AME: Project Examples
Overview of project-examples of the AME-departments:
Projects of the department
CVE – Cardiovascular Engineering
3D-printed Membranes for Artificial Lungs
This project is part of the SPP 2014: Towards an Implantable Lung
German research foundation
Development and evaluation of minimally invasive techniques to connect an artificial lung to the heart and central vessels
This project is part of the SPP 2014: Towards an Implantable Lung
|German research foundation
Project number 347325614
Alternative to conventionally used cannula of Extracorporeal Lung Assist systems
This project is part of the SPP 2014: Towards an Implantable Lung
|German research foundation
Project number 346973239
|EduDerm||Development and evaluation of a realistic skin, vascular and tissue model from artificial materials for the training of basic surgical skills.||This research project is funded by the Program „Innovative Lehrprojekte“ of the Faculty of Medicine, RWTH Aachen|
|EndOxy||Development of a biohybrid artificial lung||Interdisciplinary Centre for Clinical Research within the faculty of Medicine at the RWTH Aachen University (T12-2)|
|Fontan Pro||An individual adaptable fontan-prosthesis in combination with a cardiac support system is a new and innovative therapeutic option for patients, which are born with only one functioning ventricle.||Federal ministry of education and research|
Ghostcells are red blood cells, known as erythrocytes, with a lower intracellular hemoglobin concentration. Hemoglobin is the reddish substance inside the cells. After applying a controlled lysis, the cells are loaded with calcium and a fluorescent indicator is added to the surrounding liquid. This setup allows for the measurement of the red blood cells destruction, also called hemolysis. With those measurements, the hemolysis can be quantified spatially for the first time.
|German Research Foundation
Project number STE 1680/12-1
In the context of the HOC-Surf project, we investigate the applicability of the plasmaelectrolytic oxidation treatment for manufacturing cost-efficient and particular hemocompatible ceramic surfaces under the conditions of a ventricular assist device.
|European Union and Land Nordrhein-Westfalen|
|Surface Structures||Improving the hemocompatibility of polyurethane by means of surface structuring||START-Program of the Faculty of Medicine, RWTH Aachen|
|OxyBench||Testbed for implantable Lungs||START-Program of the Faculty of Medicine, RWTH Aachen|
|Perinatal Life Support System||Supporting the safe development of extremely preterm born infants outside the womb by preserving the innate fetal cardiorespiratory physiology ex vivo||Horizon 2020|
|PLAAO||Personalized LAA occluder||
Federal ministry of education and research
|Polyvalve||Polymeric Prosthetic Heart Valve for Life||INTERREG Program V-A Euregio Maas-Rheine of the European Union
Grant Number 2016/98602
|ProtEmbo||Development and testing of a novel embolic protection device.||Federal ministry of education and research
Support code 13GW0058B
|PulmoStent (Part CVE)||Biohybrid stent for the treatment of airway stenoses||Federal Ministry of Education and Research
Support code 03VP03290
Projects of the Department
RPE – Rehabilitation and Prevention Engineering
PfleKoRo: Facilitated care for difficult-to-care patients through cooperative robotics
|autoPrätz||A technical assistance system for a patient-specific, autonomous rehabilitation therapy for musculoskeletal diseases with sensor-based feedback. Development under Consideration of usability, patient and therapist acceptance|
|i2-CoRT||Innovation and Implementation Accelerator for Complex Rehabiliation Technology|
Development of a smart orthotic device to improve Movement capacity of patients suffering from spasticity.
