Assembling Living Building Blocks to Engineer Complex Tissues

Ouyang, Liliang; Armstrong, James R.; Salmerón‐Sánchez, Manuel; Stevens, Molly M.

doi:10.1002/adfm.201909009

Cited by 98 publications

(93 citation statements)

References 292 publications

(553 reference statements)

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“…The emergence of three-dimensional (3D) bioprinting has opened up new avenues for engineering in vitro living systems that can be used in tissue regeneration, biological modeling, and cell-based diagnostics ( 1 , 2 ). 3D bioprinting is based on the free-form fabrication of biomaterials into customized geometries informed by digital design.…”

Section: Introductionmentioning

confidence: 99%

“…3D bioprinting is based on the free-form fabrication of biomaterials into customized geometries informed by digital design. The most common modality for tissue fabrication is extrusion bioprinting, in which living constructs are additively manufactured via layer-by-layer deposition of cellularized bioinks ( 1 , 3 ). The design of bioinks is a central topic in this field-formulations rarely have both the physicochemical properties required for the 3D printing process and the physicochemical cues to meet the biological needs of the encapsulated cells.…”

Section: Introductionmentioning

confidence: 99%

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Expanding and optimizing 3D bioprinting capabilities using complementary network bioinks

et al. 2020

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A major challenge in three-dimensional (3D) bioprinting is the limited number of bioinks that fulfill the physicochemical requirements of printing while also providing a desirable environment for encapsulated cells. Here, we address this limitation by temporarily stabilizing bioinks with a complementary thermo-reversible gelatin network. This strategy enables the effective printing of biomaterials that would typically not meet printing requirements, with instrument parameters and structural output largely independent of the base biomaterial. This approach is demonstrated across a library of photocrosslinkable bioinks derived from natural and synthetic polymers, including gelatin, hyaluronic acid, chondroitin sulfate, dextran, alginate, chitosan, heparin, and poly(ethylene glycol). A range of complex and heterogeneous structures are printed, including soft hydrogel constructs supporting the 3D culture of astrocytes. This highly generalizable methodology expands the palette of available bioinks, allowing the biofabrication of constructs optimized to meet the biological requirements of cell culture and tissue engineering.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expanding and optimizing 3D bioprinting capabilities using complementary network bioinks

et al. 2020

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“…This need has fostered the development of a wide range of biofabrication techniques, where the term biofabrication indicates "the automated generation of structurally organized, biologically functional products from living cells, bioactive molecules, biomaterials, cell aggregates such as microtissues or hybrid cellmaterial constructs through bioprinting or bioassembly." [216,217] Hydrogels are used as the biomaterial component in many biofabrication strategies, as their phase behavior and trigger mechanisms enable flexible manufacturing methods. A relatively simple hydrogel biofabrication strategy is micromolding, in which a hydrogel precursor solution is deposited into a mold, crosslinked, and then demolded.…”

Section: (12 Of 22)mentioning

confidence: 99%

Tailoring Gelation Mechanisms for Advanced Hydrogel Applications

Nele

Wojciechowski

Armstrong

et al. 2020

Adv Funct Materials

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Hydrogels are one of the most commonly explored classes of biomaterials. Their chemical and structural versatility has enabled their use across a wide range of applications, including tissue engineering, drug delivery, and cell culture. Hydrogels form upon a sol-gel transition, which can be elicited by different triggers designed to enable precise control over hydrogelation kinetics and hydrogel structure. The chosen hydrogelation trigger and chemistry can have a profound effect on the success of the targeted application. In this Progress Report, a critical overview of recent advances in hydrogel design is presented, with a focus on the available strategies used to trigger the formation of hydrogel networks (e.g., temperature, light, ultrasound). These triggers are presented within a new classification system, and their suitability for six key hydrogel-based applications is assessed. This Progress Report is intended to guide trigger selection for new hydrogel applications and inspire the rational design of new hydrogelation trigger mechanisms.

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“…In order to closely mimic complex tissues in vitro, artificial multicellular systems are created from different cell types in spatially ordered structures or well‐defined geometries in a 3D microenvironment. [ 1–3 ] These systems can be built from building blocks [ 4–7 ] such as cell sheets, [ 8 ] cell‐laden microgels, [ 5 ] cell spheroids, [ 9 ] and organoids. [ 10,11 ] Precise control of cellular composition and spatial distribution of building blocks within artificial multicellular systems allows for reconstitution of native tissues in their healthy and disease state in vitro.…”

Section: Figurementioning

confidence: 99%

Assembly of Multi‐Spheroid Cellular Architectures by Programmable Droplet Merging

et al. 2020

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Reproduction of native tissues in vitro is important as a tool, as it both enables investigation of fundamental biological processes, and drug and toxicity screenings. In order to closely mimic complex tissues in vitro, artificial multicellular systems are created from different cell types in spatially ordered structures or welldefined geometries in a 3D microenvironment. [1-3] These systems can be built from building blocks [4-7] such as cell sheets, [8] cell-laden microgels, [5] cell spheroids, [9] and organoids. [10,11] Precise control of cellular composition and spatial distribution of building blocks within artificial multicellular systems allows for reconstitution of native tissues in their healthy and disease state in vitro. [12] There are a number of methodologies developed for fabrication of complex 3D cell systems in vitro. [3-7,13,14] Directed assembly allows manual positioning or stacking building blocks to form 3D architectures. [15,16] Birey et al. applied this method for fusion of two forebrain organoids in order to mimic the human brain development and demonstrate inter-neuronal migration. [15] The method of directed assembly is, however, manual and not compatible with high throughput. Remote assembly, such as, acoustic node, [14,17] magnetic cell levitation, [13,18] optical tweezers, [19] or laser-guided direct writing, [20] can achieve assembly of cells or spheroids against gravity or viscous forces. Chen et al. demonstrated the assembly of hepatic organoids by an acoustic node technique, and the technique was able to achieve formation of bile canaliculi networks resembling native hepatic tissue. [17] Souza et al. used magnetic cell levitation to manipulate a glioblastoma cell spheroid, and a human astrocyte spheroid in order to create a cell invasion model. [18] These methods depend on sophisticated equipment, paramagnetic media, or introduce a risk of laser-induced cell damage. Another common strategy used to fabricate multicellular architecture is assembly of cell-laden hydrogels or microgels, [5,21,22] or cell seeding on scaffolds. [7,23] However, these biomaterial-based methods failed to provide high cell packing density. The use of artificial scaffolds or gel matrices additionally lead to disadvantages for constructing 3D tissue models due to their influence on cell-cell interactions, autocrine, and paracrine signaling. 3D printing [3] is a promising method for designing and achieving multicellular architectures, but it is relatively slow, not always compatible with high throughput and relies on printable bio-inks for maintaining 3D structure and cell viability. Artificial multicellular systems are gaining importance in the field of tissue engineering and regenerative medicine. Reconstruction of complex tissue architectures in vitro is nevertheless challenging, and methods permitting controllable and high-throughput fabrication of complex multicellular architectures are needed. Here, a facile and high-throughput method is developed based on a tunable droplet-fusion technique, allowing prog...

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Assembling Living Building Blocks to Engineer Complex Tissues

Cited by 98 publications

References 292 publications

Expanding and optimizing 3D bioprinting capabilities using complementary network bioinks

Expanding and optimizing 3D bioprinting capabilities using complementary network bioinks

Tailoring Gelation Mechanisms for Advanced Hydrogel Applications

Assembly of Multi‐Spheroid Cellular Architectures by Programmable Droplet Merging

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