Bioprinting muscle that knows how to align its cells just as in the human body

(Press-News.org) Building functional human muscle in the laboratory has long been a goal of regenerative medicine, but one stubborn obstacle remains: real muscle is not just a mass of cells. Its strength and function depend on exquisitely ordered myofibers, all aligned in precise directions that vary from one muscle to another. Reproducing that internal order has proved far harder than shaping muscle tissue into the right external form.

Published in the International Journal of Extreme Manufacturing, a research team from Xi'an Jiaotong University has now found a way to solve both problems at once. By using electric forces during the electrohydrodynamic bioprinting process, they have created living muscle tissues whose cells naturally line up just as they do in the human body, showing how electric forces can be used not just to precisely bioprint tissue, but to quietly instruct cells how to organize themselves.

Skeletal muscles come in many forms. Some fibers run in long, parallel bundles that power our arms and legs. Others curve or fan out, helping us grip, chew or control movement with precision. Despite these differences, all muscles share a common microscopic feature: their cells are highly aligned. This alignment allows individual muscle cells to fuse into long fibers and contract efficiently. Without it, muscle tissue is weak and poorly functional.

Existing tissue-engineering methods can encourage cells to align, but usually only in flat sheets or simple structures. Bioprinting, by contrast, excels at building three-dimensional shapes, yet the cells inside printed tissues often remain disorganized. "You can print the muscle-like shape, but the cells don't know which way to pull," explains Prof. Jiankang He, corresponding author of the study and a professor of mechanical engineering at Xi'an Jiaotong University.

The team turned to a technique called electrohydrodynamic, or EHD, bioprinting. Unlike conventional bioprinting extruding soft materials through a nozzle, EHD bioprinting uses a strong electric field to pull out extremely fine jets of liquid. This allows much higher printing resolution, but until now it offered little control over how cells behave inside the printed material.

Their breakthrough came from redesigning the bioink itself. Researchers combined alginate, a printable gel commonly used in bioprinting, with fibrin, a natural protein that helps blood clot and plays a key role in wound healing. Fibrin is also electrically sensitive, so when the bioink is stretched by the electric field during printing, these tiny and randomly scattered fibrin clusters are pulled apart and reorganized into long and evenly aligned nanofibers.

This transformation occurs at a critical moment known as the Taylor cone stage, when the liquid jet first forms under high voltage. At around 3,000 volts, the fibrin rearranges itself into nanoscale fibers that all point in the same direction as the printed filament. To the cells embedded in the gel, these fibers act like microscopic tracks. The cells sense the aligned structure around them and orient themselves accordingly.

"As the material aligns, the cells follow," says Ayiguli Kasimu, a doctoral researcher and first author of the study. "The electric field is effectively building a road system at the nanoscale, and the cells naturally grow along it."

Because the alignment emerges during printing, the method offers unusual freedom. By simply changing the path of the printer nozzle, the researchers produced muscle tissues with straight fibers, curved fibers, or circular arrangements, all with tightly aligned cells inside. This makes it possible to mimic the diverse architectures seen in real muscles, rather than forcing every tissue into the same simple pattern.

To make the printed tissues even more muscle-like, the team added conductive polymers to the bioink. "Muscle tissue relies on electrical signals to coordinate contraction, and the conductive additives allowed the printed constructs to transmit these signals," explains Assistant Prof. Zijie Meng, co-corresponding author of the study at Xi'an Jiaotong University. The result was not only better electrical properties, but also healthier muscle development. Cells fused more efficiently into mature muscle fibers and showed stronger expression of muscle-specific proteins.

The real test came in living organisms. When implanted into animal models with muscle defects, the printed tissues supported new muscle formation and significantly improved functional recovery. The aligned and conductive constructs did not just survive in the body; they actively helped restore lost muscle function.

Beyond its immediate implications for muscle repair, the study highlights a broader idea: the electric field can be used as a powerful tool to shape living matter from the inside out. The researchers show that the alignment arises from a combination of electrical and mechanical effects. Differences in electrical charge cause fibrin to migrate and reorganize, while the intense stretching of the material during printing elongates fibrin clusters into fibers. Together, these processes create a finely ordered environment that cells instinctively understand.

The authors acknowledge that more work lies ahead. The molecular details of how fibrin responds to electric fields are not yet fully understood, and further studies will be needed to optimize cell density, material chemistry and long-term performance. Still, the concept is clear and compelling.

By turning electric field force into a biological design signal, the Xi'an Jiaotong team has shown a new way to bioprint living tissues that look and behave more like the real thing. If extended to other organs, this approach could help bridge the long-standing gap between printed shapes and true biological function, bringing regenerative medicine one step closer to rebuilding the body.

International Journal of Extreme Manufacturing (IJEM, IF: 21.3) is dedicated to publishing the best advanced manufacturing research with extreme dimensions to address both the fundamental scientific challenges and significant engineering needs.

Maintained #1 in Engineering, Manufacturing for consecutive years Average time to First Decision after Peer Review: 34 days Open Access Publishing with APC Waivers Visit our webpage, like us on Facebook, and follow us on Twitter and LinkedIn.

END