Our publications are classified into four areas: (1) Polymers and Soft Matter, (2) Advanced (Bio)Manufacturing, (3) Biomaterials, and (4) Bioengineering. Some of them are theoretical works or experimental works including theoretical component. Please click tags to sort papers of each category and Google Scholar for citations.
2025
6.
Daniel A. Rau, Myoeum Kim, Baoxing Xu, Li-Heng Cai
Modular soft stretchable low-cost elastomers for stereolithography printing structures with extreme dissipative properties Working paper
Submitted, 2025.
Links | Tags: Advanced (Bio)Manufacturing, Polymers and Soft Matter
@workingpaper{Gong,
title = {Modular soft stretchable low-cost elastomers for stereolithography printing structures with extreme dissipative properties},
author = {Daniel A. Rau and Myoeum Kim and Baoxing Xu and Li-Heng Cai},
url = {10.26434/chemrxiv-2024-pj7s0},
doi = {10.26434/chemrxiv-2024-pj7s0},
year = {2025},
date = {2025-11-01},
urldate = {2025-11-01},
howpublished = {Submitted},
keywords = {Advanced (Bio)Manufacturing, Polymers and Soft Matter},
pubstate = {published},
tppubtype = {workingpaper}
}
2024
5.
Myoeum Kim, Shifeng Nian, Daniel A. Rau, Baiqiang Huang, Jinchang Zhu, Guillaume Freychet, Mikhail Zhernenkov, Li-Heng Cai
3D printable modular soft elastomers from physically cross-linked homogeneous associative polymers Journal Article
In: ACS Polymers Au, vol. 4, no. 2, pp. 98–108, 2024.
Abstract | Links | Tags: Advanced (Bio)Manufacturing, Polymers and Soft Matter
@article{Kim2024,
title = {3D printable modular soft elastomers from physically cross-linked homogeneous associative polymers},
author = {Myoeum Kim and Shifeng Nian and Daniel A. Rau and Baiqiang Huang and Jinchang Zhu and Guillaume Freychet and Mikhail Zhernenkov and Li-Heng Cai},
doi = {10.1021/acspolymersau.3c00021},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {ACS Polymers Au},
volume = {4},
number = {2},
pages = {98–108},
abstract = {Three-dimensional (3D) printing of elastomers enables the fabrication of many technologically important structures and devices. However, there remains a critical need for the development of reprocessable, solvent-free, soft elastomers that can be printed without the need for post-treatment. Herein, we report modular soft elastomers suitable for direct ink writing (DIW) printing by physically cross-linking associative polymers with a high fraction of reversible bonds. We designed and synthesized linear-associative-linear (LAL) triblock copolymers; the middle block is an associative polymer carrying amide groups that form double hydrogen bonding, and the end blocks aggregate to hard glassy domains that effectively act as physical cross-links. The amide groups do not aggregate to nanoscale clusters and only slow down polymer dynamics without changing the shape of the linear viscoelastic spectra; this enables molecular control over energy dissipation by varying the fraction of the associative groups. Increasing the volume fraction of the end linear blocks increases the network stiffness by more than 100 times without significantly compromising the extensibility. We created elastomers with Young's moduli ranging from 8 kPa to 8 MPa while maintaining the tensile breaking strain around 150%. Using a high-temperature DIW printing platform, we transformed our elastomers to complex, highly deformable 3D structures without involving any solvent or post-print processing. Our elastomers represent the softest melt reprocessable materials for DIW printing. The developed LAL polymers synergize emerging homogeneous associative polymers with a high fraction of reversible bonds and classical block copolymer self-assembly to form a dual-cross-linked network, providing a versatile platform for the modular design and development of soft melt reprocessable elastomeric materials for practical applications.},
keywords = {Advanced (Bio)Manufacturing, Polymers and Soft Matter},
pubstate = {published},
tppubtype = {article}
}
Three-dimensional (3D) printing of elastomers enables the fabrication of many technologically important structures and devices. However, there remains a critical need for the development of reprocessable, solvent-free, soft elastomers that can be printed without the need for post-treatment. Herein, we report modular soft elastomers suitable for direct ink writing (DIW) printing by physically cross-linking associative polymers with a high fraction of reversible bonds. We designed and synthesized linear-associative-linear (LAL) triblock copolymers; the middle block is an associative polymer carrying amide groups that form double hydrogen bonding, and the end blocks aggregate to hard glassy domains that effectively act as physical cross-links. The amide groups do not aggregate to nanoscale clusters and only slow down polymer dynamics without changing the shape of the linear viscoelastic spectra; this enables molecular control over energy dissipation by varying the fraction of the associative groups. Increasing the volume fraction of the end linear blocks increases the network stiffness by more than 100 times without significantly compromising the extensibility. We created elastomers with Young's moduli ranging from 8 kPa to 8 MPa while maintaining the tensile breaking strain around 150%. Using a high-temperature DIW printing platform, we transformed our elastomers to complex, highly deformable 3D structures without involving any solvent or post-print processing. Our elastomers represent the softest melt reprocessable materials for DIW printing. The developed LAL polymers synergize emerging homogeneous associative polymers with a high fraction of reversible bonds and classical block copolymer self-assembly to form a dual-cross-linked network, providing a versatile platform for the modular design and development of soft melt reprocessable elastomeric materials for practical applications.
