Bioengineering an Innervated 3D Skeletal Muscle Model to Replicate Contractile Dysfunction in Neuromuscular Disorders

2026-07-22

Neuromuscular disorders (NMDs) encompass a diverse group of diseases that severely impact patients' quality of life and reduce life expectancy. Despite the urgent need, only a handful of these disorders are currently treatable. A major barrier to therapeutic development is the lack of humanized models that can accurately reflect the complex neuromuscular phenotypes observed in patients. Recent advancements in cell culture techniques have enabled the development of functional 3D-tissue-engineered skeletal muscles (3D-TESMs), offering a promising platform to study NMDs. However, the integration of motor neurons and neuromuscular junctions (NMJs) in these models remains challenging. In this project, I aim to bridge this critical gap by leveraging my background in developing in vitro muscle models and the host lab's expertise in peripheral nerve biology. Together, we will develop innervated cell models capable of contractile functioning using human-induced pluripotent stem cell-derived muscle cells and motor neurons. By integrating 3D-printing technologies and a customized high-density multielectrode array, I plan to generate two innervated 3D-TESM cell models to study both the muscular and neuronal aspects of NMDs. As a proof-of-concept, these models will be applied to study the effects of axonal Charcot-Marie-Tooth disease (CMT2), illustrating their potential for investigating NMDs. Overall, the development of innervated 3D-TESMs will represent a significant step forward in creating more accurate humanized systems to study NMDs and accelerate the development of effective therapeutics.

Belgium

2026-01-01