Mathematical models for optimizing experimental design and scale up of bone organoids

Bone is a highly responsive organ that is a structural and mechanical supportive component of our body, and it regulates mineral homeostasis, blood cell generation, body metabolism, and brain functions. Bone undergoes constant remodeling throughout life. It involves the removal of mineralized bone by osteoclasts followed by the formation of the bone matrix through the osteoblasts. That subsequently repairs microdamage, adapts to mechanical and physiological changes, and balances bone resorption and formation. Bone and joint diseases, osteoarthritis, osteoporosis, gout, rheumatoid arthritis, bone marrow disease, and bone-related cancers are financially expensive because of long-term curing periods. At the same time, It required more insight into the biomechanisms that would allow developing the therapeutics or clinical targets for these bone-related diseases. Currently, preclinical bone research mainly depends on the 2D cell culture of mammalian cells and animal experiments, causing substantial financial costs when exposed to drugs or other molecules. 3D systems have become a promising alternative to 2D cell culture to overcome the gap and recapitulate the physiological environment. The bone organoids are 3D self-organized bone tissues with biomimetic features that are created based on bioactive material and differentiated from stem bone stem cells. This project aims to create bone organoids derived from a pediatric patient's human osteoblast cells using dynamic compression bioreactors. Further, we measure several critical properties of these organoids to maintain them for longer and determine their precision and accuracy. These bone organoids are created using compression bioreactors, which require a long time to scale up the production. Therefore we want to develop novel modeling approaches to enhance the efficiency of compression bioreactors process understanding, development, and optimization, allowing scale up the bone organoid. **Your profile:** Candidates with particular interest and prior experience developing mathematical modelling and parameter estimation, programming skills like Python and Matlab are beneficial.

Bone is a highly responsive organ that is a structural and mechanical supportive component of our body, and it regulates mineral homeostasis, blood cell generation, body metabolism, and brain functions. Bone undergoes constant remodeling throughout life. It involves the removal of mineralized bone by osteoclasts followed by the formation of the bone matrix through the osteoblasts. That subsequently repairs microdamage, adapts to mechanical and physiological changes, and balances bone resorption and formation. Bone and joint diseases, osteoarthritis, osteoporosis, gout, rheumatoid arthritis, bone marrow disease, and bone-related cancers are financially expensive because of long-term curing periods. At the same time, It required more insight into the biomechanisms that would allow developing the therapeutics or clinical targets for these bone-related diseases. Currently, preclinical bone research mainly depends on the 2D cell culture of mammalian cells and animal experiments, causing substantial financial costs when exposed to drugs or other molecules. 3D systems have become a promising alternative to 2D cell culture to overcome the gap and recapitulate the physiological environment. The bone organoids are 3D self-organized bone tissues with biomimetic features that are created based on bioactive material and differentiated from stem bone stem cells. This project aims to create bone organoids derived from a pediatric patient's human osteoblast cells using dynamic compression bioreactors. Further, we measure several critical properties of these organoids to maintain them for longer and determine their precision and accuracy. These bone organoids are created using compression bioreactors, which require a long time to scale up the production. Therefore we want to develop novel modeling approaches to enhance the efficiency of compression bioreactors process understanding, development, and optimization, allowing scale up the bone organoid.

**Your profile:**

Candidates with particular interest and prior experience developing mathematical modelling and parameter estimation, programming skills like Python and Matlab are beneficial.

We aim to develop a mathematical model to enhance efficiency in the production of the bone organoid allowing advanced control strategies in experimental design. We use nonlinear differential-algebra equations systems to characterize the model and estimate the critical parameter based on our experimental measurements. Further, the model simulates various input signals to verify and validate the controller performance of bone organoid scale up.

We aim to develop a mathematical model to enhance efficiency in the production of the bone organoid allowing advanced control strategies in experimental design. We use nonlinear differential-algebra equations systems to characterize the model and estimate the critical parameter based on our experimental measurements. Further, the model simulates various input signals to verify and validate the controller performance of bone organoid scale up.

Please get in touch with me to get more detailed information about the project by email or reach out in person at Gloriastrasse 37/39, 8092 Zürich, Switzerland. **Email**: amit.singh@hest.ethz.ch **LinkedIn**: https://www.linkedin.com/in/amit-singh-63373417

Please get in touch with me to get more detailed information about the project by email or reach out in person at Gloriastrasse 37/39, 8092 Zürich, Switzerland.

**Email**: amit.singh@hest.ethz.ch

**LinkedIn**: https://www.linkedin.com/in/amit-singh-63373417