4.
Jinchang Zhu, Yi He, Yong Wang, Li-Heng Cai
Voxelated bioprinting of modular double-network bio-ink droplets Journal Article
In: Nature Communications, vol. 15, pp. 5902, 2024.
Abstract | Links | Tags: Advanced (Bio)Manufacturing, Biomaterials, Theory
@article{Zhu2024,
title = {Voxelated bioprinting of modular double-network bio-ink droplets},
author = {Jinchang Zhu and Yi He and Yong Wang and Li-Heng Cai},
url = {https://doi.org/10.1038/s41467-024-49705-z},
doi = {10.1038/s41467-024-49705-z},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Nature Communications},
volume = {15},
pages = {5902},
abstract = {Analogous of pixels to two-dimensional pictures, voxels—in the form of either small cubes or spheres—are the basic building blocks of three-dimensional objects. However, precise manipulation of viscoelastic bio-ink voxels in three-dimensional space represents a grand challenge in both soft matter science and biomanufacturing. Here, we present a voxelated bioprinting technology that enables the digital assembly of interpenetrating double-network hydrogel droplets made of polyacrylamide/alginate-based or hyaluronic acid/alginate-based polymers. The hydrogels are crosslinked via additive-free and biofriendly click reaction between a pair of stoichiometrically matched polymers carrying norbornene and tetrazine groups, respectively. We develop theoretical frameworks to describe the crosslinking kinetics and stiffness of the hydrogels, and construct a diagram-of-state to delineate their mechanical properties. Multi-channel print nozzles are developed to allow on-demand mixing of highly viscoelastic bio-inks without significantly impairing cell viability. Further, we showcase the distinctive capability of voxelated bioprinting by creating highly complex three-dimensional structures such as a hollow sphere composed of interconnected yet distinguishable hydrogel particles. Finally, we validate the cytocompatibility and in vivo stability of the printed double-network scaffolds through cell encapsulation and animal transplantation.},
keywords = {Advanced (Bio)Manufacturing, Biomaterials, Theory},
pubstate = {published},
tppubtype = {article}
}
Analogous of pixels to two-dimensional pictures, voxels—in the form of either small cubes or spheres—are the basic building blocks of three-dimensional objects. However, precise manipulation of viscoelastic bio-ink voxels in three-dimensional space represents a grand challenge in both soft matter science and biomanufacturing. Here, we present a voxelated bioprinting technology that enables the digital assembly of interpenetrating double-network hydrogel droplets made of polyacrylamide/alginate-based or hyaluronic acid/alginate-based polymers. The hydrogels are crosslinked via additive-free and biofriendly click reaction between a pair of stoichiometrically matched polymers carrying norbornene and tetrazine groups, respectively. We develop theoretical frameworks to describe the crosslinking kinetics and stiffness of the hydrogels, and construct a diagram-of-state to delineate their mechanical properties. Multi-channel print nozzles are developed to allow on-demand mixing of highly viscoelastic bio-inks without significantly impairing cell viability. Further, we showcase the distinctive capability of voxelated bioprinting by creating highly complex three-dimensional structures such as a hollow sphere composed of interconnected yet distinguishable hydrogel particles. Finally, we validate the cytocompatibility and in vivo stability of the printed double-network scaffolds through cell encapsulation and animal transplantation.
