Müller Group / Laboratory for Bone BiomechanicsOpen OpportunitiesCombine two exploding fields in computer science: machine learning and agent-based modelling.
Based on preclinical and in vitro studies of cell behaviour and cytokine reaction-diffusion and mechanical tests we have generated an in-house biofidelic agent-based model of the human skeleton and its response to diseases and their treatments. This model reproduces the effects of several widely used osteoporosis treatments on key parameters used to quantify fracture risk. This rule-based approach involves studying bone mechanobiology at the cell scale and extrapolating this to millions of cells at the tissue scale to understand the pharmacokinetics of treatments and identify possible new therapies and approaches to patient-specific treatment.
An alternative approach to in silico prediction of response to treatment is a supervised learning approach where we simply input baseline and follow-up bone scans to a CNN with twelve layers constructed using keras. We then attempt to dive into the black box and quantify what characteristics of the input govern the response of our model. The issue is the clinical data is not big enough to do this well so we use the agent-based model as input to the ML approach to construct a proxy model! This also helps us understand, validate and quantify the uncertainty in the agent-based model. To decide which runs of the agent-based model to use as input to the ML approach to construct the proxy model we use polynomial chaos expansion. - Animal Physiology-Cell, Artificial Intelligence and Signal and Image Processing, Cell Development (incl. Cell Division and Apoptosis), Cellular Interactions (incl. Adhesion, Matrix, Cell Wall), Computation Theory and Mathematics, Modeling and Simulation, Protein Targeting and Signal Transduction
- Bachelor Thesis, Master Thesis, Semester Project
| Rare genetic disorders are defined by a prevalence of fewer than 1/2000 people, are chronic and affect patients throughout their lifespan. Osteogenesis imperfecta (OI) is a heterogeneous group of rare genetic bone disorders. OI is a debilitating condition that involves impaired mobility, high fracture incidence and subsequent limb deformities. No treatment exists today that targets the underlying abnormal collagen structure and organization. The mainstay in pediatric care of OI remains antiresorptive therapy with bisphosphonates, despite concerns of long-term effects on depressed bone turnover. While antiresorptive monoclonal antibody treatments are currently undergoing clinical trials in children and young adults, anabolic treatments that directly increase bone formation are currently approved for adults only and decrease in efficacy over a relatively short time span. The experience with these drugs in OI therapy is limited, as clinical studies are still ongoing.
- Biomedical Engineering, Mechanical and Industrial Engineering
- Bachelor Thesis, ETH Zurich (ETHZ), Internship, Master Thesis, Semester Project
| This project endeavors to explore the dynamic interplay among calcium ions, bone graft substitutes, and resident immune cells in both orthotopic and ectopic environments, employing advanced ratiometric imaging techniques. - Biomaterials, Cellular Interactions (incl. Adhesion, Matrix, Cell Wall)
- Bachelor Thesis, Internship, Master Thesis, Semester Project
| Our goal is to establish a heterocellular 3D printed bone organoid model comprising all major bone cell types (osteoblasts, osteocytes, osteoclasts) to recapitulate bone remodeling units in an in vitro system. The organoids will be produced with the human cells, as they could represent human pathophysiology better than animal models, and eventually could replace them. These in vitro models could be used in the advancement of next-generation personalised treatment strategies. Our tools are different kinds of 3D bioprinting platforms, bio-ink formulations, hydrogels, mol-bioassays, and time-lapsed image processing of micro-CT scans. - Biomaterials, Biomechanical Engineering, Cell Development (incl. Cell Division and Apoptosis), Cellular Interactions (incl. Adhesion, Matrix, Cell Wall), Polymers
- Bachelor Thesis, ETH Zurich (ETHZ), Internship, Master Thesis, Semester Project
| Fracture healing is a complex process that involves inflammation, angiogenesis, and bone remodeling. The remodelling process helps maintain bone density, repair micro-damage that occurs due to everyday activities, and adapt bones to the specific needs of an individual's body. Mechanical loading is a crucial factor in the regulation of fracture healing. The forces and strains experienced by the bone during everyday activities influence the cellular responses, callus formation, bone deposition, remodelling, and, ultimately, the successful recovery of the fractured bone. The mechanisms underlying spatial cell reorganization during loading, which contributes to fracture healing, remain unclear. The project aims to investigate and explore the fracture healing process of mice using spatial transcriptome changes in response to mechanical loading. By shedding light on this aspect, the project aims to contribute to the broader understanding of fracture healing and potentially pave the way for more effective treatment strategies in the future. - Biological Mathematics, Computational Biology and Bioinformatics, Engineering and Technology, Information, Computing and Communication Sciences, Medical and Health Sciences, Physics
- Bachelor Thesis, Course Project, ETH for Development (ETH4D) (ETHZ), ETH Zurich (ETHZ), IDEA League Student Grant (IDL), Internship, Master Thesis, Semester Project
| The project aims at investigating material-induced osteoinduction using the available mouse model of orthotopic or ectopic bone graft substitute application. Through the 3D-3D registration of ex vivo and in vivo multiscale micro-CT images, crucial 3D mineralization of the BGS can be investigated. - Biomedical Engineering, Medical and Health Sciences
- Bachelor Thesis, Semester Project
| Delayed bone healing or failed non-unions account for 5 – 10% of all bone fractures and present a challenging problem in regenerative medicine. The impact of delayed unions or non-unions can be devastating with prolonged rehabilitation, decreased quality of life and significant health care costs. Our lab has conducted fracture healing studies in young and prematurely-aged mouse models with different defect sizes. The aim of this project is to analyse data from mice which exhibit delayed unions and non-unions. - Biomaterials, Biomechanical Engineering
- Bachelor Thesis, Internship, Master Thesis, Semester Project
| Are you a motivated Bachelor's or Master's student willing to learn and develop a micro-Mulitphysics Agent-Based (micro-MPA) model to predict adaptation and regeneration of aged bone? This project offers an opportunity to gain valuable work experience in computational modelling within a highly interdisciplinary Lab. - Biomedical Engineering, Computational Biology and Bioinformatics, Medical and Health Sciences
- Bachelor Thesis, ETH Zurich (ETHZ), Internship, Master Thesis, Semester Project
| Laboratory-grown miniature bones (organoids) can facilitate the investigation of the biology in healthy and diseased human bone, thereby replacing animal experiments and providing a mechanistic understanding of bone remodeling. The goal of this research is to establish an in vitro technique for volumetric 3D bioprinting of structurally complex human bone organoids. This bone organoid has the potential to enable studying human bone remodeling in the laboratory without the need for animal models. - Biomaterials, Biotechnology
- Internship, Master Thesis, Semester Project
| 3D in vitro models provide a valuable way to study human biology without using animals. However, these models are primarily based on poorly defined animal-derived hydrogels, such as Matrigel or collagen. This limits our detailed understanding of cell-material interactions in bone development, maintenance, and repair. Importantly, these mechanisms are often disrupted in various bone diseases, highlighting the needs for more advanced in vitro models. - Biochemistry and Cell Biology, Chemistry, Engineering and Technology, Medical and Health Sciences
- Semester Project
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