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ELAINE Lecture Series

Schedule of ELAINE Colloquia

Mon, 09.10.17: Dr. Tofail Syed, University of Limerick, Piezoelectricity in biological building blocks and potential physiological relevance

Abstract: 

Piezoelectric materials produces electricity when deformed and vice versa. Hierarchical biological structures such as bone, tendon, wood and silk have been known to show weak piezoelectricity when compared to technical piezoelectric polymers and ceramics. Their physiological significance is still a matter of speculation. Synthetic polypeptides have recently shown significant piezoelectricity to merit their use in technical applications. Our group has successfully predicted and quantitatively measured piezoelectricity in synthetic bone mineral hydroxyapatite and globular protein lysozyme and amino acids. In this colloquium we will discuss fundamental principles of piezoelectricity and emphasise the need for considering fundamental building blocks to understand physiological significance of piezoelectricity.

Wed, 25.10.17: Prof. Dr. Sascha Spors, University of Rostock, Open Science

Abstract: The reproducibility of results is one of the main principles of the scientific method. The irreproducibility of a wide range of scientific results has recently drawn significant attention. Besides problems in the research methods themselves, results were often not reproducible since necessary supplementary material as protocols, data and implementations were not available. Another issue is the lacking availability of data for further research by third parties. In many cases only the published results are available to other researchers. Open Science focuses on the ease of access and reproducibility of scientific results. This contribution introduces the concept of reproducibility and addresses common concerns. Best practices for Open Science in acoustics research are discussed and illustrated at examples.

Thu, 25.01.18: Dr. Lehner, TÜV SÜD Product Service, Rahmenbedingungen für die Zulassung ... (klick for details)

Thu, 25.01.18: Dr. Lehner, TÜV SÜD Product Service, Rahmenbedingungen für die Zulassung von Medizinprodukten im Zuge der neuen Medizinprodukteverordnung (MDR)

Abstract: Nach der Bekanntmachung der neuen amtlichen Fassung der Europäischen Medizinprodukte-Verordnung (Medical Device Regulation, MDR) am 05. Mai 2017 im EU-Amtsblatt trat diese am 25. Mai 2017 endgültig in Kraft. Die MDR ersetzt die beiden bestehenden Richtlinien MDD 93/42/EWG über Medizinprodukte (Medical Device Directive) sowie AIMD 90/385/EWG über aktive implantierbare Medizinprodukte (Active Implantable Medical Devices) und ist nach einer dreijährigen Übergangszeit ab dem 26. Mai 2020 verpflichtend anzuwenden.

Mit der Einführung der MDR werden die Anforderungen an den Inhalt der Technischen Dokumentation zukünftig deutlich detaillierter geregelt, auch ist der Inhalt von den Herstellern kontinuierlich zu aktualisieren. Beispielweise erhält jedes Medizinprodukt zur vereinfachten Rückverfolgbarkeit in Zukunft eine eindeutige Produktidentifizierungsnummer (UDI). Auch die Klassifizierung einiger Produkte ändert sich. So müssen eine Reihe von Implantaten, die bisher in Klasse IIb eingestuft waren, nun die Anforderungen von Klasse III Produkten erfüllen. Die MDR erfordert zudem eine strengere klinische Überwachung nach dem Inverkehrbringen der Medizinprodukte.

Wed, 28.02.18: Prof. Ma Ángeles Pérez Ansón, Zaragoza, Spain, Mechanobiology and Multiscale Modeling of Cell Proliferation and Migration

Multiscale modeling of bone mechanobiology: from cell proliferation and migration to bone remodeling simulations

María Angeles Pérez

M2BE-Multiscale in Mechanical and Biological Engineering, Aragon Institute for Engineering Research – I3A, Aragón Institute of Health Sciences –IACS, University of Zaragoza, Zaragoza, Spain

(angeles@unizar.es)