2023
3.
Jinchang Zhu, Li-Heng Cai
All-aqueous printing of viscoelastic droplets in yield-stress fluids Journal Article
In: Acta Biomaterialia, vol. 165, no. 2023, pp. 60–71, 2023.
Abstract | Links | Tags: Advanced (Bio)Manufacturing, Bioengineering, Theory
@article{Zhu2023,
title = {All-aqueous printing of viscoelastic droplets in yield-stress fluids},
author = {Jinchang Zhu and Li-Heng Cai},
url = {https://doi.org/10.1016/j.actbio.2022.09.031},
doi = {10.1016/j.actbio.2022.09.031},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {Acta Biomaterialia},
volume = {165},
number = {2023},
pages = {60–71},
publisher = {Elsevier Ltd},
abstract = {All-aqueous printing of viscoelastic droplets (aaPVD) in yield-stress fluids is the core of an emerging voxelated bioprinting technology that enables the digital assembly of spherical bio-ink particles (DASP) to create functional tissue mimics. However, the mechanism of aaPVD is largely unknown. Here, by quantifying the dynamics of the whole printing process in real-time, we identify two parameters critical to aaPVD: (1) acceleration of print nozzle, and (2) droplet/nozzle diameter ratio. Moreover, we distinguish three stages associated with aaPVD: droplet generation, detachment, and relaxation. To generate a droplet of good roundness, the ink should be a highly viscous shear-thinning fluid. Using particle image velocimetry and scaling theory, we establish a universal description for the droplet displacements at various printing conditions. Along the direction of nozzle movement, the droplet displacement is determined by the detachment number, a dimensionless parameter defined as the ratio between the dragging force from the nozzle and the confinement force from the supporting matrix. Perpendicular to the direction of nozzle movement, the droplet displacement is determined by the Oldroyd number, a dimensionless parameter that describes the yielded area of the supporting matrix near the print nozzle. For a relaxed droplet, the droplet tail length is independent of droplet/nozzle diameter ratio but determined by the nozzle acceleration. We conclude that printing droplets of good fidelity requires a relatively large droplet/nozzle diameter ratio and intermediate nozzle accelerations. These ensure that the droplet is more solid-like to not flow with the nozzle to form a tadpole-like morphology and that the confinement force from the yield-stress fluid is large enough to prevent large droplet displacement. Our results provide the knowledge and tools for in situ generating and depositing highly viscoelastic droplets of good roundness at prescribed locations in 3D space, which help establish the foundational science for voxelated bioprinting. Statement of significance: Analogues of pixels to two-dimensional (2D) pictures, voxels – in the form of small cubes or spheres – are the basic units of three-dimensional (3D) objects. All-aqueous printing of viscoelastic droplets (aaPVD) is the core of voxelated bioprinting, an emerging technology that uses spherical bio-ink voxels as building blocks to create 3D tissue mimics. Unlike existing technologies relying on the classic Rayleigh-Plateau instability to generate droplets, aaPVD exploits previously unexplored nonlinear fluid dynamics of complex fluids to precisely manipulate viscoelastic droplets in 3D space. The developed knowledge and tools not only help advance biomanufacturing but also stimulate new research directions in soft matter and complex fluids.},
keywords = {Advanced (Bio)Manufacturing, Bioengineering, Theory},
pubstate = {published},
tppubtype = {article}
}
All-aqueous printing of viscoelastic droplets (aaPVD) in yield-stress fluids is the core of an emerging voxelated bioprinting technology that enables the digital assembly of spherical bio-ink particles (DASP) to create functional tissue mimics. However, the mechanism of aaPVD is largely unknown. Here, by quantifying the dynamics of the whole printing process in real-time, we identify two parameters critical to aaPVD: (1) acceleration of print nozzle, and (2) droplet/nozzle diameter ratio. Moreover, we distinguish three stages associated with aaPVD: droplet generation, detachment, and relaxation. To generate a droplet of good roundness, the ink should be a highly viscous shear-thinning fluid. Using particle image velocimetry and scaling theory, we establish a universal description for the droplet displacements at various printing conditions. Along the direction of nozzle movement, the droplet displacement is determined by the detachment number, a dimensionless parameter defined as the ratio between the dragging force from the nozzle and the confinement force from the supporting matrix. Perpendicular to the direction of nozzle movement, the droplet displacement is determined by the Oldroyd number, a dimensionless parameter that describes the yielded area of the supporting matrix near the print nozzle. For