Advanced Bottom‐Up Engineering of Living Architectures

Gaspar, Vítor M.; Lavrador, Pedro; Borges, João; Oliveira, Mariana B.; Mano, João F.

doi:10.1002/adma.201903975

Cited by 143 publications

(134 citation statements)

References 439 publications

(538 reference statements)

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“…Material development to allow diverse nanoscale presentation of bioactive ligand can unravel complex cellular responses to diverse ligand nano geometry, involving integrin‐ligand binding that occurs in the nanoscale. [ 7,8 ] Various spatial presentation of RGD‐bearing homogeneous nanoparticles [ 9,10 ] has been reported to modulate cell adhesion [ 11 ] by regulating the density and inter‐nanoparticle spacing, [ 12–15 ] ordering and disordering, [ 13 ] dynamic changes in nanospacing, [ 14,16 ] local and global density, [ 12 ] nanospacing within micropatterns, [ 17–19 ] and clustering. [ 20 ] Our own studies showed that magnetically controlled sliding [ 21 ] and macroscale motion, [ 22 ] and self‐assembly [ 23 ] of RGD‐bearing nanoparticles [ 24 ] dynamically regulate cellular adhesion.…”

Section: Methodsmentioning

confidence: 99%

Independent Tuning of Nano‐Ligand Frequency and Sequences Regulates the Adhesion and Differentiation of Stem Cells

et al. 2020

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Natural extracellular matrix (ECM) can regulate the interactions between cells and ligands by exhibiting heterogeneous nano-sequences periodically displaying adhesive ligands, such as RGD ligand in vivo. [1,2] Cell-adhesive ECM proteins, such as fibronectin, vitronectin, and collagen, were shown to form periodically sequenced RGD ligand-bearing nanostructures (67-100 nm). [1] Periodic structure in reflectance was also observed from native tissues. [2] The ligation of integrin with adhesive ligand mediates the assembly of cytoskeletal actin filaments and focal adhesion (FA) complexes to activate mechanosensing signaling pathways that can regulate cellular differentiation. [3,4] Strategically developing materials with heterogeneously sequenced ligand nanostructures can emulate ECM [5] microenvironment to help elucidate the interactions between cells and nano-ligands with tunable frequency and sequences. This can effectively regulate diverse cellular adhesion and functionality in vivo, such as FA, mechanosensing, and differentiation of stem cells. [6] The native extracellular matrix (ECM) can exhibit heterogeneous nanosequences periodically displaying ligands to regulate complex cell-material interactions in vivo. Herein, an ECM-emulating heterogeneous barcoding system, including ligand-bearing Au and ligand-free Fe nano-segments, is developed to independently present tunable frequency and sequences in nano-segments of cell-adhesive RGD ligand. Specifically, similar exposed surface areas of total Fe and Au nano-segments are designed. Fe segments are used for substrate coupling of nanobarcodes and as ligand-free nanosegments and Au segments for ligand coating while maintaining both nanoscale (local) and macroscale (total) ligand density constant in all groups. Low nano-ligand frequency in the same sequences and terminally sequenced nano-ligands at the same frequency independently facilitate focal adhesion and mechanosensing of stem cells, which are collectively effective both in vitro and in vivo, thereby inducing stem cell differentiation. The Fe/RGD-Au nanobarcode implants exhibit high stability and no local and systemic toxicity in various tissues and organs in vivo. This work sheds novel insight into designing biomaterials with heterogeneous nano-ligand sequences at terminal sides and/or low frequency to facilitate cellular adhesion. Tuning the electrodeposition conditions can allow synthesis of unlimited combinations of ligand nano-sequences and frequencies, magnetic elements, and bioactive ligands to remotely regulate numerous host cells in vivo.

