Hydrogels are among the most promising materials in modern biomedicine. They are soft, water-rich networks that can resemble the physical environment of living tissue, making them useful for drug delivery, wound treatment, tissue engineering and regenerative medicine. Yet one of biology’s most important design principles remains difficult to reproduce in these materials: structural anisotropy, in which microscopic components are aligned in a preferred direction. A new study published in Nature introduces a manufacturing strategy that could make highly organized hydrogel structures considerably easier to produce.
The method, called shear-extensional in situ particle-to-fibre transformation, or SHIFT, converts microscopic particles embedded within a hydrogel into long, aligned fibres during extrusion. Rather than fabricating fibres separately and assembling them afterward, SHIFT creates them inside the flowing material itself. The researchers show that the process can generate hydrogel microfibres approximately 5 to 30 micrometres in diameter, dimensions comparable to important biological structures and small enough to influence how cells organize and mature.
The central idea behind SHIFT is a carefully controlled two-phase transformation. The starting material contains discrete particles distributed throughout a surrounding hydrogel matrix. As this particle-embedded hydrogel passes through an extrusion system, the particles and the matrix undergo opposite phase changes at the same time. Under the combined effects of shear and extensional flow, the particles are stretched, reshaped and drawn into continuous, highly oriented fibre-like structures. The surrounding matrix stabilizes the emerging fibres, preserving their alignment as the material exits the nozzle.
This behaviour differs from conventional hydrogel printing, in which the printed material generally retains the shape and resolution imposed by the nozzle or printing path. In SHIFT, the final internal architecture can be much finer than the apparent dimensions of the printed feature. The process therefore functions as an in situ subvoxel manufacturing method: structures smaller than the nominal printed volume are generated within the flowing ink. That ability could allow researchers to create aligned features without relying exclusively on extremely small nozzles, complex templates or laborious post-processing.
The physics of the transformation is dominated by extensional flow, a type of deformation that stretches material along the direction of movement. Shear forces help orient the particles and matrix near the walls and within the flow field, while extension elongates the dispersed phase into narrow strands. The balance between viscosity, interfacial forces, gelation behaviour and extrusion conditions determines whether the particles remain discrete, deform into elongated domains or transform into stable microfibres. By controlling these parameters, the researchers established a route for turning initially isotropic droplets or particles into anisotropic structures.
The result is a hydrogel with an internal organization that resembles the aligned architecture found throughout the body. Muscle, tendon, nerve and many connective tissues rely on directional arrangements of cells and extracellular matrix to transmit force, guide movement or conduct signals. In ordinary isotropic gels, cells may spread in random orientations because the surrounding material provides few physical cues. SHIFT-generated fibres offer contact guidance, giving cells a directional surface along which they can elongate, migrate and assemble.
The biological consequences were particularly notable in muscle-related experiments. The pronounced anisotropy of the printed hydrogels supported the formation of exceptionally long myotubes in vitro. Myotubes are elongated, multinucleated structures that develop as muscle precursor cells fuse during the early stages of muscle formation. Their length and alignment are important indicators of maturation and function. By providing a continuous directional microenvironment, the SHIFT material helped guide muscle cells into architectures more closely associated with native tissue.
The researchers also report accelerated regeneration in a model of volumetric muscle loss, a severe injury in which a substantial amount of muscle is destroyed and the body cannot fully repair the missing tissue on its own. Such injuries remain challenging because successful reconstruction requires more than filling a defect: new muscle must develop with the correct organization, orientation and mechanical connectivity. The aligned hydrogel architecture produced through SHIFT appears to provide a more instructive scaffold for regeneration than a randomly structured material, although further studies will be needed to establish how the approach performs across different injury types and over longer periods.
A major attraction of SHIFT is its potential compatibility with accessible manufacturing platforms. The method can be adapted to three-dimensional printing, where the fibre-forming ink is deposited layer by layer, and to microfibre spinning, in which continuous material is drawn into long strands. Because the transformation occurs during flow, it may be possible to integrate the technique into existing extrusion systems rather than building entirely new production pipelines. The approach could therefore serve as an upstream materials-processing strategy for creating anisotropic soft matter before or during final shaping.
By transforming particles into fibres inside a flowing hydrogel, SHIFT offers a new way to overcome one of soft-material engineering’s persistent limitations: reproducing the organized, directional structures that make biological tissues function. The work links fluid mechanics, phase transitions, extrusion printing and regenerative medicine in a single manufacturing concept. If the process can be refined for different polymers, cell types and clinical geometries, it could expand the design space for implants and living tissue scaffolds. More broadly, the study demonstrates that microscopic architecture does not always have to be built piece by piece; under the right flow conditions, it can emerge within the material as it is made.
Subject of Research: In situ transformation of hydrogel particles into aligned microfibres for anisotropic 3D printing and muscle regeneration
Article Title: In situ particle-to-fibre transformation of hydrogels for 3D printing
Article References: Zhou, D., Dou, B., Fan, S. et al. In situ particle-to-fibre transformation of hydrogels for 3D printing. Nature (2026). https://doi.org/10.1038/s41586-026-10883-z
Image Credits: AI Generated
DOI: https://doi.org/10.1038/s41586-026-10883-z
Keywords: hydrogels, SHIFT printing, particle-to-fibre transformation, structural anisotropy, extensional flow, 3D bioprinting, microfibres, tissue engineering, muscle regeneration, regenerative medicine