Skeletal mechanobiology aims to discover how mechanical forces modulate morphological and structural fitness of the skeletal tissues – bone, cartilage, ligament and tendon [1]. Mechanobiological models have been used to explain mechanoregulation in fracture healing, callus growth, distraction osteogeneis, bone ingrowth into porous implants and tissue engineering. The proliferation/migration of cells has been modelled by considering it to be analogous to diffusion. However, using a diffusion model to simulate cell dispersal means that proliferation and migration tend to create a smooth variation in cell density, but such a constraint is not physiological nor is it necessary if a more general random-walk model is used. Furthermore, random-walk models can simulate not only a preferred direction to migration but proliferation can also be explicitly modelled by multiplying cell numbers during dispersal, or several cell populations could be included simultaneously [2]. A random-walk model was also used to simulate proliferation, migration and differentiation of adult muscle satellite cells [3]. The model was validated with an invitro cell culture. Additionally, several examples where the random-walk model were used (mechanobiological simulations of tissue differentiation and cement infiltration within open-cell structures resembling osteoporotic bone) will be presented in this lecture.

In bone mechanobiology, bone cells respond directly or indirectly to the local strains engendered in their neighbourhood by external loading activity [4]. This process is named bone remodeling, which is the continuous turnover of bone matrix and mineral by bone resorption and formation in the adult skeleton. The mechanical environment plays an essential role in the regulation of bone remodeling in intact bone and during bone repair. During decades, a great number of numerically implemented mathematical laws have been proposed, but most of them present different problems and stability, convergence or dependence of the initial conditions [5]. Therefore, bone remodelling challenges, problematic and their applicability will be also presented in this lecture from a macroscale point of view.

Summarizing, previous computational models range from microscale to macroscale approaches. The development of a multiscale procedure can be used to deeply understand the mechanisms involved in bone mechanoregulation and/or bone diseases as osteoporosis.

REFERENCES

[1] Van der Meulen and Huiskes (2002). J Biomech, 35: 401-414

[2] Pérez and Prendergast (2007). J Biomech, 40: 2244-2253

[3] Garijo et al. (2012). J Theor Biol, 314: 1-9

[4] Mellon and Tanner (2012). Int Mater Rev 57: 235-255

[5] Garijo et al. (2014). Comput Methods Appl Mech Engrg, 271: 253-268

Fri, 16.03.18: Prof. Dr. Lars Timmermann, Marburg & Prof. Dr. Gerd Kempermann, Dresden, DBS and adult neurogenesis (klick for details)

16.3.2018: Prof. Dr. Lars Timmermann, Marburg and Prof. Dr. Gerd Kempermann, Dresden – DBS and adult neurogenesis - CRC 1270 ELAINE supported session as part of the 2018 Scientific meeting of the MDS Non-Motor PD Study Group; Universitätsplatz 1, free meeting registration for CRC members through the IRTG office, see https://ctnr.med.uni-rostock.de/parkinson2018-rostock/

Wed, 25.04.18: Prof. Dr. Dieter Scharnweber, TU Dresden, Some like it sweet - from protein/glycosaminoglycan interaction to functional biomaterials

Some like it sweet – from protein/glycosaminoglycan interactions to functional biomaterials

Dieter Scharnweber

TU Dresden, Institute of Materials Science, Max Bergmann Center of Biomaterials

INTRODUCTION

Numerous biological processes such as tissue formation, remodeling and healing are strongly influenced by the composition and the biochemical properties of the cellular microenvironment. Glycosaminoglycans (GAGs), as major component of the native extracellular matrix (ECM) can be chemically functionalized and thereby modified in their binding profiles, both for direct cell inter-action and for interaction with mediator proteins (e.g. growth factors). Thus GAGs and their derivatives are promising candidates for the design of functional biomaterials to control healing processes in healthy and health-compromised patients.

The lecture will present multidisciplinary studies aiming to improve our understanding on structure property relationships of GAG derivatives in their interaction with biological mediator proteins as well as on the biological effects of these interactions. This will be discussed exemplarily for key signaling molecules of healing processes in bone and skin.

