A research team from Xi’an Jiaotong University has developed a method for bioprinting skeletal muscle tissue whose cells align in directions that mirror the architecture of real human muscle.

The team’s work addresses a persistent challenge in regenerative medicine: while existing bioprinting techniques can replicate the external shape of muscle tissue, the cells inside printed structures typically remain disorganized. Disorganized cells cannot fuse into functional muscle fibers or contract efficiently, a problem that means printed tissue is mechanically weak.

Using electric forces to direct cell behavior

The team used electrohydrodynamic (EHD) bioprinting, a technique that applies a strong electric field — approximately 3,000 volts — to pull liquid bioink into extremely fine jets. Unlike conventional bioprinting, which extrudes material through a nozzle, EHD printing offers higher resolution but had previously provided little control over internal cell arrangement.

A research team from Xi'an Jiaotong University has developed a method for bioprinting skeletal muscle tissue whose cells align in directions that mirror the architecture of real human muscle.

The researchers reformulated the bioink by combining alginate, a printable gel, with fibrin, a natural protein involved in blood clotting and wound healing. When the electric field stretched the bioink during printing, the fibrin reorganized from scattered clusters into aligned nanofibers pointing in the same direction as the printed filament. Embedded cells then oriented themselves along those fibers.

“You can print the muscle-like shape, but the cells don’t know which way to pull,” said Professor Jiankang He, corresponding author of the study published in the International Journal of Extreme Manufacturing, and Professor of Mechanical Engineering at Xi’an Jiaotong University.

“As the material aligns, the cells follow,” added Ayiguli Kasimu, 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.”

The team also incorporated conductive polymers into the bioink to support electrical signal transmission across the tissue.

“Muscle tissue relies on electrical signals to coordinate contraction, and the conductive additives allowed the printed constructs to transmit these signals,” said Assistant Professor Zijie Meng, co-corresponding author at Xi’an Jiaotong University.

When implanted into animal models with muscle defects, the printed constructs supported new muscle formation and improved functional recovery. 

The researchers noted that the molecular mechanisms governing fibrin’s response to electric fields require further study, and that cell density and material chemistry will need additional optimization.