ENGINEERING AN IN VITRO MODEL OF HUMAN MUSCLE DYSTROPHY FOR HIGHTHROUGHPUT SCREENINGS AND DEVELOPMENT OF THERAPEUTIC STRATEGIES

In this research project, we are aimed at producing in vitro human skeletal muscle myotubes which exhibits functional properties by a proper design of the in vitro artificial niche. An in vitro model of human dystrophic skeletal muscle would be suitable for therapy screenings, drug developments and for the investigation of relevant biological mechanisms in a highthroughput fashion. The process of development of new therapeutic strategies is characterized by high costs incurred over a period of several years before any returns from the developmental efforts of the researchers are realized. In this context, it would be of paramount importance to develop a human derived tissue-based assay and technologies able to provide robust and reproducible biological and physiological functional response representative of human skeletal muscle and muscle dystrophy. We will couple and integrate in an efficient manner different skills and competences from the biology, biotechnology and chemical engineering worlds to mimic in vitro the dominant physiological stimuli that guide human dystrophic myotubes formation. This integration will offer the unique capability of: i) culturing dystrophic myoblasts on a hydrogel with mechanical properties resembling those of muscular tissue in vivo; ii) performing microcontact printing of proteins on the hydrogel surface in order to spatially organize myoblasts and direct their alignment; iii) coupling physiological electrical stimulation to the cell cultures in order to study the functional activity. The outcomes of our project have the general perspective of guiding the design of tissue engineering systems as well as to utilize engineered tissues as controllable biological human models for studies of development, remodeling, physiological and biological responses of diseases. These outcomes could be an innovative technological resource for other research centers involved in the study of genetic diseases.