Liesbet Geris (DOB 04.06.1979) is Professor in Biomechanics and Computational Tissue Engineering at the Department of Aerospace and Mechanical Engineering at the university of Liège and Associate Professor at the Department of Mechanical Engineering of the KU Leuven, Belgium. From the KU Leuven, she received her MSc degree in Mechanical Engineering in 2002 and her PhD degree in Engineering in 2007, both summa cum laude. In 2007 she worked as a postdoctoral researcher at the Centre of Mathematical Biology of Oxford University.
Her research interests encompass the mathematical modeling of bone regeneration during fracture healing, implant osseointegration and tissue engineering applications. The phenomena described in these mathematical models reach from the tissue level, over the cell level, down to the molecular level. She works in close collaboration with experimental and clinical researchers from the university hospitals Leuven, focusing on the development of mathematical models of impaired healing situations and the in silico design of novel treatment strategies. She is scientific coordinator of Prometheus, the skeletal tissue engineering division of the KU Leuven. Her research is financed by European, regional and university funding (up to date 3.5 M€ as PI and co-PI). In 2011 she was awarded an ERC starting grant to pursue her research.
Title: Study of molecular and cellular properties allowing self-sustenance of growth plates during development
Summary: Growth plates are essential for endochondral ossification of long bones. Attempts to reverse engineer growth plates are of central interest to regenerative therapies that aim to restore large and non-healing bone defects in healthy patients as well as patients suffering from congenital skeletal disorders. In this project we will study the molecular and cellular properties that allow self-sustenance of growth plates during development with the aim of identifying information essential to reverse engineer a growth plate like structure in vitro.
Title: Improved in-process control for the development of skeletal tissue engineering combination products by multimodular 3D imaging
Summary: The strategy of this project is to monitor/image online in a non‑invasive manner each stage in the development of a novel skeletal combination product (SCP) using a combination of two or more non-destructive, 3D imaging modalities (= multimodular imaging) as in-process control suitable for implementation in a commercial/clinical manufacturing environment. This multimodular imaging approach allows to better understand and control the cell behaviour in SCPs and to screen the SCPs for their osteo- and chondrogenic performance, and will be useful in ensuring each stage of development of a novel SCP is well-controlled, consistent, reproducible and well-regulated, leading to an end product that will be safe and effective for clinical applicability and that meets the EMEA regulations. Hence, it allows a higher selectivity, more robustness, more control and a significant decrease in analysis time due to the (partial) replacement of histomorphometry.
Title: Optimization of calcium phosphate-based biomaterials for intra-oral bone regeneration
Summary: Facial traumas, bone resections due to cancer, periodontal diseases and bone atrophy following tooth extractions often lead to alveolar bone defects. Guided Bone Regeneration using synthetic calcium phosphate-based biomaterials has been promoted as a promising approach to restore dental function. The ideal bone substitute in the dental field is expected to serve as an integrated and slowly biodegradable 3D environment which properly satisfies biocompatibility, osteoconductivity and ideally osteoinductivity. It has been shown that the biological performance of these grafts are mutually related to their structural characteristics and can be modulated by physico-chemical properties such as interconnected porosity, mechanical integrity, chemical composition, surface topology and dissolution behavior. Therefore, the general aim of this project is to better understand the influence of micro and Nano-scale topographical characteristics of calcium phosphate-based biomaterials on their bone formation capacity in order to design optimized biomaterials for intra-oral bone regeneration which can be produced by 3D printing methods.
Title: Computational strategies to bring in silico bone tissue engineering models from the bench to the bed side
Summary: Bone tissue engineering (TE), the field that combines knowhow from medical and engineering sciences to come up with solutions for large or non-healing fractures, is struggling to make the transition from the bench to the bedside. Various reasons exist and they come down to the fact that the field is not able to translate the scientific progress into robust and high-quality products tailored to specific patient needs. Computational models are interesting tools to aid in this translation. Currently, a variety of models has been developed for various TE processes such as the biological processes taking place inside the bioreactor used for preparation of the TE products or the bone regeneration model inside the patient itself. This PhD project aims to bring both aforementioned computational models one step closer to the end-user, being the TE product manufacturers and the clinicians. The bioreactor model will be used in an optimization setting that will allow to determine the optimal bioreactor settings for a maximal desired biological response. The fracture healing model will be firstly reduced and subsequently used in an optimization setting to allow the clinician to determine, based on clinical data, the optimal treatment strategies for specific patients (personalized health care) or for a group of patients (in silico clinical trial).
