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Article
| Open AccessEmergent collective organization of bone cells in complex curvature fields
It remains unclear how cells respond to complex extracellular geometries at the mesoscale. Here, the authors study the organization of bone cells in landscapes with varying curvatures, observing a preference for local concavities, multicellular bridging, and collective stress fiber orientation.
- Sebastien J. P. Callens
- , Daniel Fan
- & Amir A. Zadpoor
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Article
| Open AccessBioengineered liver crosslinked with nano-graphene oxide enables efficient liver regeneration via MMP suppression and immunomodulation
Bioengineered livers using decellularized scaffolds have been considered as an alternative to donor organs. Here, the authors modulate biophysical properties of decellularized scaffolds by crosslinking with nano-graphene oxide, thereby greatly enhancing therapeutic efficacy of bioengineered livers.
- Da-Hyun Kim
- , Min-Ji Kim
- & Kyung-Sun Kang
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Article
| Open AccessLight-driven biological actuators to probe the rheology of 3D microtissues
The mechanical properties of biological tissues are key to their integrity and function. Here, the authors engineer 3D microtissues from optogenetically modified fibroblasts and use light to quantify tissue elasticity and strain propagation using their own constituent cells as internal actuators.
- Adrien Méry
- , Artur Ruppel
- & Thomas Boudou
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Article
| Open AccessVolumetric additive manufacturing of pristine silk-based (bio)inks
Volumetric additive manufacturing of protein scaffolds has a wide range of possible biomedical applications. Here the authors report on the bioprinting of unmodified silk sericin and silk fibroin inks with shape-memory and tuneable mechanical properties and demonstrate the potential of the inks in different applications.
- Maobin Xie
- , Liming Lian
- & Yu Shrike Zhang
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Article
| Open AccessImplantable niche with local immunosuppression for islet allotransplantation achieves type 1 diabetes reversal in rats
Islet transplantation for type 1 diabetes management is hindered by the life-long need for immunosuppressive medications. Here, the authors report an islet encapsulation device with local anti-rejection drug release that achieves long-term diabetes reversal in male rats and reduces drug-related toxicity.
- Jesus Paez-Mayorga
- , Jocelyn Nikita Campa-Carranza
- & Alessandro Grattoni
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Article
| Open AccessBead-jet printing enabled sparse mesenchymal stem cell patterning augments skeletal muscle and hair follicle regeneration
Current mesenchymal stem cell (MSC) transplantation practices are limited by the loss or reduced performance of MSCs. Here the authors develop a bead-jet printer for intraoperative formulation and printing of MSCs-laden Matrigel beads to improve skeletal muscle and hair follicle regeneration.
- Yuanxiong Cao
- , Jiayi Tan
- & Shaohua Ma
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Article
| Open AccessEndowing universal CAR T-cell with immune-evasive properties using TALEN-gene editing
Host versus graft reaction is a major impediment to CAR-T cell immune therapy in allogeneic settings. Authors show here that CAR-T cells, engineered to be deficient in MHC I expression but to express the NK inhibitor HLA-E, are resistant to destruction by both T and NK cells of the host.
- Sumin Jo
- , Shipra Das
- & Julien Valton
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Article
| Open AccessMolecularly cleavable bioinks facilitate high-performance digital light processing-based bioprinting of functional volumetric soft tissues
Soft tissue fabrication using digital light processing remains challenging. Here the authors present a molecular cleavage approach to achieve high-performance bioprinting of constructs with tissue-matching mechanical properties and structural complexity.
- Mian Wang
- , Wanlu Li
- & Yu Shrike Zhang
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Article
| Open AccessAn instantly fixable and self-adaptive scaffold for skull regeneration by autologous stem cell recruitment and angiogenesis
Limited stem cells and mismatched interface fusion have plagued biomaterial-mediated cranial reconstruction. Here, the authors engineer an instantly fixable and self-adaptive scaffold to promote calcium chelation and interface integration, regulate macrophage M2 polarization, and recruit endogenous stem cells.
- Gonggong Lu
- , Yang Xu
- & Xingdong Zhang
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Article
| Open AccessHigh-throughput production of functional prototissues capable of producing NO for vasodilation
Protoissues have received a lot of attention for studying cell interaction and for biomedical engineering. Here, the authors demonstrate a high-throughput, bottom-up approach to assemble spatial programmable prototissues based on the magnetic Archimedes affect and demonstrate biomedical application for producing NO for vasodilation.
- Xiangxiang Zhang
- , Chao Li
- & Xiaojun Han
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Article
| Open AccessMechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip
Mechanical forces in lungs facilitate breathing motions. Here the authors use a microfluidic human lung alveolus chip to study influenza infection and find that mechanical forces from active chips also induce innate inflammatory responses via, at least partially, signaling from TRPV4 and RAGE, thereby implicating them as potential therapeutic targets for lung inflammation.
- Haiqing Bai
- , Longlong Si
- & Donald E. Ingber
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Article
| Open AccessTissue extracellular matrix hydrogels as alternatives to Matrigel for culturing gastrointestinal organoids
The culture of gastrointestinal organoids relies on Matrigel that has several drawbacks for clinical application. Here, the authors report the feasibility of gastrointestinal tissue-mimetic matrices as effective alternatives to Matrigel for organoid culture and transplantation.
- Suran Kim
- , Sungjin Min
- & Seung-Woo Cho
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Article
| Open AccessUsing CRISPR-Kill for organ specific cell elimination by cleavage of tandem repeats
How double strand breaks (DSBs) are repaired within the plant 45S rDNA repeats is unclear. Here, the authors show that Cas9-mediated DSBs in 45S rDNA are mainly repaired by cNHEJ and describe CRISPR-Kill as a tool for organ-specific cell elimination by targeting functional repetitive DNA in Arabidopsis.
