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.
2024
4.
Zhi Jian He, Catherine Chu, Riley Dickson, Kenichi Okuda, Li-Heng Cai
A gel-coated air-liquid-interface culture system with tunable substrate stiffness matching healthy and diseased lung tissues Journal Article
In: American journal of physiology. Lung cellular and molecular physiology, vol. 326, no. 3, pp. L292–L302, 2024.
Abstract | Links | Tags: Bioengineering, Biomaterials
@article{He2024,
title = {A gel-coated air-liquid-interface culture system with tunable substrate stiffness matching healthy and diseased lung tissues},
author = {Zhi Jian He and Catherine Chu and Riley Dickson and Kenichi Okuda and Li-Heng Cai},
url = {https://doi.org/10.1152/ajplung.00153.2023},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {American journal of physiology. Lung cellular and molecular physiology},
volume = {326},
number = {3},
pages = {L292–L302},
abstract = {Since its invention in the late 1980s, the air-liquid-interface (ALI) culture system has been the standard in vitro model for studying human airway biology and pulmonary diseases. However, in a conventional ALI system, cells are cultured on a porous plastic membrane that is much stiffer than human airway tissues. Here, we develop a gel-ALI culture system by simply coating the plastic membrane with a thin layer of hydrogel with tunable stiffness matching that of healthy and fibrotic airway tissues. We determine the optimum gel thickness that does not impair the transport of nutrients and biomolecules essential to cell growth. We show that the gel-ALI system allows human bronchial epithelial cells (HBECs) to proliferate and differentiate into pseudostratified epithelium. Furthermore, we discover that HBECs migrate significantly faster on hydrogel substrates with stiffness matching that of fibrotic lung tissues, highlighting the importance of mechanical cues in human airway remodeling. The developed gel-ALI system provides a facile approach to studying the effects of mechanical cues in human airway biology and in modeling pulmonary diseases.},
keywords = {Bioengineering, Biomaterials},
pubstate = {published},
tppubtype = {article}
}
Since its invention in the late 1980s, the air-liquid-interface (ALI) culture system has been the standard in vitro model for studying human airway biology and pulmonary diseases. However, in a conventional ALI system, cells are cultured on a porous plastic membrane that is much stiffer than human airway tissues. Here, we develop a gel-ALI culture system by simply coating the plastic membrane with a thin layer of hydrogel with tunable stiffness matching that of healthy and fibrotic airway tissues. We determine the optimum gel thickness that does not impair the transport of nutrients and biomolecules essential to cell growth. We show that the gel-ALI system allows human bronchial epithelial cells (HBECs) to proliferate and differentiate into pseudostratified epithelium. Furthermore, we discover that HBECs migrate significantly faster on hydrogel substrates with stiffness matching that of fibrotic lung tissues, highlighting the importance of mechanical cues in human airway remodeling. The developed gel-ALI system provides a facile approach to studying the effects of mechanical cues in human airway biology and in modeling pulmonary diseases.
3.
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.
2.
Zhi Jian He, Baiqiang Huang,, Li Heng Cai
Bottlebrush polyethylene glycol nanocarriers translocate across human airway epithelium via molecular architecture-enhanced endocytosis Journal Article
In: ACS Nano, vol. 18, iss. 27, pp. 17586–17599, 2024.
