A new cell-laden 3D Alginate-Matrigel hydrogel resembles human breast cancer cell malignant morphology, spread and invasion capability observed “in vivo”

Cavo, Marta; Caria, Marco; Pulsoni, Ilaria; Beltrame, Francesco; Fato, Marco; Scaglione, Silvia

doi:10.1038/s41598-018-23250-4

Cited by 113 publications

(100 citation statements)

References 56 publications

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“…Cell density was observed to increase for up to 7 days of culture and to subsequently plateau at day 14. This observation has been reported previously in the literature [47,48] media. This is notable, since enhanced ALP expression is rarely reported in HBMSCs-laden constructs at early time points (e.g.…”

Section: Discussionsupporting

confidence: 91%

Nanoclay-based 3D printed scaffolds promote vascular ingrowth ex vivo and generate bone mineral tissue in vitro and in vivo

et al. 2020

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Acellular soft hydrogels are not ideal for hard tissue engineering given their poor mechanical stability, however, in combination with cellular components offer significant promise for tissue regeneration. Indeed, nanocomposite bioinks provide an attractive platform to deliver human bone marrow stromal cells (HBMSCs) in three dimensions producing cellladen constructs that aim to facilitate bone repair and functionality. Here we present the in vitro, ex vivo and in vivo investigation of bioprinted HBMSCs encapsulated in a nanoclaybased bioink to produce viable and functional three-dimensional constructs. HBMSC-laden constructs remained viable over 21 days in vitro and immediately functional when conditioned with osteogenic media. 3D scaffolds seeded with human umbilical vein endothelial cells (HUVECs) and loaded with vascular endothelial growth factor (VEGF) implanted ex vivo into a chick chorioallantoic membrane (CAM) model showed integration and vascularisation after 7 days of incubation. In a pre-clinical in vivo application of a nanoclay-based bioink to regenerate skeletal tissue, we demonstrated bone morphogenetic protein-2 (BMP-2) absorbed scaffolds produced extensive mineralisation after 4 weeks (p<0.0001) compared to the drug-free and alginate controls. In addition, HBMSC-laden 3D printed scaffolds were found to significantly (p<0.0001) support bone tissue formation in vivo compared to acellular and cast scaffolds. These studies illustrate the potential of nanoclay-based bioink, to produce viable and functional constructs for clinically relevant skeletal tissue regeneration.

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Section: Discussionsupporting

confidence: 91%

Nanoclay-based 3D printed scaffolds promote vascular ingrowth ex vivo and generate bone mineral tissue in vitro and in vivo

et al. 2020

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“…Latifi et al qualitatively showed that adding collagen type III to glycol chitosan (GC) hydrogel increases the fibroblasts attachment to the surface of the hydrogel 36 . To quantify cell adhesion, previous researchers have used cell morphology such as area, axial ratio, perimeter, major axis, and minor axis 37,38 . The mechanical viscoelastic properties of the hydrogel are also an important factor for adhesion.…”

