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| Open AccessMechano-modulatory synthetic niches for liver organoid derivation
3D liver organoids hold great promise for regenerative medicine but the use of ill-defined matrices limits their potential. Here, the authors generate human and mouse liver organoids using a chemically defined matrix, and reveal a link between matrix stiffness and organoid growth that does not require acto-myosin contraction.
- Giovanni Sorrentino
- , Saba Rezakhani
- & Kristina Schoonjans
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Article
| Open AccessUncovering mutation-specific morphogenic phenotypes and paracrine-mediated vessel dysfunction in a biomimetic vascularized mammary duct platform
In vitro models of the human mammary gland have struggled to mimic the 3D morphogenic processes that occur in vivo. Here the authors develop a 3D microfluidic platform of a vascularized human mammary duct that simulates diverse morphogenic transitions and paracrine crosstalk.
- Matthew L. Kutys
- , William J. Polacheck
- & Christopher S. Chen
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Article
| Open AccessEndothelialization of arterial vascular grafts by circulating monocytes
Acellular tissue engineered vessels functionalised with VEGF are coated with a layer of endothelial cells after in vivo implantation, but the source of the cells are unknown. Here the authors provide evidence that monocytes expressing VEGF receptors can transdifferentiate into endothelial cells via a macrophage intermediate.
- Randall J. Smith Jr.
- , Bita Nasiri
- & Stelios T. Andreadis
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Article
| Open AccessFiber reinforced GelMA hydrogel to induce the regeneration of corneal stroma
Regeneration of corneal stroma has been a challenge due to its sophisticated structure and the easy transformation of the keratocyte. Here, the authors use a hydrogel reinforced with orthogonally aligned fibres and serum free medium to maintain keratocyte phenotype for the in vivo stromal regeneration.
- Bin Kong
- , Yun Chen
- & Shengli Mi
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Article
| Open AccessNeural cell integration into 3D bioprinted skeletal muscle constructs accelerates restoration of muscle function
3D bioprinting of skeletal muscle using primary human muscle progenitor cells results in correct muscle architecture, but functional restoration in rodent models is limited. Here the authors include human neural stem cells into bioprinted skeletal muscle and observe improved architecture and function in vivo.
- Ji Hyun Kim
- , Ickhee Kim
- & Sang Jin Lee
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Article
| Open AccessIntegrin-specific hydrogels modulate transplanted human bone marrow-derived mesenchymal stem cell survival, engraftment, and reparative activities
Mesenchymal stromal cells enhance bone and cartilage repair, but are limited by poor survival and retention after transplantation. Here, the authors show that synthetic hydrogels presenting integrin-specific peptides enhance the survival and persistence of human mesenchymal stromal cells after transplant, as well as bone repair.
- Amy Y. Clark
- , Karen E. Martin
- & Andrés J. García
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Article
| Open AccessGenerating ring-shaped engineered heart tissues from ventricular and atrial human pluripotent stem cell-derived cardiomyocytes
The cellular composition of previous engineered heart tissue is often heterogeneous. Here, the authors create chamber-specific human pluripotent stem cell-derived cardiomyocytes to form both ventricular and atrial cells before embedding in collagen-based matrix to form ring-shaped engineered heart tissue.
- Idit Goldfracht
- , Stephanie Protze
- & Lior Gepstein
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Article
| Open AccessIn vivo engineered extracellular matrix scaffolds with instructive niches for oriented tissue regeneration
Extracellular matrix (ECM) is an ideal scaffold for tissue engineering but tends to lack hierarchical structure. Here the authors implant sacrificial templates subcutaneously to build an organised ECM scaffold, and following template removal and decellularisation use these scaffolds to create functionally integrated muscle, nerve and artery in vivo.
- Meifeng Zhu
- , Wen Li
- & Deling Kong
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Article
| Open AccessEngineering transferrable microvascular meshes for subcutaneous islet transplantation
The success of engineered tissue depends on the integration of a dense vascular network to supply nutrients and remove waste products. Here the authors design high density microvascular meshes made through an anchored self-assembly mechanism, and use these meshes to support subcutaneous pancreatic islet survival in a mouse diabetes model.
- Wei Song
- , Alan Chiu
- & Minglin Ma
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Article
| Open Access3D extracellular matrix microenvironment in bioengineered tissue models of primary pediatric and adult brain tumors
The brain extracellular matrix (ECM) is altered in brain tumors, but its role in cancer progression and drug sensitivity are difficult to study. Here the authors develop a 3D bioengineered brain tissue model using patient-derived samples and tunable brain-derived ECM to examine the interplay between cells and the ECM.
- Disha Sood
- , Min Tang-Schomer
- & David L. Kaplan
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Article
| Open AccessInsulin-producing organoids engineered from islet and amniotic epithelial cells to treat diabetes
Islet transplantation is a feasible approach to treat type I diabetes, however inflammation and poor vascularisation impair long-term engraftment. Here the authors show that incorporating human amniotic epithelial cells into islet organoids improves engraftment and function of organoids, through enhanced revascularisation.
- Fanny Lebreton
- , Vanessa Lavallard
- & Ekaterine Berishvili
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Article
| Open AccessSpatiotemporal material functionalization via competitive supramolecular complexation of avidin and biotin analogs
Controlled patterning of functionality within hydrogels typically involves complex chemistry. Here, the authors report on a simple competitive binding strategy using avidin and biotin analogs in an injectable biomaterial for spatiotemporally controlled presentation of biochemical stimuli to cells.
- Tom Kamperman
- , Michelle Koerselman
- & Jeroen Leijten
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Article
| Open AccessMicroporous methacrylated glycol chitosan-montmorillonite nanocomposite hydrogel for bone tissue engineering
Injectable hydrogels could be used to repair bone defects. Here the authors incorporate nanoclay particles into chitosan creating an interconnected microporous hydrogel and show that this hydrogel can support MSC proliferation and differentiation in vitro, and support the recruitment of native cells and bone regeneration in a mouse calvarial defect model.