Abstract | Links | Tags: Bioengineering, Biomaterials
@article{He2024a,
title = {Bottlebrush polyethylene glycol nanocarriers translocate across human airway epithelium via molecular architecture-enhanced endocytosis},
author = {Zhi Jian He, Baiqiang Huang, and Li Heng Cai},
doi = {10.1021/acsnano.4c01983},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {ACS Nano},
volume = {18},
issue = {27},
pages = {17586–17599},
abstract = {Pulmonary drug delivery is critical for the treatment of respiratory diseases. However, the human airway surface presents multiple barriers to efficient drug delivery. Here, we report a bottlebrush poly(ethylene glycol) (PEG-BB) nanocarrier that can translocate across all barriers within the human airway surface. Guided by a molecular theory, we design a PEG-BB molecule consisting of a linear backbone densely grafted by many (∼1000) low molecular weight (∼1000 g/mol) polyethylene glycol (PEG) chains; this results in a highly anisotropic, wormlike nanocarrier featuring a contour length of ∼250 nm, a cross-section of ∼20 nm, and a hydrodynamic diameter of ∼40 nm. Using the classic air-liquid-interface culture system to recapitulate essential biological features of the human airway surface, we show that PEG-BB rapidly penetrates through endogenous airway mucus and periciliary brush layer (mesh size of 20-40 nm) to be internalized by cells across the whole epithelium. By quantifying the cellular uptake of polymeric carriers of various molecular architectures and manipulating cell proliferation and endocytosis pathways, we show that the translocation of PEG-BB across the epithelium is driven by bottlebrush architecture-enhanced endocytosis. Our results demonstrate that large, wormlike bottlebrush PEG polymers, if properly designed, can be used as a carrier for pulmonary and mucosal drug delivery.},
keywords = {Bioengineering, Biomaterials},
pubstate = {published},
tppubtype = {article}
}
Pulmonary drug delivery is critical for the treatment of respiratory diseases. However, the human airway surface presents multiple barriers to efficient drug delivery. Here, we report a bottlebrush poly(ethylene glycol) (PEG-BB) nanocarrier that can translocate across all barriers within the human airway surface. Guided by a molecular theory, we design a PEG-BB molecule consisting of a linear backbone densely grafted by many (∼1000) low molecular weight (∼1000 g/mol) polyethylene glycol (PEG) chains; this results in a highly anisotropic, wormlike nanocarrier featuring a contour length of ∼250 nm, a cross-section of ∼20 nm, and a hydrodynamic diameter of ∼40 nm. Using the classic air-liquid-interface culture system to recapitulate essential biological features of the human airway surface, we show that PEG-BB rapidly penetrates through endogenous airway mucus and periciliary brush layer (mesh size of 20-40 nm) to be internalized by cells across the whole epithelium. By quantifying the cellular uptake of polymeric carriers of various molecular architectures and manipulating cell proliferation and endocytosis pathways, we show that the translocation of PEG-BB across the epithelium is driven by bottlebrush architecture-enhanced endocytosis. Our results demonstrate that large, wormlike bottlebrush PEG polymers, if properly designed, can be used as a carrier for pulmonary and mucosal drug delivery.
2016
1.
Liyuan Zhang, Li-Heng Cai, Philipp S. Lienemann, Torsten Rossow, Ingmar Polenz, Queralt Vallmajo-Martin, Martin Ehrbar, Hui Na, David J. Mooney, David A. Weitz
One-step microfluidic fabrication of polyelectrolyte microcapsules in aqueous conditions for protein release Journal Article
In: Angewandte Chemie – International Edition, vol. 55, no. 43, pp. 13470–13474, 2016.
Abstract | Links | Tags: Bioengineering, Biomaterials
@article{Zhang2016,
title = {One-step microfluidic fabrication of polyelectrolyte microcapsules in aqueous conditions for protein release},
author = {Liyuan Zhang and Li-Heng Cai and Philipp S. Lienemann and Torsten Rossow and Ingmar Polenz and Queralt Vallmajo-Martin and Martin Ehrbar and Hui Na and David J. Mooney and David A. Weitz},
doi = {10.1002/anie.201606960},
year = {2016},
date = {2016-01-01},
urldate = {2016-01-01},
journal = {Angewandte Chemie - International Edition},
volume = {55},
number = {43},
pages = {13470–13474},
abstract = {We report a microfluidic approach for one-step fabrication of polyelectrolyte microcapsules in aqueous conditions. Using two immiscible aqueous polymer solutions, we generate transient water-in-water-in-water double emulsion droplets and use them as templates to fabricate polyelectrolyte microcapsules. The capsule shell is formed by the complexation of oppositely charged polyelectrolytes at the immiscible interface. We find that attractive electrostatic interactions can significantly prolong the release of charged molecules. Moreover, we demonstrate the application of these microcapsules in encapsulation and release of proteins without impairing their biological activities. Our platform should benefit a wide range of applications that require encapsulation and sustained release of molecules in aqueous environments.},
keywords = {Bioengineering, Biomaterials},
pubstate = {published},
tppubtype = {article}
}
We report a microfluidic approach for one-step fabrication of polyelectrolyte microcapsules in aqueous conditions. Using two immiscible aqueous polymer solutions, we generate transient water-in-water-in-water double emulsion droplets and use them as templates to fabricate polyelectrolyte microcapsules. The capsule shell is formed by the complexation of oppositely charged polyelectrolytes at the immiscible interface. We find that attractive electrostatic interactions can significantly prolong the release of charged molecules. Moreover, we demonstrate the application of these microcapsules in encapsulation and release of proteins without impairing their biological activities. Our platform should benefit a wide range of applications that require encapsulation and sustained release of molecules in aqueous environments.