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confidence: 99%

Carbon nanotubes promote cell migration in hydrogels

Ravanbakhsh

Bao

Mongeau

2020

Sci Rep

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injectable hydrogels are increasingly used for in situ tissue regeneration and wound healing. ideally, an injectable implant should promote the recruitment of cells from the surrounding native tissue and allow cells to migrate freely as they generate a new extracellular matrix network. nanocomposite hydrogels such as carbon nanotube (cnt)-loaded hydrogels have been hypothesized to promote cell recruitment and cell migration relative to unloaded ones. to investigate this, cnt-glycol chitosan hydrogels were synthesized and studied. Chemoattractant-induced cell migration was studied using a modified Boyden Chamber experiment. Migrated cells were counted using flow cytometry. Cell adhesion was inferred from the morphology of the cells via an image segmentation method. cell migration and recruitment results confirmed that small concentrations of CNT significantly increase cell migration in hydrogels, thereby accelerating tissue regeneration and wound healing in situations where there is insufficient migration in the unloaded matrix. Hydrogels offer many advantages for biomedical applications due to their unique properties, in particular, their biocompatibility, biodegradation rate, mechanical stiffness, hydrophilicity, and porosity 1,2. Nanocomposite hydrogels have the potential to further improve upon these properties through the addition of nanoparticles to pure hydrogels. Such nanocomposite hydrogels have been reported to increase three-and four-dimensional printability, stiffness tunability, and electrical conductivity 3-9. For tissue engineering applications, composite hydrogels should allow sufficient cell adhesion and cell migration within its network. Such cell-biomaterial interaction is known to accelerate wound healing and tissue regeneration in the target region 10,11. Collagen, fibrin, fibronectin, nanoclays, cellulose nanocrystals, cellulose nanowhiskers, graphene oxide, and carbon nanotubes (CNTs) are among the many functional reinforcements available for fabricating bionanocomposite hydrogels 7,12-16. In our previous work, we found that the addition of CNTs to a glycol-chitosan matrix alters gelation time, porosity, and storage modulus 17. Since their discovery in 1991 by Iijima 18 , CNTs have been broadly used in biomedical applications. The CNTs can firmly attach to proteins and receptors on the cell membrane. The adherence between CNTs and cells is important. Firstly, single-walled carbon nanotubes (SWCNTs) may be employed for the purpose of drug delivery 19. Gangrade et al. took advantage of the thermal properties of the SWCNTs to obtain a temperature-dependent release of preloaded doxorubicin 20. Secondly, multiwalled carbon nanotubes (MWCNTs), which due to their size are more practical for tissue engineering applications, can be used as focal adhesion sites to enhance cell adhesion for anchorage-dependent cells such as fibroblasts 21,22. The latter may lead to an increased cell migration rate in CNT-loaded composite hydrogels. The larger diameter of MWCNTs with respect to SWCNTs approximates the p...

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“…There is a growing appreciation that cells grown in vitro , on rigid polystyrene tissue culture surfaces, behave very differently than cells in vivo , and that the stiffness of the surface upon which cells are grown can have profound epigenetic effects on cells that influence their phenotype [80, 81]. In addition, many investigators have observed that morphologies of neuronal cells are strikingly more similar to those expressed in vivo in 3D vs. 2D culture [22, 23, 82, 83]. Thus, the use of 3D cell culture models for AD drug development may lead to a more positive correlation between successes in vitro and successes in clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Collagen hydrogel confinement of amyloid-βaccelerates aggregation and reduces cytotoxic effects

Simpson¹,

Szeto²,

Boukari

et al. 2019

Preprint

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18Alzheimer's disease (AD) is the most common form of dementia and is associated with the 19 accumulation of amyloid-β (Aβ), a peptide whose aggregation has been associated with neurotoxicity. 20 Drugs targeting Aβ have shown great promise in 2D in vitro models and mouse models, yet preclinical 21 and clinical trials for AD have been highly disappointing. We propose that current in vitro culture 22 systems for discovering and developing AD drugs have significant limitations; specifically, that Aβ 23 aggregation is vastly different in these 2D cultures carried out on flat plastic or glass substrates vs. in a 24 3D environment, such as brain tissue, where Aβ confinement very likely alters aggregation kinetics and 25 thermodynamics. In this work, we identified attenuation of Aβ cytotoxicity in 3D hydrogel culture 26 compared to 2D cell culture. We investigated Aβ structure and aggregation in solution vs. hydrogel using 27Transmission Electron Microscopy (TEM), Fluorescence Correlation Spectroscopy (FCS), and Thioflavin T 28 (ThT) assays. Our results reveal that the equilibrium is shifted to stable β-sheet aggregates in hydrogels 29 and away from the relatively unstable/unstructured presumed toxic oligomeric Aβ species in solution. 30 Volume exclusion imparted by hydrogel confinement stabilizes unfolded, presumably toxic species, 31 promoting stable extended β-sheet fibrils. These results, taken together with the many recent reports 32 that 3D hydrogel cell cultures enable cell morphologies and epigenetic changes that are more similar to 33 cells in vivo compared to 2D cultures, strongly suggest that AD drugs should be tested in 3D culture 34 systems as a step along the development pathway towards new, more effective therapeutics. 35 36

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A new cell-laden 3D Alginate-Matrigel hydrogel resembles human breast cancer cell malignant morphology, spread and invasion capability observed “in vivo”

Cited by 113 publications

References 56 publications

Nanoclay-based 3D printed scaffolds promote vascular ingrowth ex vivo and generate bone mineral tissue in vitro and in vivo

Nanoclay-based 3D printed scaffolds promote vascular ingrowth ex vivo and generate bone mineral tissue in vitro and in vivo

Carbon nanotubes promote cell migration in hydrogels

Collagen hydrogel confinement of amyloid-βaccelerates aggregation and reduces cytotoxic effects

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