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| Open Access3D microfluidic liver cultures as a physiological preclinical tool for hepatitis B virus infection
Long-term in vitro models for hepatitis B virus (HBV) infection are important to understand this infection, but are lacking. Here the authors develop a microfluidic primary human hepatocyte organoid culture system that can be maintained over 40 days and recapitulates all of the steps of the HBV life cycle.
- A. M. Ortega-Prieto
- , J. K. Skelton
- & M. Dorner
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Article
| Open AccessEngineering human pluripotent stem cells into a functional skeletal muscle tissue
The generation of functional skeletal muscle tissue from human pluripotent stem cells has not been reported. Here, the authors describe engineering of contractile skeletal muscle bundles in culture, which become vascularized and maintain functionality when transplanted into mice.
- Lingjun Rao
- , Ying Qian
- & Nenad Bursac
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Article
| Open AccessCardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues
Cardiomyocytes derived from human induced pluripotent stem cells could be used to generate cardiac tissues for regenerative purposes. Here the authors describe a method to obtain large bioengineered heart tissues showing advanced maturation, functional features and engraftment capacity.
- Ilya Y. Shadrin
- , Brian W. Allen
- & Nenad Bursac
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Article
| Open AccessMicrobial volatile communication in human organotypic lung models
There is a need for improved in vitro models of host-microbe interactions in the lung. Here, Barkal et al. present a microscale organotypic model of the human bronchiole for studying pulmonary infection, including volatile compound communication between microbial populations and host cells.
- Layla J. Barkal
- , Clare L. Procknow
- & David J. Beebe
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| Open AccessProgrammed biomolecule delivery to enable and direct cell migration for connective tissue repair
Dense connective tissues do not easily heal, in part due to a low supply of reparative cells. Here, the authors develop a fibrous scaffold for meniscal repair that sequentially releases collagenase and a growth factor at the injury site, breaking down the extracellular matrix and recruiting endogenous cells.
- Feini Qu
- , Julianne L. Holloway
- & Robert L. Mauck
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| Open AccessBioengineering of functional human induced pluripotent stem cell-derived intestinal grafts
There is a need for humanised grafts to treat patients with intestinal failure. Here, the authors generate intestinal grafts by recellularizing native intestinal matrix with human induced pluripotent stem cell-derived epithelium and human endothelium, and show nutrient absorption after transplantation in rats.
- Kentaro Kitano
- , Dana M. Schwartz
- & Harald C. Ott
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Article
| Open AccessMatrix degradability controls multicellularity of 3D cell migration
The fabrication of vascularized 3D tissues requires an understanding of how material properties govern endothelial cell invasion into the surrounding matrix. Here the authors integrate a non-swelling synthetic hydrogel with a microfluidic device to study chemokine gradient-driven angiogenic sprouting and find that matrix degradability modulates the collectivity of cell migration.
- Britta Trappmann
- , Brendon M. Baker
- & Christopher S. Chen
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| Open AccessBioengineered constructs combined with exercise enhance stem cell-mediated treatment of volumetric muscle loss
Volumetric muscle loss leads to functional muscle impairment, and current stem cell-based treatments show limited efficacy. Here, the authors generate a stem cell scaffold, implant it in mice, and show that an exercise regimen enhances innervation and restoration of muscle function in mice.
- Marco Quarta
- , Melinda Cromie
- & Thomas A. Rando
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| Open AccessEngineering the haemogenic niche mitigates endogenous inhibitory signals and controls pluripotent stem cell-derived blood emergence
The derivation of blood progenitor cells from human pluripotent stem cells is of interest for cell therapy but remains an inefficient process. Here the authors micropattern hPSC-derived haemogenic endothelial (HE) cells into spatially-organized, size-controlled colonies and identify a geometry that achieves increased efficiency in deriving blood cells.
- Nafees Rahman
- , Patrick M. Brauer
- & Peter W. Zandstra
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| Open AccessTissue engineering of acellular vascular grafts capable of somatic growth in young lambs
Current vessel grafts must be surgically replaced when the recipient outgrows them. Here, Syedain et al.bioengineer a tube of acellular matrix produced from sheep fibroblasts that is capable of cellularizaton and somatic growth when transplanted into growing lambs, eliminating the need for multiple graft surgeries.