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Section: Methodsmentioning

confidence: 99%

Independent Tuning of Nano‐Ligand Frequency and Sequences Regulates the Adhesion and Differentiation of Stem Cells

et al. 2020

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“…[44] Although multiorgan-on-a-chip techniques provided great benefits in the simulation of human bodily responses, bottom-up tissue engineering with a combination of cell-biomaterials constructs for scaling up microtissues or organoids remains challenging. [45] Taken together, development of a bioprinting technique has the capability to fabricate vascularized multiscale tissue constructs. These bioprinting techniques can be used in conjunction with other emerging biotechnologies to aid development of alternative animal testing and contribute to the success of clinical trials.…”

Section: Introductionmentioning

confidence: 99%

“…[ 44 ] Although multiorgan‐on‐a‐chip techniques provided great benefits in the simulation of human bodily responses, bottom‐up tissue engineering with a combination of cell–biomaterials constructs for scaling up microtissues or organoids remains challenging. [ 45 ]…”

Section: Introductionmentioning

confidence: 99%

Bioprinting of Multiscaled Hepatic Lobules within a Highly Vascularized Construct

Kang¹,

Gao

et al. 2020

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111

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Highly vascularized complex liver tissue is generally divided into lobes, lobules, hepatocytes, and sinusoids, which can be viewed under different types of lens from the micro‐ to macro‐scale. To engineer multiscaled heterogeneous tissues, a sophisticated and rapid tissue engineering approach is required, such as advanced 3D bioprinting. In this study, a preset extrusion bioprinting technique, which can create heterogeneous, multicellular, and multimaterial structures simultaneously, is utilized for creating a hepatic lobule (≈1 mm) array. The fabricated hepatic lobules include hepatic cells, endothelial cells, and a lumen. The endothelial cells surround the hepatic cells, the exterior of the lobules, the lumen, and finally, become interconnected with each other. Compared to hepatic cell/endothelial cell mixtures, the fabricated hepatic lobule shows higher albumin secretion, urea production, and albumin, MRP2, and CD31 protein levels, as well as, cytochrome P450 enzyme activity. It is found that each cell type with spatial cell patterning in bioink accelerates cellular organization, which could preserve structural integrity and improve cellular functions. In conclusion, preset extruded hepatic lobules within a highly vascularized construct are successfully constructed, enabling both micro‐ and macro‐scale tissue fabrication, which can support the creation of large 3D tissue constructs for multiscale tissue engineering.

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“…The motivation and the demand for building living tissues or organs lead to loads of technology innovations in biomedical engineering. [1][2][3] As a cellular-assembly method, three-dimensional (3D) bioprinting has been extensively used in the fabrication of cell-laden 3D scaffolds to replicate the tissue architectures. [4][5][6][7][8][9] The principle of the 3D bioprinting can be defined as the placement of living cells within biomaterials into preprogrammed structures and geometries using automated fabrication processes.…”

Section: Introductionmentioning

confidence: 99%

Granular hydrogels for 3D bioprinting applications

Cheng

Zhang

Liu

et al. 2020

VIEW

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Granular hydrogels are the conglomerations of micrometer‐sized hydrogel particles that have recently become promising in tissue growth and three‐dimensional (3D) bioprinting. Recent advances in the use of jamming transition of granular hydrogels represent a potential paradigm shift in the extrusion‐based 3D bioprinting. These dynamic granular hydrogels are shear thinning and self‐healing, enable higher printing performance, and the creation of better physiological conditions for heterocellular constructs. Here, we review the current efforts to explore materials to produce granular hydrogels with novel functional properties, focusing on the granular hydrogels that can be used for supporting baths and bioinks in the extrusion‐based 3D bioprinting. The recent advances, benefits, and challenges in this emerging area are highlighted.

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Advanced Bottom‐Up Engineering of Living Architectures

Cited by 143 publications

References 439 publications

Independent Tuning of Nano‐Ligand Frequency and Sequences Regulates the Adhesion and Differentiation of Stem Cells

Independent Tuning of Nano‐Ligand Frequency and Sequences Regulates the Adhesion and Differentiation of Stem Cells

Bioprinting of Multiscaled Hepatic Lobules within a Highly Vascularized Construct

Granular hydrogels for 3D bioprinting applications

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