Neuromuscular junction (NMJ) disorders are caused by miscommunication between neurons and muscles in the body and severely impact quality of life. Current efforts to develop treatments are challenged by the biological complexity of these systems and rely heavily on extensive animal experimentation. In this project, we aim to develop electroactive hydrogel systems to support 3D motor neural networks derived from human induced pluripotent stem cells (hiPSCs). Hydrogels, which mimic the soft properties of brain tissue, provide a promising platform for tissue regeneration. By integrating conducting polymers—soft materials compatible with extracellular matrix (ECM) components—the proposed electroactive gels will create unique biochemical and biophysical environments that support the growth of functional motor neural networks from hiPSCs. Additionally, the electrical properties of these gels will allow for real-time, non-invasive monitoring of cell development. We will incorporate the gel-based neural networks into the MUSBit™ device developed by Biond Solutions BV, which currently supports 3D skeletal muscle organoids. By connecting the motor neural networks to skeletal muscle tissue, we will create a highly biomimetic in vitro NMJ model system, offering an invaluable tool for biologists and clinicians to study NMJ disorders and advance regenerative medicine.