- Zeeshan Syedain
- , Jay Reimer
- & Robert T. Tranquillo
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| Open AccessModelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids
Generating organized kidney tissues from human pluripotent stem cell is a major challenge. Here, Freedman et al. describe a differentiation system forming spheroids and tubular structures, characteristic of these kidney structures, and using CRISPR/Cas9, delete PKD1/2, to model polycystic kidney disease.
- Benjamin S. Freedman
- , Craig R. Brooks
- & Joseph V. Bonventre
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| Open AccessSelf-organizing human cardiac microchambers mediated by geometric confinement
Organogenesis is orchestrated by biochemical and biophysical stimuli. Here, Ma et al. generate a micro-patterned surface that provides mechanical cues which, when combined with biochemical signals, drive human pluripotent stem cells’ differentiation into beating cardiac microchambers resembling primitive hearts.
- Zhen Ma
- , Jason Wang
- & Kevin E. Healy
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| Open AccessArtificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue
Avoiding central cell necrosis at the centre of large engineered tissue constructs is an important issue forin vitrotissue engineering. Here, the authors demonstrate that this problem may be overcome by oxygenating human mesenchymal stem cells with artificial membrane-binding proteins.
- James P. K. Armstrong
- , Rameen Shakur
- & Anthony P. Hollander
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Reinforcement of hydrogels using three-dimensionally printed microfibres
Hydrogels are commonly used materials for tissue engineering, but they can lack the structural properties required for load-bearing and mechanical applications. Here, the authors prepare a polycaprolactone scaffold using melt-electrospinning to reinforce a gelatin methacrylamide hydrogel.
- Jetze Visser
- , Ferry P.W. Melchels
- & Jos Malda
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| Open AccessOn the tear resistance of skin
It is known that skin has a large tear resistance, but little is known of the mechanism behind this. Here, the authors carry out a structural analysis of rabbit skin to show how the deformation of collagen fibrils in the skin results in a strong resistance to tear propagation.
- Wen Yang
- , Vincent R. Sherman
- & Marc A. Meyers
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| Open AccessExperimental orthotopic transplantation of a tissue-engineered oesophagus in rats
Patients with oesophageal diseases may require surgical removal and replacement of the oesophagus. Here the authors seed mesenchymal stromal cells on a decellularized rat oesophagus and show that this bioengineered tissue construct restores swallowing function after transplantation into rats.
- Sebastian Sjöqvist
- , Philipp Jungebluth
- & Paolo Macchiarini
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Microgels on-demand
Traditional methods for forming hydrogel particles are limited by geometry and lack of addressability after synthesis. Here the authors use digital microfluidics to form individually addressable gels with customisable shapes and compositions.
- Irwin A. Eydelnant
- , Bingyu Betty Li
- & Aaron R. Wheeler
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Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells
The hair follicle bulge contains epithelial stem cells that contribute to follicle formation during each hair cycle. Here the authors differentiate human induced pluripotent stem cells into folliculogenic epithelial stem cells, which can produce all hair follicle lineages including a stem cell population.
- Ruifeng Yang
- , Ying Zheng
- & Xiaowei Xu
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Patterned prevascularised tissue constructs by assembly of polyelectrolyte hydrogel fibres
Tissue engineering relies on the vascular compatibility of the synthesised constructs with target tissues. Here, the authors fabricate a prevascularised tissue construct of cell-laden hydrogel fibres as a framework that allows the formation of vascularised adipose and hepatic tissues.
- Meng Fatt Leong
- , Jerry K. C. Toh
- & Jackie Y. Ying
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InVERT molding for scalable control of tissue microarchitecture
Artificially engineered tissues may be useful for regenerative therapies but their fabrication tends to be complicated. Stevens et al. present a technique for the precise organization of microstructurally complex tissues that works with a variety of cell types and does not require sophisticated equipment.
- K. R. Stevens
- , M. D. Ungrin
- & S. N. Bhatia
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| Open AccessIn vitro fabrication of functional three-dimensional tissues with perfusable blood vessels
Artificially engineered tissues may have many therapeutic applications but complex tissues are hard to create in vitro. Here, Okano and colleagues report the production of functional cardiac tissue sheets with perfusable blood vessels, which increase the thickness and survival of transplanted tissue.
- Hidekazu Sekine
- , Tatsuya Shimizu
- & Teruo Okano