Dr. Silvia Budday

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.

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.