Development of new Materials and nanocomposites functional for a technological application and validation on a modular Prosthesis for upper extremity (DEMaPro)
Development of a robot-based rehabilitation system enabling individualized rehabilitation which can be performed autonomously by the patient.
|Dyneva||Examination of the effect of a dynamic flexion-orthosis on the activation of the low back muscles.|
|HSR-EMG||Non-invasive assessment of single motor unit activity enabling diagnosis of neuromuscular disorders free of pain.|
|Early diagnosis of movement disorders||Development of a non-invasive procedure which supports the objective and quantitative evaluation of the spontaneous motor activity of babies.|
|Movement Analysis of upper extremities||Development of methods and procedures to analyze freely performed movements of the upper extremities.|
|Gait Analysis||Development of novel methods to quantify the quality of gait.|
|Detection of limping||Development of an ambulatory system allowing to analyse quality of gait|
Projects of the Department
BEE – Biophysical & Education Engineering
|In the project MAD Control, a multifunctional platform for hybrid implants with magnetic nanoparticles in dual function will be developed: Sensing effect in magnetic imaging and active drug release by magnetic excitation.|
|In the ProNano 2.0 project, the performance and effectiveness of a polymer stent is being investigated, which contains nanoparticles that can be used to heat stent material to this temperature threshold in a controlled manner. As a result, tumor cells are specifically damaged and the stent has a "self-cleaning" effect in addition to its supportive function.|
|In NaFiDe, a method for future in vivo determination of the relevant implant properties (especially its degradation state) is established by means of in vitro measurements. In these measurements, magnetic nanoparticles inside the implants will be used as sensors in the magnetic field of a magnetic resonance imaging (MRI) device.|
Projectes of the Department
BioTex - Biohybrid & Medical Textiles
|TeXlastins||The project aims to translate the design principles found in nature to the laboratory, with the target mission of developing functional cardiovascular implants.|
|BioBased Value Cirle||The project aims to contribute to the development of a circular biobased economy by exploiting the potential of biobased materials.|
|EndOxy-InFlame||The influence of a biohybrid lung on inflammatory pathways and immune system endothelial cell interaction is investigated.|
|BioPacer||The project is developing a biological pacemaker for babies and children.Traditional pacemakers are too big for the chest.The "BioPacer" consists of a small cylinder that is populated with endogenous cells of the heart-sick child and cultivated in a bioreactor. It will treat heart rhythm disorders.|
|Fontan||The aim of the project is to improve the quality of life and prevent morbidity and mortality in patients in the Fontan circulation. This is to be achieved by generating an autologous, flap-bearing, contractile conduit in the sense of a subpulmonary neo-ventricle.|
|PulmoStent||Development a biohybrid stent for treatment of airway stenoses.|
Project of the Department
SCM – Science Management
|mi-mappa||A new integrative competence model of medical engineering based to be used with data mining algorithms has been conceptualized by the Department of Science Management.|
Update of the trend- and innovation monitoring, in short TIM, for the medical industry in North Rhine-Westphalia
Specialized consortia developed innovative systems and solutions for cardiovascular therapy. The individual adaptation of medical devices and systems to the pathological needs of patients have been implemented in seven R&D projects.
|More Projects: https://www.dwi.rwth-aachen.de/projekte|
DFG project "Towards a model based control of biohybrid implant maturation"
P1: BioInterface - Functional fibrin-based hydrogels for the direction of cell/biomaterial interactions in biohybrid cardiovascular Implants
Since decades, tissue engineering is a broad and interdisciplinary research field with its research activities focusing on future applications to replace diverse organs or tissues. However, although very promising biohybrid systems are developed for transplantations, a prediction on how tissue-engineered constructs behave in vivo after transplantation is not possible today.
In our subproject (P1) of the consortium, we will develop functional, molecular building blocks for the tailored design of fibrin-based hydrogels. We will then systematically investigate cell/biomaterial interactions with the focus on the long-term behavior in tissue engineering. Our data on the physico-chemical properties (chemical structure, mechanical properties, degradation profiles) of biomaterial substrates and their influence on the cell behavior will undergo bioinformatic analyses with the aim to predict long-term behavior of tissue-engineered constructs in cardiovascular therapies. These data contain (i) predictions on the cell behavior of endogenous recipient cells in contact to transplanted biohybrids or implants as well as (ii) predictions on the cell behavior within tissue-engineered constructs after transplantation.
