Data availability
The raw RNA sequencing data are available in the NCBI under accession number PRJNA1475823 . Source data are provided with this paper.
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Acknowledgements
We acknowledge Z. Wang for help with staining, C. Hua for help with materials preparation, B. Li and C. Yang for help with cell culture. D.Z. acknowledges experimental advice from Y. Wu (University of Oxford), W. Huang (Chinese Academy of Sciences) and Y. Yu (Qingdao University). H.S.O. acknowledges the help with microscopy imaging from S. Tsui (Chinese University of Hong Kong). L.O. acknowledges the general discussions with W. Sun (Tsinghua University), F. Lin (Tsinghua University), Z. Xiong (Tsinghua University), J. A. Burdick (University of Colorado Boulder), M. M. Stevens (University of Oxford), M. Zenobi-Wong (ETH Zurich), X. Wang (Tsinghua University), Y. Lin (Beijing University of Chemical Technology) and L. Bian (South China University of Technology).
Funding
This study was primarily supported by the National Key R&D Program of China (no. 2024YFF0509500), the National Natural Science Foundation of China (nos. 52475305, U25D9019 and 52105306), and the Faculty Startup Funding of Tsinghua University (012-533302004), granted to L.O. as principal investigator or co-principal investigator. Other authors acknowledge the National Key R&D Program of China (nos. 2025YFC3408800 (Q.G.) and 2022YFA1103103 (J.N.)) and the National Natural Science Foundation of China (nos. T2222029 (Q.G.) and 32325025 (H.W.)).
Ethics declarations
Competing interests
L.O., D.Z. and B.D. have applied for patents related to this study (PCT/CN2023/133526, CN117532871A and CN117482288A). Other authors declare no conflicting interests.
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Nature thanks Mark Skylar-Scott and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Extended data figures and tables
Extended Data Fig. 1 Effect of channel geometry on SHIFT process and the resulting SHIFTed microfibers.
a-f, SHIFT process within channels featuring fixed inlet (11 mm) and outlet (1.6 mm) dimensions but distinct contraction-section geometries: a-c, linearly tapered channels with different slope values (the values 0.2, 0.4 and 2 correspond to tanβ, where β denotes the slope angle); d, stepped channel with four segments; e, unilateral hyperbolic channel; f, bilateral hyperbolic channel. i) Schematics depicted the discrete phase deformation through the channel with ii) the representative fluorescence images illustrating the discrete phase shape in different regions of interest (ROI). iii) Fast Fourier transform (FFT) images. iv) Their quantitative analysis revealed the orientation of the discrete phase at ROI and v) representative fluorescence images of subvoxel microfibers. g, Diameter distribution of the resultant fiber obtained from corresponding channels. Data are shown as mean ± SD. n = 180 measurements from three experiments. Green fluorescence indicates 10 wt% gelatin. Scale bars: 200 μm.
Source data
Extended Data Fig. 2 Effects of ink composition, printing parameters, and particle size on SHIFT process.
a-b, Effect of discrete–continuous phase ratio. a, Representative microscopic images of printed lattice constructs using different initial volume ratios of discrete phase to continuous phase. b, Rheological characterizations of dual-phase ink formulated at different initial discrete-to-continuous phase volume ratios: i) oscillatory temperature sweeps (5 °C/min, 1% strain, 1.5 Hz) of heating; ii) oscillation amplitude sweeps (0.1%–2000% strain, 1.5 Hz, at 32 °C); and iii) rotational tests (0.01–10 1/s, 10 min, at 32 °C). The dual-phase ink is composed of 10 wt% green-labeled gelatin particles as the discrete phase and 30 wt% poloxamer* as the continuous phase. G’ denotes storage modulus and G” denotes the loss modulus. c-d, Numerical simulation of printing parameters on fiber formation. c, Fitting curves of experimental and simulation results suggest the linear relationship between the droplet deformation and the flow field. d, Simulation results suggest the relationship between the droplet deformation and the extrusion speed. 1-1000× indicated extrusion speeds from 0.1 to 100 mL/min. The ratio of microfiber diameter to particle diameter represents the degree of deformation. e-f, Effect of hydrogel particle size. e, Representative microscopic images of printed constructs in conventional and SHIFT manners show the influence of particle size on subvoxel features. f, Diameter measurements of subvoxel i) particles (n = 60) and ii) microfibers (n = 75). iii) Orientation distribution of microfibers (n = 45). The dual-phase ink is composed of 10 wt% green-labeled gelatin particles as the discrete phase and 30 wt% poloxamer* as the continuous phase. n represents the number of measurements from three experiments. Two-tailed Mann-Whitney U test. Scale bars: 1 mm (a) and 500 μm (e).
