Project A02 investigates microscopic and macroscopic simulations in continuous media in context with the therapeutical electrical stimulation of bone, cartilage or deep brain structures.
Essential is the numerical solution of the relevant partial differential equations (Maxwell’s equations, etc.) with the finite element method to determine the desired quantities, particularly the electric field distribution. For the electrical parameters of the biological tissues, primarily parameterized relaxation models are employed. As already started on a pilot basis in the first funding period of the Collaborative Research Centre, values from project A05 can be used in the project. Electrical and electrochemical effects at the electrode-tissue interface, which depend on the selected type of stimulation, are employed through equivalent circuit models. In the first funding period, suitable theoretical and numerical models were selected. They will be further extended or refined. Results from simulations on a smaller scale are incorporated via homogenization approaches, equivalent circuit models or parameter extraction. Besides extending the multiscale and multiphysical models, establishing stochastic and inverse methods for determining patient-specific optimized recommendations for stimulation parameters presents another focus for the second funding period. To this end, an open-source,  multipurpose simulation platform based on the tissue-specific solutions established in the first funding period will be created. The clinical researchers in the consortium will test the simulation platform utilizing easy-to-use graphical user interfaces.

Project duration: 01.07.2021 to 30.06.2025

Principal Investigators: Prof. Dr. Ursula van Rienen, Dr.-Ing. Revathi Appali

Team involved: M.Sc. Jan Philipp Payonk, M.Sc. Lam Vien Che,  Dr. Anna Karina Fontes Gomes

Bioreactors are used increasingly in bone tissue engineering approaches, but the existing homogenous niche applied is generally insufficient to achieve/support formation of bone-like constructs. In physiology, multiple osteochondral cells are present in high cell density and their dynamic interactions are critical for bone development and regeneration processes. This is also complemented with supporting parameters such as oxygen tension (pO2) distribution, biochemical stimuli, and physical/mechanical stimuli to establish the dynamic niches essential for the growth of naïve organs (i.e. cartilage and bone) and attaining their functionalities. In this proposal, we aim to investigate the synergistic potentials of 5 distinct parameters to recapitulate bone developmental processes in a perfusion bioreactor. Through the established dynamic biomimetic niches, the effects on construct development and capability to achieve bone-like tissues in vitro will be assessed. These parameters include 1) medium pH; 2) pO2; 3) Young´s modulus of 3D-printed scaffolds; 4) multi-step osteochondral differentiation regimes and 5) Transformer-like induced electric field (TLC-EF) stimulation to emulate piezoelectric stimuli during movement. Human bone marrow-derived mesenchymal stem cells (hMSC) and human induced pluripotent stem cells (hiPSC) will be used to define the proficiency of biomimetic niches. Their potential to derive different osteochondral cell-types in the biomimetic niches will be critically assessed. Specifically for TLC-EF stimulations, multiscale modelling/simulations that describe EF/Bone construct interactions and the effects on osteogenesis will be combined with experimental validations. This is done with the aim to define an effective range of EF parameters for bone tissue engineering applications. Ultimately, this study will result in a specific set of conditions/stimuli that can recapitulate physiological-like niches in vitro. The approaches applied will also introduce a novel concept to the field of tissue engineering and can be further exploited to derive bone-like constructs with near-physiological properties in a bioreactor.

Project duration: 3 Years (from 07/2021)

Principal Investigators: Prof. Dr. Ursula van Rienen, Dr.-Ing. Poh Soo Lee, Dr.-Ing. Benjamin Kruppke

Team involved: Post-doctoral researcher (Uni Rostock), Dr.-Ing. Revathi Appali

TU Dresden: Dr.-Ing. Poh Soo Lee (Eigene Stelle), PhD Student: Dipl.-Ing. Franziska Alt – supervised by Dr.-Ing. Benjamin Kruppke

This project aims at understanding the effects of demyelination and remyelination in Multiple Sclerosis through a trans-synaptic modelling approach. We use neuroVIISAS (https://neuroviisas.med.uni-rostock.de/neuroviisas.shtml) developed by Prof. Dr. Oliver Schmitt to carry out this study. neuroVIISAS (neuro Visualization, Imagemapping, Information System for Analysis and Simulation) is an open framework for integrative data analysis, visualization and population simulations.

Project duration: 2019 – 2021

Supervisors: Prof. Dr. Ursula van Rienen, Prof. Dr. Oliver Schmitt, Dr.-Ing. Revathi Appali

State Graduate Fund Holder: M.Sc. Vishnu Prathapan

Sensorineural deafness is caused by the loss of peripheral neural input to the auditory nerve, resulting from peripheral neural degeneration and/or a loss of inner hair cells. Provided spiral ganglion cells and their central processes are patent, cochlear implants can be used to electrically stimulate the auditory nerve to facilitate hearing in the deaf or severely hard-of-hearing. Neural degeneration is a crucial impediment to the operational success of a cochlear implant. The present, first-of-its-kind two-dimensional finite-element model investigates how the depletion of neural tissues might alter the electrically induced transmembrane potential of spiral ganglion neurons. The study suggests that even as little as 10% of neural tissue degeneration could lead to a disproportionate change in the stimulation profile of the auditory nerve. This result implies that apart from encapsulation layer formation around the cochlear implant electrode, tissue degeneration could also be an essential reason for the apparent inconsistencies in the functionality of cochlear implants.

Team Lead: Prof. Dr. Ursula van Rienen

Team involved: Dr.-Ing. Kiran Sriperumbudur, Dr.-Ing. Revathi Appali