We will synthesize novel biohybrid hydrogels consisting of fibrinogen and reactive, biocompatible N-Vinyllactam-based copolymers. These hydrogels will possess controllable mechanical properties, various morphologies and directed degradation behavior. The fibrin-based hydrogels will be investigated systematically in contact to diverse cell types related to the cardiovascular field, such as mesenchymal stem cells (MSC), smooth muscle cells (SMC) and endothelial cells (EC). The cells will be cultured either on the hydrogels or within the hydrogels. We will assess the basic compatibility of the hydrogels concerning cell adhesion, viability, proliferation, apoptosis, necrosis and cytotoxicity according to ISO 10993-5. In addition, we will analyze the influence of the hydrogel properties (elasticity, degradation) on the cell behavior with a focus on (i) stem cell differentiation (adipogenic, osteogenic, chondrogenic and in particular myogenic differentiation), (ii) matrix remodelling and (iii) vascularization. The gained data will be analyzed bioinformatically to predict the long-term behavior of cells in contact to hydrogels. Thus, we will provide data of our subproject as an important part for the implant-maturing model, which will be developed in P6.
Priv.-Doz. Dr. rer. nat. Sabine Neuss-Stein
Univ.-Prof. Dr. rer. nat. Andrij Pich
P2: Architissue - 3D-Architektur biohybrider kardiovaskulärer Implantate durch additive Fertigung
The production of biohybrid implants requires the combination of living cells and non-living scaffolds in a specific 3D arrangement to obtain tissues that recapitulate native ones in their composition and function. Ideally, the scaffold provides the overall geometry and structural stability and at the same time defines the 3D microenvironment with tailored properties to guide cellular growth and extracellular matrix synthesis. The scaffold design and the material properties affect the cell behavior in multiple ways, ultimately influencing the final tissue’s function.
The aim of this project is to investigate the influence of precisely defined 3D scaffold architectures on the maturation of functional biohybrid implants.
The project relies on the capability of additive manufacturing techniques to control the spatial distribution of pore size, shape and interconnectivity as well as mechanical and structural properties of polymeric scaffolds. In ArchiTissue, we will apply initiator-free laser polymerization of cytocompatible pre-polymers in combination with stereolithography (SL) to create a variety of microstructures as building blocks, which can be selectively assembled into 3D macro geometries.
The effect of the so obtained microarchitectures on cell behavior will be investigated with mono- and co-culture of smooth muscle cells and endothelial cells, in structures of increasing complexity. Indeed, the high degree of freedom associated with the fabrication technique allows creating scaffolds exhibiting non-homogeneous composition and anisotropic properties typical of native tissues.
Based on the results, the framework conditions for the development of a multi-layer, biohybrid heart valve will be determined. These conditions and parameters will be collected in a structural catalogue, which will serve as a general platform for biohybrid implants as well as input for a maturation model of such implants.
The three layers of a heart valve leaflet, the collagen-rich fibrosa, the glycosaminoglycan-rich spongiosa and the elastin-rich ventricularis, will be realized by the cell colonization of the scaffold in ad-hoc developed bioreactors. For this purpose, the mechanical properties and the microarchitecture are first tailored for each layer to influence the behavior of the endothelial and smooth muscle cells, especially with respect to the production of the extracellular matrix.