a relaxed droplet, the droplet tail length is independent of droplet/nozzle diameter ratio but determined by the nozzle acceleration. We conclude that printing droplets of good fidelity requires a relatively large droplet/nozzle diameter ratio and intermediate nozzle accelerations. These ensure that the droplet is more solid-like to not flow with the nozzle to form a tadpole-like morphology and that the confinement force from the yield-stress fluid is large enough to prevent large droplet displacement. Our results provide the knowledge and tools for in situ generating and depositing highly viscoelastic droplets of good roundness at prescribed locations in 3D space, which help establish the foundational science for voxelated bioprinting. Statement of significance: Analogues of pixels to two-dimensional (2D) pictures, voxels – in the form of small cubes or spheres – are the basic units of three-dimensional (3D) objects. All-aqueous printing of viscoelastic droplets (aaPVD) is the core of voxelated bioprinting, an emerging technology that uses spherical bio-ink voxels as building blocks to create 3D tissue mimics. Unlike existing technologies relying on the classic Rayleigh-Plateau instability to generate droplets, aaPVD exploits previously unexplored nonlinear fluid dynamics of complex fluids to precisely manipulate viscoelastic droplets in 3D space. The developed knowledge and tools not only help advance biomanufacturing but also stimulate new research directions in soft matter and complex fluids.
2022
2.
Jinchang Zhu, Yi He, Linlin Kong, Zhijian He, Kaylen Y. Kang, Shannon P. Grady, Leander Q. Nguyen, Dong Chen, Yong Wang, Jose Oberholzer, Li-Heng Cai
Digital assembly of spherical viscoelastic bio-ink particles Journal Article
In: Advanced Functional Materials, vol. 32, no. 6, pp. 1–11, 2022.
Abstract | Links | Tags: Advanced (Bio)Manufacturing
@article{Zhu2022,
title = {Digital assembly of spherical viscoelastic bio-ink particles},
author = {Jinchang Zhu and Yi He and Linlin Kong and Zhijian He and Kaylen Y. Kang and Shannon P. Grady and Leander Q. Nguyen and Dong Chen and Yong Wang and Jose Oberholzer and Li-Heng Cai},
doi = {10.1002/adfm.202109004},
year = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {Advanced Functional Materials},
volume = {32},
number = {6},
pages = {1–11},
abstract = {3D bioprinting additively assembles bio-inks to manufacture tissue-mimicking biological constructs, but with the typical building blocks limited to 1D filaments. Here, it is developed a voxelated bioprinting technique for the digital assembly of spherical particles (DASP), which are effectively 0D voxels—the basic unit of 3D structures. It is shown that DASP enables on-demand generation, deposition, and assembly of viscoelastic bio-ink droplets. A two-parameter diagram is developed to outline the viscoelasticity of bio-inks required for printing spherical particles of good fidelity. Moreover, a strategy is developed for engineering bio-inks with independently controllable viscoelasticity and mesh size, two of the most important yet intrinsically coupled physical properties of biomaterials. Using DASP, mechanically robust, multiscale porous scaffolds composed of interconnected yet distinguishable hydrogel particles are created. Finally, it is demonstrated the application of the scaffolds in encapsulating human pancreatic islets for sustained responsive insulin release. Together with the knowledge of bio-ink design, DASP might be used to engineer highly heterogeneous, yet tightly organized tissue constructs for therapeutic applications.},
keywords = {Advanced (Bio)Manufacturing},
pubstate = {published},
tppubtype = {article}
}
3D bioprinting additively assembles bio-inks to manufacture tissue-mimicking biological constructs, but with the typical building blocks limited to 1D filaments. Here, it is developed a voxelated bioprinting technique for the digital assembly of spherical particles (DASP), which are effectively 0D voxels—the basic unit of 3D structures. It is shown that DASP enables on-demand generation, deposition, and assembly of viscoelastic bio-ink droplets. A two-parameter diagram is developed to outline the viscoelasticity of bio-inks required for printing spherical particles of good fidelity. Moreover, a strategy is developed for engineering bio-inks with independently controllable viscoelasticity and mesh size, two of the most important yet intrinsically coupled physical properties of biomaterials. Using DASP, mechanically robust, multiscale porous scaffolds composed of interconnected yet distinguishable hydrogel particles are created. Finally, it is demonstrated the application of the scaffolds in encapsulating human pancreatic islets for sustained responsive insulin release. Together with the knowledge of bio-ink design, DASP might be used to engineer highly heterogeneous, yet tightly organized tissue constructs for therapeutic applications.