Prominent effects are (i) anti-inflammatory, immunomodulatory properties towards macro¬pha¬ges/ dendritic cells, (ii) enhanced osteogenic differentiation of human mesenchymal stromal cells, (iii) al-tered differentiation of fibroblasts to myofibroblasts, (iv) reduced osteoclast activity and (v) im¬pro-ved osseointegration of dental implants in minipigs.

The resulting knowledge enables the consortium of our Transregio 67 for an advanced design of functional biomaterials to selectively control and promote healing processes as will be shown for bone and skin regeneration.

Wed, 27.06.18: Prof. Dr. Volker Mehrmann, TU Berlin, Modelling, Simulation and Control of Constrained Multi-Physics Systems (klick for details)

Prof. Dr. Volker Mehrmann, TU Berlin, Modelling, Simulation and Control of Constrained Multi-Physics Systems

Modelling, Simulation and Control of Constrained Multi-Physics Systems

Motivated from modeling modern energy transport networks, in particular those arising in coupling different physical domains, the energy based modeling framework of port-Hamiltonian systems is discussed. The classical port-Hamiltonian approach is systematically extended to constrained dynamical systems (partial-differential-algebraic equations). A new algebraically and geometrically defined system structure is derived, which has many nice mathematical properties. It is shown that this structure is invariant under Galerkin projections, changes of basis, and that a dissipation inequality holds. If such a system is controllable and observable then it is automatically stable and passive. Furthermore, the new representation is very robust to perturbations in the system structure. The advantages and the success of the new framework is illustrated by examples from gas transport, synchronization of power systems and the development of a new turbine.

We also discuss open problems associated with the new model approach. These include the adequate choice of time-integration methods that guarantee the dissipation inequality, the generation of such systems from pure input-output data, as well as good model reduction and optimal control techniques that make optimal use of the structure.

Wed, 25.07.18: Dr. Ilja Klebanov, Zuse Institute Berlin, Simultaneous parameter estimation for many patients (klick for details)

Dr. Ilja Klebanov, Zuse Institute Berlin

Simultaneous parameter estimation for many patients

In systems medicine, we are often faced with parametrized models, where the patient-specific parameters have to be inferred from large data sets involving many patients. The natural approach would be to consider each patient separately, however, a lot of information can be gained by analyzing the data set as a whole. This concept of 'borrowing information' is the essence of so-called empirical Bayes methods, which build up an informative prior from the data before performing individual Bayesian inference for each patient. Guided by a simple example, we will discuss how this can be accomplished in a consistent way.

Wed, 22.08.18: Prof. Dr. Thomas Heimburg, Niels Bohr Institute University of Copenhagen, The excitability of nerves .. (klick for details)

Prof. Dr. Thomas Heimburg, Niels Bohr Institute University of Copenhagen

The excitability of nerves and the role of anesthetics 

It is a central paradigm in biology that excitatory events in cells are of purely electrical nature. The nervous impulse is attributed to the electrical activity of a class of proteins called voltage-gated ion channels. However, it is widely unknown that during the nerve pulse also the temperature, the thickness and the length of nerves change, i.e., properties that do not manifest themselves on the molecular scale. Furthermore, in contrast to expectations one finds no dissipation of energy in experiments on nerves. Many properties of nerve pulses rather resemble those of sound or solitons, respectively. Solitons are sound-pulses that travel without changes in shape and without dissipation of energy. The electrical pulses in classical electrophysiology and electromechanical solitons differ largely in their physical implications.

In this presentation we show that in the electromechanical approach, the excitability of the nerve membrane can be compared to the free energy difference between the liquid and the solid phase of the biomembrane. Anesthetics change this free energy difference due to melting point depression. This reduces the excitability of the nerve membrane and leads to an increase in stimulation threshold. We compare the theoretical experiment with the outcome of clinical experiments on the human median nerve and other nerve systems. We demonstrate that the electromechanical theory is able to provide a good understanding for anesthesia and its effect on nerve excitability.