mERCATOR: Engineering Regenerative CAllus-Tissue ORganoids for compromised long bone defects

Independent living is an important part of healthy aging and is highly dependent on mobility and mental health. Mobility is largely determined by the musculoskeletal system, which deteriorates with age. In addition, the loss of mobility implies secondary morbidities such as obesity, type II diabetes and cardiovascular disease, leading to increased mortality. One of the most common reasons for hospitalization due to skeletal problems is bone fractures. This is why the ability to guide the bone repair process is so important. Our understanding of bone repair at the molecular and cellular level is still incomplete. The aim of this project is to create a tissue engineering solution that will improve the clinical outcome in elderly patients. Hence, we will map the events that take place during bone regeneration at the level of an individual cell, and compare them with biological development processes. Our innovative strategy is based on the comprehensive analysis of regeneration in a clinically relevant non-union model, including the ignition phase. Next, we will establish a mathematical model of these events to define the critical cell populations necessary for successful healing. We will strive to use the knowledge obtained from this model in order to develop cartilaginous organoids, reengineering a 'callus' implant for the healing non-union bone fractures. This project will contribute towards the rational and high-precision engineering of efficient bone regenerating implants .