ReModel-OP · Identifying strategies to reduce osteoporosis-driven bone loss through the development of microphysiological bone remodeling-on-chip tools

Osteoporosis is a common skeletal disorder characterized by imbalanced bone remodeling, where osteoclast activity is exacerbated leading to increased bone degradation and fracture risk. The socio-economic burden of this disease is elevated in the EU and is expected to further increase in coming years, highlighting the need of improved disease models and drug screening platforms in pre-clinical research. Organ-on-chip (OoC) technology has been demonstrating high potential to replace anima testing in drug screening and pathophysiological modeling, but current output measurements in OoC applications are still mostly limited to end-point assays or require large volume of sample. In addition, bone OoC models competent for exacerbated bone resorption, the main consequence of osteoporosis, are still lacking, indicating a need for improved and more representative models.To address this issue, in this project I aim to identify and validate potential strategies to reduce osteoporosis-driven bone loss, through the establishment of a bone-on-chip model with integrated sensors for online detection of bone degradation biomarkers. I will combine knowledge from disciplines ranging from microfabrication, tissue engineering, molecular biology, imaging and electrochemistry to fabricate osteoclast resorption biomarker sensors and integrate them in OoC models that faithfully replicate the bone microenvironment. My experience in osteoclast biology will be integrated with the extensive expertise of the Brigham and Women´s Hospital - Harvard Medical School in tissue engineering, microfabrication and materials science for the successful implementation of this proposal. These experiences will provide the optimal training environment not only to become a leader in organ-on-chip disease modelling but also to position myself advantageously to succeed in non-academic sectors.