Dreher, S. | bioRxiv Science

bioRxiv2026

Functional primary human 3D skeletal muscle organoids enable exercise and metabolic research

Human skeletal muscle is the principal site of insulin-stimulated glucose disposal and a major mediator of exercise-induced metabolic benefits, yet human models that preserve metabolic and exercise responsiveness remain limited. We generated primary human skeletal muscle organoids from donor-derived CD56+ myoblasts using a collagen-based extracellular matrix and serum-free IGF1-guided differentiation. The organoids formed aligned contractile tissues containing oxidative and glycolytic fiber type-like myotubes, displayed enhanced mitochondrial respiration, insulin-stimulated glucose uptake, and reproducible force generation. Electrical pulse stimulation induced AMPK activation, increased glucose utilization and lactate production, and upregulated canonical exercise-responsive genes including NR4A3 and PPARGC1A. Notably, transcriptional responses to in vitro exercise overlapped with acute exercise responses observed in skeletal muscle biopsies from the same donors. The organoids further detected functional impairments of skeletal muscle performance induced by TGF-{beta}1 and metformin and increased speed generation by testosterone treatment. These findings establish a donor-specific human skeletal muscle platform that recapitulates key features of insulin action and exercise adaptation and may enable mechanistic studies of skeletal muscle metabolism, exercise responsiveness, and therapeutic interventions relevant to diabetes.

Molecular Biology↗

bioRxiv2023

SonoPrint: Acoustically Assisted Volumetric 3D Printing for Composites

Advancements in additive manufacturing in composites have transformed various fields in aerospace, medical devices, tissue engineering, and electronics, enabling fine-tuning material properties by reinforcing internal particles and adjusting their type, orientation, and volume fraction. This capability opens new possibilities for tailoring materials to specific applications and optimizing the performance of 3D-printed objects. Existing reinforcement strategies are restricted to pattern types, alignment areas, and particle characteristics. Alternatively, acoustics provide versatility by controlling particles independent of their size, geometry, and charge and can create intricate pattern formations. Despite the potential of acoustics in most 3D printing, limitation arises from the scattering of the acoustic field between the polymerized hard layers and the unpolymerized resin, leading to undesirable patterning formation. However, this challenge can be addressed by adopting a novel approach that involves simultaneous reinforcement and printing the entire structure. Here, we present SonoPrint, an acoustically-assisted volumetric 3D printer that produces mechanically tunable composite geometries by patterning reinforcement microparticles within the fabricated structure. SonoPrint creates a standing wave field that produces a targeted particle motif in the photosensitive resin while simultaneously printing the object in just a few minutes. We have also demonstrated various patterning configurations such as lines, radial lines, circles, rhombuses, quadrilaterals, and hexagons using microscopic particles such as glass, metal, and polystyrene particles. Furthermore, we fabricated diverse composites using different resins, achieving 87 microns feature size. We have shown that the printed structure with patterned microparticles increased their tensile and compression strength by [~]38% and [~]75%, respectively.

bioengineering↗