Title: Biomimetic process design for tissue regeneration : modelling the growth plate biology
Summary: Endochondral ossification is a complex process involving a myriad of influencing factors. Signalling pathways precisely navigate mesenchymal stem cells trough the correct cascades. A detailed understanding of these cascades will enable us to develop efficient and robust tissue engineering products. A mathematical model is an interesting tool to study the different pathways involved in endochondral ossification as well as their interactions. In this project we will focus in particular on the BMP and Wnt pathways, their interactions and the way they determine the switch between the proliferation and hypertrophy program in growth plate chondrocytes.
Niki D. Loverdou
Title: Metabolomics as a high-throughput tool for the optimization in stem cell bioprocessing in the context of Bone Tissue Engineering
Summary: The creation of successful cell-based solutions for bone tissue engineering questions depends on the quality of the ground substances as well as the biomanufacturing process bringing these ground substances together. One of these ground substances are the cells and a good control of cell state and fate is important to arrive at robust constructs. High throughput techniques generate massive amounts of data that could be used for control purposes, however, it is not straightforward to derive the proper conclusions from the deluge of data. Computational models can assist in endeavor. Previously, modeling efforts have focused on the simulation of gene regulatory networks to monitor and control the differentiation process of the cells. In this PhD, the metabolic aspects will be studied in depth as growing evidence places metabolic regulation at the heart of many cellular processes. Adding a metabolic component to the existing models should allow for a much more comprehensive study of cell state and fate.
Title: 4D non-destructive characterization of tissue formation during dynamic bioreactor processes using a model-supported contrast enhanced computed tomography approach
Summary: Tissue engineering (TE) is still facing challenges with respect to the quality of its products. Advancing engineering aspects lacking in the field will be crucial in order to tackle these challenges. Bioreactor technology is one of these enabling technologies that helps to obtain high TE product quality as it allows for controlled in vitro formation of 3D neo-tissues (cells + extracellular matrix). As these neotissue are 3D dynamic structures with complex spatial heterogeneity, traditional 2D imaging techniques are insufficient to characterize them, assess their quality or investigate their formation dynamics. This PhD project aims to incorporate a novel (in-house designed) stand-alone automated perfusion bioreactor system within a nanofocus computed tomography (CT) device for 4D imaging (space + time) of neo-tissue formation. To visualize the soft tissues a range of noninvasive contrast agents will be evaluated for their staining potential and binding kinetics to the biological tissues. Novel in silico models, incorporating the dynamic aspects of bioreactor culture, will be developed to better interpret imaging read-outs and optimize the contrast-enhanced CT imaging process.
Title: In silico design of patient-specific treatment strategies for large bone defects
Summary: Bone tissue engineering (TE) is a promising alternative for the treatment of large bone defects. In the current state of the art scaffolds are seeded with cells and subsequently implanted. Despite some successful studies, bone TE to date still suffers from unpredictable and qualitatively inferior results. Moreover, even when satisfactory and reproducible results are obtained in an ectopic implantation site, this does not necessarily mean good results will be obtained in orthotopic implantation sites. An orthotopic environment imposes additional requirements on the construct as it is an environment that is substantially different from the ectopic site in terms of biological and mechanical requirements (signals coming from the host, host-construct interaction and integration, and mechanical stability). In this project, a mathematical model will be developed that will focus on the biological process taking place after implantation of the TE construct in an orthotopic site, in close collaboration with experimental partners. Special attention will be paid to the signals coming from the host on the one hand (e.g. angiogenesis) and signals coming from the construct itself (cells, biomaterials) on the other hand.