- Angelina Schindele
- , Fabienne Gehrke
- & Holger Puchta
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Article
| Open AccessQuantitative 3D imaging of the cranial microvascular environment at single-cell resolution
Vascularization is critical for cranial bone growth, maintenance, and healing, but it remains unknown how blood vessels are spatially distributed in the calvarium, and how they interact with skeletal progenitors during these processes. Here, the authors apply a quantitative light-sheet imaging platform to visualize and analyze the relationship between blood vessels and skeletal progenitors throughout the murine calvarium.
- Alexandra N. Rindone
- , Xiaonan Liu
- & Warren L. Grayson
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Article
| Open AccessEngineered whole cut meat-like tissue by the assembly of cell fibers using tendon-gel integrated bioprinting
Mammalian cell-based cultured meat has mostly been unstructured, leaving a demand for artificial steak-like meat. Here the authors present an assembled steak-like tissue of bovine skeletal muscle, adipose tissue, and blood capillary tissue fabricated by tendon-gel integrated printing technology.
- Dong-Hee Kang
- , Fiona Louis
- & Michiya Matsusaki
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Article
| Open AccessMicrochannelled alkylated chitosan sponge to treat noncompressible hemorrhages and facilitate wound healing
Developing effective treatments for noncompressible hemorrhages remains a challenge. Here the authors engineer alkylated chitosan sponges with highly interconnective microchannels and demonstrate anti-infective activity, as well as higher pro-coagulant, hemostatic and wound healing capacities compared to clinically-used materials in rat and pig liver models.
- Xinchen Du
- , Le Wu
- & Meifeng Zhu
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Article
| Open AccessMicrofluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids
Brain organoids derived from human pluripotent stem cells can model human brain development and disease, though current culture systems fail to ensure reliable production of high-quality organoids. Here the authors combine human brain extracellular matrix and culture in a microfluidic device to promote structural and functional maturation of human brain organoids.
- Ann-Na Cho
- , Yoonhee Jin
- & Seung-Woo Cho
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Article
| Open Access4D polycarbonates via stereolithography as scaffolds for soft tissue repair
Shape memory scaffolds are needed for minimally invasive tissue repair and void filling. Here the authors report on the development of 4D printed polycarbonate-based scaffolds with surface degradation properties which fill voids without deforming tissue and allow for tissue ingrowth with reduced immune response.
- Andrew C. Weems
- , Maria C. Arno
- & Andrew P. Dove
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Article
| Open AccessVapor-phased fabrication and modulation of cell-laden scaffolding materials
Current methods for the modular assembly of biomaterials are associated with limitations. Here the authors implement vapor-phase deposition to fabricate 3D polymeric materials that permit biomolecule functionalization, tunable mass transport and mechanical properties, as well as control over boundaries between compartments, and analyze the behavior of 3D encapsulated cells.
- Chih-Yu Wu
- , Ting-Ying Wu
- & Hsien-Yeh Chen
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Article
| Open AccessMicrofluidic platform accelerates tissue processing into single cells for molecular analysis and primary culture models
Existing methods for tissue dissociation are inefficient and lead to variable outcomes and biases. Here, the authors present a microfluidic platform that combines digestion, disaggregation and filtration of tissue to allow single cell analysis and RNA sequencing.
- Jeremy A. Lombardo
- , Marzieh Aliaghaei
- & Jered B. Haun
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Article
| Open AccessJanus 3D printed dynamic scaffolds for nanovibration-driven bone regeneration
Fabrication of dynamic, reversible and biocompatible scaffolds with non-invasive external triggers has so far been limited. Here, the authors report on the creation of 3D printed scaffolds with Janus structure that produce nanovibrations when exposed to ultrasound, promoting bone regeneration.
- Sandra Camarero-Espinosa
- & Lorenzo Moroni
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Article
| Open AccessConcomitant control of mechanical properties and degradation in resorbable elastomer-like materials using stereochemistry and stoichiometry for soft tissue engineering
The creation of biomaterials which are resorbable and have biomimetic mechanical properties is key to successful tissue engineering. Here the authors report on the creation of a new biopolymer where the mechanical properties can be tuned by changing the ratios of cis:trans double bonds in the backbone.
- Mary Beth Wandel
- , Craig A. Bell
- & Matthew L. Becker
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Review Article
| Open AccessPlant-based and cell-based approaches to meat production
Large-scale meat production can have negative impacts on public health, the environment and animal welfare. In this Review, the authors consider plant-based and cell-based approaches to meat production and the challenges they face.
- Natalie R. Rubio
- , Ning Xiang
- & David L. Kaplan
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Article
| Open AccessModeling early stage atherosclerosis in a primary human vascular microphysiological system
Human microphysiological systems (MPS) have some advantages over animal models to study the mechanisms of disease. Here the authors use a tissue-engineered blood vessel MPS to create a model of early stage atherosclerosis and assess the effect of several drugs.
- Xu Zhang
- , Muath Bishawi
- & George A. Truskey
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Article
| Open AccessDevelopmental GABA polarity switch and neuronal plasticity in Bioengineered Neuronal Organoids
Brain organoids are important tools to study early development and disease but little is known of their network activity and plasticity. Here the authors generate iPSC-derived neuronal organoids that display early network formation and maturation with evidence for a GABA polarity switch and long-term potentiation.
- Maria-Patapia Zafeiriou
- , Guobin Bao
- & Wolfram-Hubertus Zimmermann
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Article
| 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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Article
| 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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Article
| 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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Article
| 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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Article
| 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