2021
1.
Shifeng Nian, Jinchang Zhu, Haozhe Zhang, Zihao Gong, Guillaume Freychet, Mikhail Zhernenkov, Baoxing Xu, Li-Heng Cai
Three-dimensional printable, extremely soft, stretchable, and reversible elastomers from molecular architecture-directed assembly Journal Article
In: Chemistry of Materials, vol. 33, no. 7, pp. 2436–2445, 2021.
Abstract | Links | Tags: Advanced (Bio)Manufacturing, Polymers and Soft Matter
@article{Nian2021,
title = {Three-dimensional printable, extremely soft, stretchable, and reversible elastomers from molecular architecture-directed assembly},
author = {Shifeng Nian and Jinchang Zhu and Haozhe Zhang and Zihao Gong and Guillaume Freychet and Mikhail Zhernenkov and Baoxing Xu and Li-Heng Cai},
doi = {10.1021/acs.chemmater.0c04659},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Chemistry of Materials},
volume = {33},
number = {7},
pages = {2436–2445},
abstract = {3D printing elastomers enables the fabrication of many technologically important structures and devices such as tissue scaffolds, sensors, actuators, and soft robots. However, conventional 3D printable elastomers are intrinsically stiff; moreover, the process of printing often requires external mechanical support and/or post-treatment. Here, we exploit the self-assembly of a responsive linear-bottlebrush-linear triblock copolymer to create stimuli-reversible, extremely soft, and stretchable elastomers and demonstrate their applicability as inks for in situ direct-write printing 3D structures without the aid of external mechanical support or post-treatment. By developing a procedure for controlled synthesis of such architecturally designed block copolymers, we create elastomers with extensibility up to 600% and Young's moduli down to ∼102 Pa, 106 times softer than plastics and more than 102 times softer than all existing 3D printable elastomers. Moreover, the elastomers are thermostable and remain to be solid up to 180 °C, yet they are 100% solvent-reprocessable. Their extreme softness, stretchability, thermostability, and solvent-reprocessability bode well for future applications.},
keywords = {Advanced (Bio)Manufacturing, Polymers and Soft Matter},
pubstate = {published},
tppubtype = {article}
}
3D printing elastomers enables the fabrication of many technologically important structures and devices such as tissue scaffolds, sensors, actuators, and soft robots. However, conventional 3D printable elastomers are intrinsically stiff; moreover, the process of printing often requires external mechanical support and/or post-treatment. Here, we exploit the self-assembly of a responsive linear-bottlebrush-linear triblock copolymer to create stimuli-reversible, extremely soft, and stretchable elastomers and demonstrate their applicability as inks for in situ direct-write printing 3D structures without the aid of external mechanical support or post-treatment. By developing a procedure for controlled synthesis of such architecturally designed block copolymers, we create elastomers with extensibility up to 600% and Young's moduli down to ∼102 Pa, 106 times softer than plastics and more than 102 times softer than all existing 3D printable elastomers. Moreover, the elastomers are thermostable and remain to be solid up to 180 °C, yet they are 100% solvent-reprocessable. Their extreme softness, stretchability, thermostability, and solvent-reprocessability bode well for future applications.