Source data
Extended Data Fig. 3 SHIFT 3D printing with a complementary network ink strategy.
a, Representative images of SHIFT-printed lattice constructs on i) day 0 and ii) day 10 using various complementary network hydrogels as the continuous phase. Red fluorescence indicates 10 wt% gelatin as the discrete domain. b, i) Quantitative analysis of the swelling ratio of the printed lattices (Data are shown as mean ± SD. n = 4 structures), ii) the orientation of fibers (n = 40 measurements from four structures), and iii) the diameter of fibers (Data are shown as mean ± SD. n = 60 measurements from four structures). Welch’s ANOVA followed by two-tailed Games-Howell multiple-comparison tests. Before-normalization: as-measured microfiber diameter; after-normalization: diameter corrected to the printed lattice swelling ratio. Alg*, PEGDA* and HAMA* indicate complementary network continuous phase supplemented with poloxamer. c, Representative microscopic images of SHIFT-printed lattice construct using complementary network discrete phase labeled with green (0.5 wt% Alg) and red (10 wt% Gelatin). d, i) Anisotropic centimeter-sized structure fabricated via SHIFT printing in the parallel direction. ii) Representative photographs and microscopic images of multilayered structures fabricated using SilMA/Gelatin as a discrete phase in conventional and SHIFT writing. p > 0.05 was considered as ns (not significant). See source data for the exact p value. Scale bars: 1 mm (a), 500 μm (c).
Source data
Extended Data Fig. 4 Tensile strength and electrical tests on direct ink written filaments.
a, i) Schematics of tensile test and ii) elasticity modulus of traditional bulk filaments (Bulk), particle-embedded filaments (Non-SHIFT), and SHIFT-printed filaments (SHIFT), respectively. Data are shown as mean ± SD. n = 6 structures. Welch’s ANOVA followed by two-tailed Dunnett T3 multiple-comparison tests. b, i) Schematics of tensile test and ii) elasticity modulus of traditional bulk filaments (Bulk), SHIFT-printed filaments based on gelatin particles (SHIFT-Gelatin) and GelMA particles (SHIFT-GelMA), respectively. Data are shown as mean ± SD. n = 6 structures. Welch’s ANOVA followed by two-tailed Dunnett T3 multiple-comparison tests. The continuous phases in panels (a) and (b) are formulated by 30 wt% poloxamer* containing either 5 wt% diacrylated poloxamer (1x) or 10 wt% diacrylated poloxamer (2x). The hydrogel particles were formulated with 7.5 wt% GelMA or 7.5 wt% gelatin. c, Representative microscopic images of the breakpoints after tensile testing and d, Schematic illustration of their crack formation. e, Schematics of electrical test on different types of filaments: poloxamer* i) without a discrete domain, ii) with GelMA particles, and iii) with GelMA microfibers as discrete domains; poloxamer* supplemented with PEDOT:PSS iv) without a discrete domain, v) with plain GelMA microfibers and vi) with GelMA microfibers supplemented with PEDOT:PSS as discrete domains. f, Electrical resistance measurements for the filaments depicted in panel (e). 30 wt% poloxamer*, 10 wt% GelMA, and a total amount of 0.3 wt% PEDOT:PSS were used across different groups. Data are shown as mean ± SD. n = 5 structures. Welch’s ANOVA followed by two-tailed Dunnett T3 multiple-comparison tests. Scale bars: 100 μm (c), 10 mm (e).
