulations of these tissues can provide insights
  into their biomechanics during injury and disease that go far beyond traditional approaches. This
  is of ever increasing importance in industrial and medical applications as numerical models will
  enable early diagnostics of diseases, detailed planning and optimization of surgical procedures,
  and not least will reduce the necessity of animal and human experimentation. However, the extreme
  compliance of these, from a mechanical perspective, particular soft tissues stretches conventional
  modeling and testing approaches to their limits. Furthermore, the diverse microstructure
  has, to date, hindered their systematic mechanical characterization. In this project, we will, as a
  novel perspective, categorize biological tissues according to their mechanical behavior and identify
  biofabricated proxy (substitute) materials with similar properties to reduce challenges related
  to experimental characterization of living tissues. We will further develop appropriate mathematical
  models that allow us to computationally predict the tissue response based on these proxy
  materials. Collectively, we will provide a catalogue of biopolymeric proxy materials for different
  soft tissues with corresponding modeling approaches. As a prospect, this will significantly facilitate
  the choice of appropriate materials for 3D biofabrication of artificial organs, as well as modeling
  approaches for predictive simulations. These form the cornerstone of advanced medical
  treatment strategies and engineering design processes, leveraging virtual prototyping.

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• Multiscale modeling of nervous tissue: comprehensively linking microstructure, pathology, and mechanics

  (FAU Funds)

  Project leader: Silvia Budday
  Term: 1. July 2018 - 30. June 2019
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• Modeling and computation of growth in soft biological matter

  (Third Party Funds Single)

  Project leader: Paul Steinmann
  Term: 1. February 2014 - 30. June 2020
  Funding source: DFG-Einzelförderung / Sachbeihilfe (EIN-SBH)
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Laboratory Training Biomechanics

since 2023

Biomechanics

2018 – 2023

Linear Continuum Mechanics

Winter term 2019/2020

Introduction to Neuromechanics

Summer terms 2016 and 2019