- Zhong-Kai Cui
- , Soyon Kim
- & Min Lee
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Article
| Open AccessRapid fabrication of vascularized and innervated cell-laden bone models with biomimetic intrafibrillar collagen mineralization
Bone tissue is a complex organic-inorganic nanocomposite and strategies that replicate the characteristics of bone tissue are scarce. Here the authors demonstrate the deposition of nanoscale apatite in collagen embedded with mesenchymal, vascular and nerve cells, using a protein-guided biomineralization approach.
- Greeshma Thrivikraman
- , Avathamsa Athirasala
- & Luiz E. Bertassoni
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Article
| Open AccessRapid fabrication of reinforced and cell-laden vascular grafts structurally inspired by human coronary arteries
Bioengineering of small diameter vascular grafts that recapitulate the features of native vessels is extremely challenging. Here the authors present a combined dip-spinning and blow-spinning technology to fabricate multi-layered cell-embedded grafts with native mechanical properties.
- Tamara L. Akentjew
- , Claudia Terraza
- & Juan Pablo Acevedo
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Article
| Open AccessDevelopment of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes
The development of tissue-engineered vascular grafts heavily relies on the availability of large animal models that allow long-term assessment of graft patency. Here Itoh et al. propose a novel model of immunodeficient pigs that allows long-term accommodation of human cell-derived three-dimensional bioprinted vascular tubes.
- Manabu Itoh
- , Yosuke Mukae
- & Eiji Kobayashi
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Article
| Open AccessMicroclot array elastometry for integrated measurement of thrombus formation and clot biomechanics under fluid shear
Blood clotting is a complex process involving platelet adhesion and clot stiffening. Here the authors present a microfluidic system to recapitulate the dynamic changes in clot mechanics under physiological shear.
- Zhaowei Chen
- , Jiankai Lu
- & Ruogang Zhao
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Article
| Open AccessEnzyme-responsive progelator cyclic peptides for minimally invasive delivery to the heart post-myocardial infarction
Injectable hydrogels have gained significant interest; yet, due to high viscosity, many are unsuitable for catheter delivery. Here, the authors report on cyclic peptides with low viscosity for catheter delivery, which form self-assembled peptide hydrogels following enzymatic cleavage and demonstrated delivery in vivo.
- Andrea S. Carlini
- , Roberto Gaetani
- & Nathan C. Gianneschi
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| Open AccessHigh-resolution acoustophoretic 3D cell patterning to construct functional collateral cylindroids for ischemia therapy
Engineering 3D tissues faces the challenge of adequate vascularisation for nutrient delivery and gas exchange deep inside the construct. Here the authors use surface acoustic waves to create an aligned array of blood vessels in a hyaluronic acid hydrogel and use it to improve function in a mouse hindlimb ischemia model.
- Byungjun Kang
- , Jisoo Shin
- & Hyungsuk Lee
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| Open AccessA biomaterial with a channel-like pore architecture induces endochondral healing of bone defects
A bioengineering approach to enhance the regeneration of large bone defects is lacking. Here, the authors show that a biomaterial scaffold with a channel-like pore architecture enables organized endochondral ossification through directional cell recruitment and extracellular matrix alignment.
- A. Petersen
- , A. Princ
- & G. N. Duda
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| Open AccessMulti-stage bioengineering of a layered oesophagus with in vitro expanded muscle and epithelial adult progenitors
Combining decellularised scaffolds with patient-derived cells holds promise for bioengineering of functional tissues. Here the authors develop a two-stage approach to engineer an oesophageal graft that retains the structural organisation of native oesophagus.
- Luca Urbani
- , Carlotta Camilli
- & Paolo De Coppi
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Article
| Open AccessInjectable antibacterial conductive nanocomposite cryogels with rapid shape recovery for noncompressible hemorrhage and wound healing
To improve trauma survival and surgical outcomes, hemostatic agents are needed. Here, the authors report on the development of injectable, biocompatible carbon nanotube reinforced quaternized chitosan cryogels with shape memory, conductivity and antibacterial properties for hemostatic control.
- Xin Zhao
- , Baolin Guo
- & Peter X. Ma
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Article
| Open AccessFibrotic microtissue array to predict anti-fibrosis drug efficacy
A bottleneck in developing new anti-fibrosis therapies is the absence of suitable in vitro models that recapitulate key features of fibrogenesis. Here the authors develop a tissue-on-a-chip model of lung fibrosis and test the therapeutic efficacy of two recent FDA-approved drugs.
- Mohammadnabi Asmani
- , Sanjana Velumani
- & Ruogang Zhao
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| Open AccessPrecisely printable and biocompatible silk fibroin bioink for digital light processing 3D printing
Although 3D bioprinting technology has gained much attention in the field of tissue engineering, there are still several significant challenges that need to be overcome. Here, the authors present silk fibroin bioink with printability and biocompatibility suited for digital light processing 3D printing.
- Soon Hee Kim
- , Yeung Kyu Yeon
- & Chan Hum Park
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Article
| Open AccessSurface tension-assisted additive manufacturing
Integrating cell-laden hydrogels effectively into the 3D printing process is a challenge in the creation of tissue engineering scaffolds. Here, the authors describe an additive manufacturing technique to combine polymer and cell-containing networks with 3D-printed mechanical supports.
- Héloïse Ragelle
- , Mark W. Tibbitt
- & Robert Langer
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Article
| 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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Article
| 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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| 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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Article
| 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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Article
| 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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Article
| 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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Article
| 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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Article
| 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