Engineering ellipsoidal cap-like hydrogel particles as building blocks or sacrificial templates for three-dimensional cell culture

Zhang, Weiwei; Huang, Guoman; Ng, Kelvin; Yuan, Jiang; Gao, Bin; Huang, Luqi; Zhou, Jinxiong; Lu, Tian Jian; Xu, Feng

doi:10.1039/c7bm01186e

Cited by 9 publications

(7 citation statements)

References 47 publications

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“…We found that their droplet hanging ability reduces with the decrease of angles between the branch and center shaft as well (Figure 2h). Compared with the traditional open‐pore hanging droplet method, [ 41 ] our bioinspired microstructure platform offers a larger contact area and could hold droplets more firmly, and the preparation process of this rigid structure is convenient with scaling‐up potential.…”

Section: Resultsmentioning

confidence: 99%

Bioinspired Microstructure Platform for Modular Cell‐Laden Microgel Fabrication

Liu

Huang

et al. 2021

Macromolecular Bioscience

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Cell‐laden microgels have attracted increasing interest in various biomedical fields, as living building blocks to construct spatially organized multicellular structures or complex tissue features (e.g., cell spheroids and aligned cells/fibers). Although numerous approaches have been developed to tailor cell‐laden microgels, there is still an unmet need for modular, versatile, convenient, and high‐throughput methods. In this study, as inspired by the phenomena of water droplet manipulation from natural microstructures, a novel platform is developed to manipulate microscale hydrogel droplets and fabricate modular cell‐laden microgels. First, taking antenna‐like trichome as a template, catcher‐like bioinspired microstructures are fabricated and hydrogel droplets are manipulated modularly in a versatile, convenient, and high‐throughput manner, which is compatible with various types of hydrogels (e.g., photo‐cross‐linking, thermal‐cross‐linking, and ion‐cross‐linking). It is demonstrated that this platform can manipulate cell‐laden microgels as modular units, such as two or more cell‐laden microgels on one single catcher‐like structure and different structures on one single chip. The authors also demonstrate the application of this platform on constructing complex tissue features like myocardial fibrosis tissue models to study cardiac fibrosis. The developed platform will be a powerful tool for engineering various in vitro tissue models for widespread biomedical applications.

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Section: Resultsmentioning

confidence: 99%

Bioinspired Microstructure Platform for Modular Cell‐Laden Microgel Fabrication

Liu

Huang

et al. 2021

Macromolecular Bioscience

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“…MSCs have been well-known for their capacity to differentiate desired cell types based on the inducible growth factors. ,, In this study, MSC spheroids were induced to differentiate into chondrocytes using TGF-β3, which has been extensively used in chondrogenesis research in vitro . First, the morphologies of the induced MSC spheroids cultured inside the generated microwell at days 2, 14, and 30 were observed under a microscope (Figure a).…”

Section: Resultsmentioning

confidence: 99%

“…The sacrificial template approach has been wellknown as an effective microfabrication technology method to create cell-friendly scaffolds for tissue engineering owing to its biocompatibility and high-molding effectiveness. 30 Figure 5a illustrates a detailed procedure of microwell fabrication by sacrificing the tadpole-egg-shaped alginate fiber (A−C) and the culture of MSCs to form spheroids inside the microwells (D). To fabricate the microwell, the fiber template was first half-dipped into agarose solution and was melted at 50 °C.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Microfluidic Approach to Generate a Tadpole-Egg-Shaped Alginate Fiber and Its Application in Tissue Engineering

Nguyen

Lee

2019

ACS Biomater. Sci. Eng.

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Herein, we introduce a facile microfluidic technique to produce a hybrid alginate fiber with a tadpoleegg shape. A triple-flow polydimethylsiloxane microfluidic device was constructed to allow the formation of oil droplets inside the alginate stream and was instantaneously gelated with the coaxially adjacent CaCl 2 . The fiber entrapping the uniform oil droplets was dehydrated, leading to the formation of a distinct tadpole-egg-shaped structure. A series of diverse fiber architectures was fabricated in a controlled manner based on the flow rates of the relevant flows. The tadpole-eggshaped alginate fibers were employed as building blocks to create a three-dimensional microwell template for cell cultures. First, the tadpole-egg-shaped alginate fibers containing the oil droplets were half-dipped into a melted agarose solution. After the solidification of the agarose gel, the alginate fibers were degraded by an ethylenediaminetetraacetic acid (EDTA) solution to generate the hemispherical microwells. Mesenchymal stem cells (MSCs) were cultured in the microwells to generate spheroids, which were induced into chondrocytes using transforming growth factor-β3. The formed MSC spheroids exhibited a relatively high ratio of cell viability with more than 95% live cells after 14 days of culture. The success of the chondrogenic differentiation was proven based on staining (Safranin O) and the glycosaminoglycan levels. The latter was significantly higher in spheroids that were induced to form chondrocytes compared to those that were not induced after 21 days of differentiation. Second, we investigated the potential of the tadpole-egg-shaped alginate fibers as microcarriers for applications in drug delivery and implantable technologies. It was revealed that the degradation of the Ca-alginate wall of the hybrid fibers to release the oil droplets required an EDTA solution with a concentration of 500 mM for a 15 min period. This result can be used to further develop the tadpole-egg-shaped alginate fibers as uniform microcarriers with multiple compartments.

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“…156 Furthermore, the inclusion of magnetic nanoparticles enabled cell-laden microgel manipulated by an external magnetic field. 155,156,223 Even though mentioned studies produce microgels with specific geometries, few or no comparisons have been made between geometries on aspects such as cell viability or proliferation. To this end, the effect of varying circularity of methacrylated chitosan hydrogels from spheres to spheroids on the viability of encapsulated L929 cells was studied.…”

Section: Tissue Engineeringmentioning

confidence: 99%