The following scientific questions will be addressed to achieve the project’s aim:
- Creation of 3D architectures by combination of micro- and macroscale structuring by combining multiphoton polymerization and SL
- Investigation of the interaction between 3D architecture and cells under static and dynamic cultivation in bioreactors
- Development of a multi-layered biomimetic biohybrid model for heart valve tissue engineering
Priv.-Doz. Dr. Petra Mela
Dr.-Ing. Arnold Gillner
Dr. rer. nat. Nadine Nottrodt
P3: TexValveModelling - Modelling of the structure and fluid-structure interaction of biohybrid heart valves on tissue maturation
The tissue maturation process is a crucial point during the production of biohybrid implants. A special focus must lie on the evolution of the extracellular matrix (ECM), which must be capable of bearing high oscillating pressure loads over a long period. In nature, this is achieved by an load oriented arrangement of collagen and elastin fibres within the tissue itself. Such fibre reinforce the tissue just like carbon fibre do with plastics. The growth process of such fibres strongly depends upon the loading and consequently on the stress state within the tissue itself. In biohybrid implants, this stress state is being altered by the inclusion of a polymeric reinforcement structure (scaffold). This leads to a need for computational models, which can predict the evolution of the ECM under the influence of a scaffold structure. The scope of this project is to develop a simulation framework, which is capable of predicting the tissues evolution within the bioreactor. To achieve this, a continuum mechanical material model is developed.
P4: ProcessModelling – Process-oriented matuaration model of biohybrid heart valves during bioreactor conditioning
The goal of this project is to develop process-oriented system analysis and modelling of the maturation process of biohybrid heart valve implants. These valves are conditioned in a bioreactor under pulsatile pressure and flow conditions. Focus of the proposal is the investigation of the relation between on the one hand the output variables y(t) and input variables u(t) of the process, and on the other hand the state variables x(t), describing the actual maturation status of the valve at a functional and a cellular level. Since the maturation process is key to the properties of the heart valve under development at any point in time, it is crucial to determine how these properties can be matched to both the initial values of the state variables of the pre-implant and the desired final values of the state variables at the end of the process. Output variables y(t) are physical and biochemical properties of the bioreactor medium, functional parameters describing opening and closing behaviour of the valve (obtained using ultrasound and photography), and data on the actual composition of the valve during development. The latter are obtained using Two-photon microscopy (2PM) of extracellular matrix formation (elastin and collagen) and of the interstitial and endothelial cells. The 2PM data will be obtained using an endoscopic microscope, necessary to observe the implant condition continuously in time. This avoids the need for histopathological characterization, since that would require interruption and disruption of the maturation process. Some of the state variables based on expertise, can be directly deduced from specific output parameters, resulting in pre-determined dependence matrices and characteristic diagrams. Based on the identified system dynamics and its mathematical description, we will construct a model of the maturation process. Ideally, model based state observation utilizing input and output variables will allow a continuous quantification of the state variables over time, which will obviate the need for destructive histological examinations. In this project, data for modelling and validation will be obtained experimentally, requesting explicit need for bioreactor experiments. Methodical aspects of this projects focus on applying the paradigm of object-oriented modelling and building a component library. Besides, another focus will be on modelling the maturation process as a spatially parametrically distributed system. On a more fundamental level, another goal of the project is to investigate how object-oriented modelling and its advantages can be transferred to parametrically distributed systems, which is not yet established. In phase II of this project, the maturation model will be used to construct a model-based control of the bioreactor. This expresses the ultimate goal to obtain a fully controlled individualized maturation process at cellular and tissue level of biocompatible and long-term durable heart valve implants.