Source data
Extended Data Fig. 5 Versatile microfiber generation via SHIFT spinning.
a, Microfibers fabricated through the SHIFT spinning using different nozzles. b, i) Fluorescent intensity comparison of microfibers and ii) Representative images of the fibers before and after heat incubation. The initial microfibers were composed of sacrificial gelatin (label with red fluorescence) and crosslinked 2 wt% HAMA (HAMA*), 1 wt% alginate (Alg*) and 5 wt% PEGDA (PEGDA*), respectively. c, Representative confocal images of live (green) and dead (red) cell (C2C12) staining on day 0 and day 4. Scale bars: 200 μm (a-c).
Source data
Extended Data Fig. 6 Applications of collected SHIFT microfibers.
a, Schematic of cell in-situ delivery strategy with cell-attached fiber. b, i) 3D reconstruction of the matrix material mixed with the sacrificial microfibers. ii) Accumulative release of gelatin from the matrix at different fiber volumes during 37 °C incubation. Data are shown as mean ± SD. n = 5 structures. iii) Representative microscopic images of hydrogel before and after sacrificing microfibers and quantified volume fractions of initial microfibers (red) and eventual fibrous lumens filled with green-label dextran. n = 6 structures. c, i) Representative bright field image (left) and immunofluorescence image (right) of endothelial cells adhering onto gelatin microfibers. ii) Representative bright field images of endothelial cells co-cultured with fibroblasts in bulk and microchannel hydrogels. d, Time-lapse imaging of fiber-embedded iPSC spheroid formation, with cells shown in blue and fibers in orange. e, Fiber-embedded iPSC spheroid generated by co-culturing cells with fibers, cells are shown in blue and fibers in orange. f, i) Representative microscopic images of extracellular fluid (ECF) tracing with Atto-488, showing signal in both the ECF and the microfibers (yellow arrows), and ii) Quantification of the intensity fraction within iPSC spheroids. Data are shown as mean ± SD. n = 3 experiments. Two-tailed Welch’s t-test. g, i) Representative cross-sectional fluorescence image of microfiber-embedded iPSC spheroid on day 4 and ii) Magnified views of the regions of interest (ROIs). Yellow arrows indicate fibers. Scale bars: 150 μm (b), 100 μm (c, e), 200 μm (d, g(i)), 50 μm (f) and 40 μm (g(ii)).
Source data
Extended Data Fig. 7 SHIFT printing of anisotropic constructs for cell alignment.
a, Representative confocal images of live (in green) and dead (in red) cell staining on day 1 and day 4 for different bioink formulations: i) myoblasts embedded in poloxamer as a control, myoblasts embedded in ii) GelMA* and iii) Fibrin* particles experiencing SHIFT printing. b, Normalized proliferation curve of cells under different conditions. GelMA* and Fibrin* indicate complementary network discrete phases supplemented with gelatin. Data are shown as mean ± SD. n = 3 constructs. c, Angular distribution of cell orientation on day 1 (left) and day 4 (right). Zero angle (0°) represents the parallel direction to the printing direction. n = 90 cells. d, Representative microscopic images showing the morphology of myoblast cells and quantified aspect ratios under 2D Culture, Non-SHIFT-Bioprint, and SHIFT-Bioprint conditions. n represents the number of cells. e, The angle of the long axis of the nucleus to the main axis of the images or the parallel axis of the printing direction. Data are shown as mean ± SD. n = 70 cells. f, Myoblast cell-laden “6” structure at centimeter-level fabricated via SHIFT bioprinting. Scale bars: 200 μm (a), 20 μm (d), and 1 mm (f).
