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Project

Precision biomanufacturing of hierarchical joint implants

Osteoarthritis (OA) is a highly prevalent disease, affecting 1 in 8 adults worldwide and is projected to increase by 60% in the next two decades. It is ranked as the 11th highest contributor to global disability, with impact on mobility, physical function, sleep and mood. Large population studies reveal (osteo)chondral injuries as a major risk factor in the development of knee OA. Therapy of OA is limited to removing or modifying existing cartilage autografts and is predominantly palliative and does not regenerate the osteochondral defects. Regenerative Medicine and Tissue Engineering (TE) holds great promise to repair efficiently damaged tissues. A recent paradigm shift in the TE-field underscored the benefit of microtissues/organoids as living-building-blocks to repair larger defects as opposed to single cells. Spheroid and organoid technologies enable cells to follow developmental events in vitro and accomplish their developmental-like programs upon implantation and this “Developmental Engineering” approach is rapidly gaining ground. A possible approach is to use different types of micro-cartilage intermediates (μCI), each type corresponding to the biological properties of the respective zone in the joint. The formation of microtissue based implants is becoming the next frontier in the field of tissue engineering. Despite progress in engineering distinct microtissue modules, their integration in a single complex and potent implant is yet an elusive process. In the BIOARCHiTECT project we propose to address the outstanding issues by developing an end-to-end scalable and highprecision bioprocess, adopting bioreactor and bioprinting technologies starting from single stem cell production through (in silico) design of zonated osteochondral implants. In the PhD position offered, the aim is that you optimize the needed in vitro cell expansion processes by making use of novel high-throughput bioreactors and scaling it up to clinically relevant cell numbers. You will develop online sensor read-outs to monitor the growth kinetics of the cell populations while adapting the feed-rate based on the information gathered. You will combine hardware sensors with data-driven soft sensing approaches and apply model-based control methods to steer the feed-rate, temperature and dissolved oxygen. To develop the models of the considered non-linear time-varying cellular systems, you will apply and combine methods from time series modelling and machine learning, including deep learning.

Date:15 Feb 2023 →  Today
Keywords:cell expansion, cell-based therapies, bio-process, model predictive control, novel high-throughput bioreactors
Disciplines:Tissue engineering, Human health engineering
Project type:PhD project