“All-in-one” zwitterionic granular hydrogel bioink for stem cell spheroids production and 3D bioprinting

Zhang, Jiahui; Wei, Xin; Qin, Yechi; Hong, Yu‐Hao; Xiahou, Zijie; Zhang, Kunxi; Fu, Peiliang; Yin, Jingbo

doi:10.1016/j.cej.2021.132713

Cited by 23 publications

(21 citation statements)

References 45 publications

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“…Centrifuging is often used to pack microgels into a granular scaffold, where varying centrifuge speed can influence the degree of microgel packing. ,, To further increase packing between microgel particles, granular hydrogels can be fabricated using vacuum-driven filtration, where an aqueous suspension of microgels is added to a membrane filter with submicrometer pore sizes, and vacuum force is used to remove interstitial fluid. − To avoid the need for external forces (i.e., centrifugal, vacuum pressure), microgel packing by gravitational settling can also be used . Lastly, microgels can be dehydrated after fabrication, and the aqueous resuspension of dried microgel particles can be used for granular hydrogel assembly. ,− …”

Section: Introductionmentioning

confidence: 99%

“…The microscale porosity present within the interstitial space between microgels is another major advantage of granular hydrogel biomaterials. Granular hydrogels have been explored for in vitro cell and spheroid culture. ,,,− Often, cells or spheroids are placed in the interstitial space, using the microgel surfaces as a substrate for invasion, proliferation, and outgrowth (Figure c). Here too, granular hydrogels are often stabilized by interparticle cross-linking to create scaffolds with structural integrity for in vitro studies.…”

Section: Introductionmentioning

confidence: 99%

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Methods to Characterize Granular Hydrogel Rheological Properties, Porosity, and Cell Invasion

Qazi

Muir

Burdick

2022

ACS Biomater. Sci. Eng.

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Granular hydrogels are formed through the packing of hydrogel microparticles and are emerging for various biomedical applications, including as inks for 3D printing, substrates to study cell−matrix interactions, and injectable scaffolds for tissue repair. Granular hydrogels are suited for these applications because of their unique properties including inherent porosity, shear-thinning and self-healing behavior, and tunable design. The characterization of their material properties and biological response involves technical considerations that are unique to modular systems like granular hydrogels. Here, we describe detailed methods that can be used to quantitatively characterize the rheological behavior and porosity of granular hydrogels using reagents, tools, and equipment that are typically available in biomedical engineering laboratories. In addition, we detail methods for 3D cell invasion assays using multicellular spheroids embedded within granular hydrogels and describe steps to quantify features of cell outgrowth (e.g., endothelial cell sprouting) using standard image processing software. To illustrate these methods, we provide examples where features of granular hydrogels such as the size of hydrogel microparticles and their extent of packing during granular hydrogel formation are modulated. Our intent with this resource is to increase accessibility to granular hydrogel technology and to facilitate the investigation of granular hydrogels for biomedical applications.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Methods to Characterize Granular Hydrogel Rheological Properties, Porosity, and Cell Invasion

Qazi

Muir

Burdick

2022

ACS Biomater. Sci. Eng.

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“…To improve the use of 3D printing and bioinks in tissue regeneration [ 88 ], nanogels encapsulating cell clusters can be integrated into 3D printed gel models. Compared to the traditional bioinks, the nanogel can prevent unexpected cell behaviors (e.g., aggregation, dispersion, and sedimentation), and fabricate 3D models with higher precision and less cell damages during the printing process [ 89 , 90 ]. Laser ablation (e.g., multi-photon ablation) and electrospun techniques are also conducive to fabricate sophisticated LN biomaterial models as well as improved reproducibility and larger-scale applications [ 91 ].…”

Section: Advanced Biomaterials Approaches For Mimicking and Studying ...mentioning

confidence: 99%

Integrative lymph node-mimicking models created with biomaterials and computational tools to study the immune system

Shou¹,

Johnson²,

Quek³

et al. 2022

Materials Today Bio

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“…Alternatively, the emerging densely packed or jammed microgels exhibit a promising prospect as a universal 3D printing bioink. − In a packed or jammed state, microgels physically contact, support, and squeeze with each other, appearing like bulk hydrogels . However, since the intermicrogel interactions are much weaker compared to the covalent bonding inside microgels, they can yield to flow when external forces overcome the intermicrogel friction.…”

Section: Introductionmentioning

confidence: 99%

Assembling Microgels via Dynamic Cross-Linking Reaction Improves Printability, Microporosity, Tissue-Adhesion, and Self-Healing of Microgel Bioink for Extrusion Bioprinting

Feng

et al. 2022

ACS Appl. Mater. Interfaces

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Extrusion bioprinting has been widely used to fabricate complicated and heterogeneous constructs for tissue engineering and regenerative medicine. Despite the remarkable progress acquired so far, the exploration of qualified bioinks is still challenging, mainly due to the conflicting requirements on the printability/shape-fidelity and cell viability. Herein, a new strategy is proposed to formulate a dynamic cross-linked microgel assembly (DC-MA) bioink, which can achieve both high printability/shapefidelity and high cell viability by strengthening intermicrogel interactions through dynamic covalent bonds while still maintaining the relatively low mechanical modulus of microgels. As a proofof-concept, microgels are prepared by cross-linking hyaluronic acid modified with methacrylate and phenylboric acid groups (HAMA-PBA) and methacrylated gelatin (GelMA) via droplet-based microfluidics, followed by assembling into DC-MA bioink with a dynamic cross-linker (dopamine-modified hyaluronic acid, HA-DA). As a result, 2D and 3D constructs with high shape-fidelity can be printed without post-treatment, and the encapsulated L929 cells exhibit high cell viability after extrusion. Moreover, the addition of the dynamic cross-linker (HA-DA) also improves the microporosity, tissue-adhesion, and self-healing of the DC-MA bioink, which is very beneficial for tissue engineering and regenerative medicine applications including wound healing. We believe the present work sheds a new light on designing new bioinks for extrusion bioprinting.

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“All-in-one” zwitterionic granular hydrogel bioink for stem cell spheroids production and 3D bioprinting

Cited by 23 publications

References 45 publications

Methods to Characterize Granular Hydrogel Rheological Properties, Porosity, and Cell Invasion

Methods to Characterize Granular Hydrogel Rheological Properties, Porosity, and Cell Invasion

Integrative lymph node-mimicking models created with biomaterials and computational tools to study the immune system

Assembling Microgels via Dynamic Cross-Linking Reaction Improves Printability, Microporosity, Tissue-Adhesion, and Self-Healing of Microgel Bioink for Extrusion Bioprinting

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