Deciphering the non-linear mechanical properties of engineered enthesis tissues through the use of tailored composite biohybrids

The field of tissue engineering has clearly identified the crucial role of mechanical properties and forces acting on cells on various biological processes. Bioelectricity also affects several physiological processes such as cell differentiation and motility. Despite the crucial role of these physical cues, the current research in biomechanics treats cells and tissues as linear elastic materials which is in steep contrast with the experimental evidence. Moreover, there is a knowledge gap of how these cues interact and affect cell behaviour. In this project we propose a novel experimental approach that can capture the actual mechanical and electromechanical behavior of cells and tissues with nanoscale resolution. As model systems, periosteum cells and skeletal organoids developed through scaffold-free strategies will be tested. This biological system will be further used to produce tissues that mimic the transition zone that connects bone to tendon, known as enthesis. Enthesis possesses zones with varying mechanical properties and pronounced non-linear mechanical behaviour, thus provides an excellent biological system for the application of the proposed experimental method. Finally, the knowledge that will be generated from the initial phase of the project will be used to understand the onset, progression and possible treatment of diseases related to mechanical damage of these tissues, such as inflammatory arthritis, tendinopathy and enthesopathy.