Researchers at Chongqing Medical University in China and the Chinese University of Hong Kong have published a comprehensive review on the use of 3D printing in skeletal muscle-on-a-chip (SMoC) systems. The paper, appearing in ScienceDirect, highlights how printing methods are being applied to fabricate microfluidic devices, arrange muscle fibers, and create biomimetic scaffolds for studying skeletal muscle physiology and related diseases.
Organ-on-a-chip platforms integrate microfluidics, bioengineering, and cell biology to reproduce key functions of human tissues. While models exist for the lung, heart, liver, kidney, and brain, replicating skeletal muscle has remained a challenge due to its layered fiber architecture, high metabolic demand, and dependence on neuromuscular signaling.
Additive manufacturing has been adopted in several aspects of SMoC construction. Industrial-grade printing methods such as fused deposition modeling (FDM) and stereolithography (SLA) have been used to build chip holders or molds. SLA, which cures liquid resin with ultraviolet light, has provided high precision in fabricating microchannel structures. Bioprinting approaches have extended this further by using live cells and hydrogels as bioinks to form contractile fibers and complex tissue environments.
The review emphasizes that these methods allow precise deposition of materials and cells, enabling layered structures that resemble natural skeletal muscle. For instance, researchers have combined bioprinting with electrospinning to align fibers and improve myotube maturation, or incorporated conductive nanomaterials to enhance cell alignment and electrical responsiveness.
Several studies have demonstrated how SMoCs fabricated with 3D printing can reproduce disease conditions and evaluate therapies. Patient-derived myoblasts from individuals with Duchenne muscular dystrophy have been seeded on chip platforms to assess potential regenerative treatments. Other work has used neuromuscular junction models, combining motor neurons and skeletal muscle fibers, to study myasthenia gravis and amyotrophic lateral sclerosis.
In one approach, photopolymerization-based printing was used to construct chips with polyacrylamide columns acting as anchor points for aligned muscle bundles. These systems enabled quantification of passive tension and contractile force, while also allowing functional assessment under injury conditions. Another study employed SLA-designed molds followed by polydimethylsiloxane (PDMS) casting to build chip bodies for experiments on advanced glycation end-products, which were shown to impair muscle contraction and structure.
SMoC platforms have also been used in environmental studies. A microphysiological system fabricated with 3D printed components allowed researchers to expose chips to normoxic and hypoxic conditions simultaneously, providing a means to analyze oxygen-dependent signaling. More recently, printed muscle chips were sent to the International Space Station National Laboratory, where they were used to examine microgravity effects and screen compounds such as IGF-1 and 15-PDGH inhibitors.
Despite these advances, several obstacles remain. Current printing technologies produce structures at millimeter resolution, which is insufficient for replicating cell-level alignment. Bioinks such as hydrogels often lack the mechanical strength for long-term experiments, and their biocompatibility can limit reproducibility. Evaluating muscle contraction also requires integrated sensors, such as electrodes or strain gauges, which must be incorporated into the chip without disrupting the culture environment.
Material development is another constraint. While biocompatible polymers like PDMS and hydrogels are commonly used, skeletal muscle requires scaffolds with both elasticity and strength to withstand contraction cycles. Researchers have experimented with thermoresponsive polymers, extracellular matrix-derived scaffolds, and hybrid strategies combining 3D printing with electrospinning to enhance structural and functional fidelity.
Future work highlighted in the review includes increasing resolution through multi-nozzle printers, developing new bioinks with improved mechanical and biological properties, and refining culture systems to better mimic muscle metabolism and electrophysiology. 4D printing, where printed structures can change shape or function over time in response to stimuli, has already been applied in preliminary muscle studies. In one example, GelMA fibers seeded with myoblasts were induced to coil into tubular structures, resembling natural muscle bundles and promoting differentiation.
Advances in chip integration are also extending SMoC research into multi-organ systems. Dual and modular chips have been developed to connect skeletal muscle with other tissues, such as bone or liver, via vascular flow. These platforms enable study of systemic interactions, including off-target drug effects and metabolic regulation.
Skeletal muscle-on-a-chip research is still in its early stages, but 3D printing is already central to its progress. By enabling precise chip fabrication, cell arrangement, and scaffold customization, additive manufacturing has made it possible to replicate key structural and functional features of muscle tissue in vitro. According to the review, continued improvements in resolution, materials, and system integration will be necessary for these platforms to fully support disease modeling, drug testing, and studies of muscle physiology.