Univ.-Prof. Dr. med. Dipl.-Ing. Thomas Schmitz-Rode
Univ.-Prof. Dr.-Ing. Dirk Abel
Prof. Marc van Zandvoort
P5: DurImplant – Analysis of implant behavior after bioreactor maturation in vitro
The aim of project P5 is the development of an in vitro methodology for the investigation of the durability of biohybrid implants with main focus on the propensity to calcification as a decisive limiting factor of the implant lifetime and function. The issue of calcification propensity and its prediction and prevention is already of great importance in avital bioprosthetic heart valves. This fact is countered by the hypothesis that biohybrid heart valve prostheses with a vital, functionally active endothelium are a natural barrier for calcification, which is to be investigated in a test environment that is as close to reality as possible. To test avital bioprosthetic heart valves, CVE already has a dynamic durability test system, which has hitherto been based on a purely mechanical and physicochemical basis, but does not offer a suitable test environment for cellularized material either from a physiological or cytotoxicological point of view. This aspect is to be addressed by the development of a biohybrid-compatible test system. Important parameters with regard to the test environment are the cell compatibility with simultaneous calcification potential of the fluid, physiological pH, temperature and flow conditions as well as the online detection of the formation and progression of calcifications. In addition to the test environment, many individual influencing factors, whose role in calcification have not yet been fully clarified, have to be taken into account (blood, inflammation, material and surface parameters, calcification inductors and inhibitors and cell involvement). These factors are to be investigated first in a miniaturized flow chamber system on material patches. A corresponding flow chamber is developed and built at CVE. The advantages of a miniaturized system for research purposes are: i) greater flexibility in the composition of various fluids and fluid-substrate combinations so that individual calcification parameters can be separately examined, ii) a constant fluid composition in the test chamber through an open flow system (single pass); and (iii) the possibility of parallel operation of several flow chambers with microscopic online tracking of the calcification process. Comparably small amounts of substrates allow the testing of different materials with and without living cells even before complex constructs (implants) are available. The Fetuin-A-based imaging, inflammatory reporter cell assays and (patho) -biomimetic fluids with high-molecular-weight mineral precursors developed at ZMG are used. The influence of surface structures and anomalies is to be investigated by means of optical coherence tomography of the starting materials and correlation with the calcification patterns occurring after testing.
Univ.-Prof. Dr. rer. nat. Wilhelm Jahnen-Dechent
Univ.-Prof. Dr.-Ing. Ulrich Steinseifer
Priv.-Doz. Dr.-Ing. Jutta Arens
P6: ImplantMonitoring – Multimodal imaging for longitudinal in vivo monitoring of Biohybrid implants
The tissue maturation of biohybrid implants continues even after implantation. This healing and remodeling process, which represents an interaction between the vital implant and its environment, is of central importance for the functionality and lifespan of biohybrid implants. The aim of the project is therefore to evaluate and develop methods that allow a longitudinal consideration of the biological dynamics of the insertion and remodelling process of biohybrid implants and their components. MR-PET imaging and molecular sonography will be used to measure interactions between (i) biomaterial, (ii) cellular components and (iii) implant environment in vivo. As the first geometrically simplified model structure, a biohybrid vascular prosthesis (I.D. 3 mm) is used, which is composed of (1) a fibrin-gel matrix as cell carrier structure for myofibroblasts, (2) a textile, partially biodegradable reinforcement as support structure, and (3) an endothelialized lumen. For longitudinal imaging, the textile support structures are provided with long-lived MRT markers. Iron oxide nanoparticles (USPIO) are used to mark the degradable part of the support structures and make it visible via means of 1H MRI. For the non-degradable part of the support structure fluorinated polymers (19F-TPU) are used and shown with 19F-MRT. The labeled biohybrid vascular prostheses are implanted in rat aorta to characterize the in vivo remodelling process. The biological processes of tissue/vascular remodelling are investigated using PET radiotracers, molecular MRI and sonography. Inflammatory reactions will be visualized by 18F-FDG PET measurements, cellular apoptosis and necrosis by 18F-Duramycin PET measurements. The cellularity of the vascular prostheses as well as the formation of a local tissue edema will be determined by diffusion-weighted MRI imaging and FLAIR sequences or T2 relaxometry. A molecular MRI probe against elastin will be used to investigate elastogenesis during the in vivo remodeling process. The obtained non-invasive data will be validated (immunologically) histologically.
In summary, the project provides important insights into the in vivo remodelling process of implants and their interactions with the recipient organism. The data serve as an essential basis for the maturation model to enable prediction of the in vivo implant behavior already during the manufacturing process. The technical design, cell source and biomaterial are identical to those of the biohybrid heart valve. In the second phase of the project, strategies will be developed to transfer the findings and technologies gained to the more complex geometric and moving form of the heart valve prosthesis.
Univ.-Prof. Dr. med. Stefan Jockenhövel
Univ.-Prof. Dr. med. Fabian Kießling