Publications

Research into the development of therapeutic strategies is basedmainly on animal models and cell cultures. The ability to extrapolatedata from them is limited, and research on new drugs cannot beperformed efficiently. This is especially dramatic in rare diseases,which are intrinsically very heterogeneous. The generation of ad-vanced models using tissue engineering and patient-derived cellsallows fabricating new platforms for studying pathological processesand discovering new potential drugs. Here, we developed a patient-derived 3D functional skeletal muscle for Duchenne muscular dys-trophy (DMD). DMD is the most prevalent neuromuscular diseasediagnosed during childhood. The disease is characterized by pro-gressive degeneration of skeletal and cardiac muscle caused by thelack of dystrophin protein. Although there are several molecules indrug development for DMD, there is no treatment available for pa-tients to date. By using a 3D-printed casting mold, we encapsulatedpatient-derived myogenic precursor cells in a fibrin-composite ma-trix. This platform incorporated two flexible T-shaped pillars thatprovided continuous tension to the tissue, thus allowing the orien-tation of the muscle fibers. Our 3D muscle model expressed maturemuscle markers and responded to electric pulse stimulation (EPS).Besides, contraction dynamics between DMD and control tissueswere shown to be different. Moreover, an increase of damagemarkers after EPS was observed in DMD but not in healthy tissues.Finally, the tissues will be integrated into a microfluidic device tomonitor drug administration. Eventually, the microfluidic systemwill be connected to a biosensors system for the real-time detectionof biomarkers.

JTD Keywords: Casting, Contraction dynamics, Muscular dystrophy