Source data
Extended Data Fig. 8 SHIFT anisotropy enhances myotube formation.
a, i) Representative confocal images of live (green) and dead (red) cell staining on day 0 and day 1 and ii) quantification of cell viability over a 7-day culture in Bulk and SHIFTed fiber embedded structures. Data are shown as mean ± SD. n represents the number of constructs. b, i) Representative bright-field images on day 4 and day 7 and ii) normalized proliferation curves of cells in Bulk and SHIFTed fiber embedded structures. Data are shown as mean ± SD. n = 4 constructs. c, Representative fluorescence images showing myotube morphology in 2D and Bulk conditions. d, i) Representative fluorescence images showing Myo+ cells in each group. ii) Distribution of aspect ratios and orientations of Myo+ cells in each group. Zero degree (0°) denotes the axis parallel to the filament direction. n = 80 cells. e, Average myotubes length comparison with existing works. Each point represents a piece of literature ([1] DOI: 10.1016/j.biomaterials.2017.03.026, [2] DOI: 10.1016/j.biomaterials.2018.08.058, [3] DOI: 10.1038/s41467-020-14930-9, [4] DOI: 10.1016/j.carbpol.2021.118444, [5] DOI: 10.1088/1758-5090/ac3aca, [6] DOI: 10.1016/j.actbio.2022.08.037, [7] DOI: 10.1088/1758-5090/acb573, [8] DOI: 10.1002/mabi.202300276). Literature-derived data points were either extracted from original textual descriptions in the cited references or estimated from their quantitative statistical plots. Scale bars: 200 μm (a, b), 1 mm (c) and 100 μm (d(i)).
Source data
Extended Data Fig. 9 SHIFT anisotropy enhances skeletal muscle regeneration.
a, Body weight gain curve over 8-week. Data are shown as mean ± SD. n = 5 mice. b, Gross images of the tibialis anterior (TA) muscle at weeks 2, 4, and 8 for different groups: Sham (Uninjured), VML without implantation (Untreated), bulk hydrogel without cells (Bulk−), SHIFT fiber embedded hydrogel without cells (SHIFT−), bulk hydrogel with cells (Bulk+), and SHIFT fiber embedded hydrogel with cells (SHIFT+). c, Representative H&E (upper) and Masson’s Trichrome (lower) stained images of the VML site at weeks 2 and 4. d, Fibrosis area fraction based on the Masson’s Trichrome staining images at week 8. Data are shown as mean ± SD. n = 5 mice. Welch’s ANOVA followed by two-tailed Dunnett T3 multiple-comparison tests. e, Number of centrally nucleated fibers (CNFs) based on H&E staining images at week 8. Data are shown as mean ± SD. n = 5 mice. Welch’s ANOVA followed by two-tailed Dunnett T3 multiple-comparison tests. Scale bars: 5 mm (b), and 200 μm (c).
Source data
Extended Data Fig. 10 SHIFT anisotropy enhances peripheral nerve regeneration.
a, Schematic of the rat sciatic nerve defect and implanted structures. b, Images of the gastrocnemius muscle on the normal and operated injured sides at week 8 for each group (Bulk, SHIFT, Autograft), and representative transverse sections of Masson’s Trichrome staining from the injured side. c, Quantification of muscle area fraction and collagen area fraction from Masson’s Trichrome images at week 8. Data are shown as mean ± SD. n = 9 measurements from three rats. Welch’s ANOVA followed by two-tailed Dunnett T3 multiple-comparison tests. d, Representative immunostaining of longitudinal section of regenerated nerve tissue (β-III tubulin in red and S100 in green). e, Representative H&E-stained longitudinal sections of regenerated nerve. f, Quantification of β-III tubulin-positive and S100-positive areas. Data are shown as mean ± SD. n = 3 rats. Welch’s t-test with two-tailed. Scale bars: 1 cm (b, upper), 1 mm (b, middle; d, upper; e) and 100 μm (b, bottom; d, middle and bottom).
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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
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DOI: https://doi.org/10.1038/s41586-026-10883-z