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| 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 AccessA predictive computational platform for optimizing the design of bioartificial pancreas devices
Transplanting encapsulated insulin-producing cells may achieve a functional cure for type 1 diabetes, but efficacy is constrained by mass transfer limits. Here, the authors report a dynamic computational platform to investigate the therapeutic potency of such programmable bioartificial pancreas devices.
- Alexander U. Ernst
- , Long-Hai Wang
- & Minglin Ma
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Article
| Open AccessGenetically stable CRISPR-based kill switches for engineered microbes
Biocontainment is a key to developing safe genetically-engineered microbes (GEMs). Here the authors demonstrate genetically stable CRISPR-based kill switches that control GEMs’ viability in animal hosts, enabling their safe biomedical applications.
- Austin G. Rottinghaus
- , Aura Ferreiro
- & Tae Seok Moon
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Article
| Open AccessA bioinspired scaffold for rapid oxygenation of cell encapsulation systems
Cell encapsulation into biomaterials for transplantation is currently limited by inadequate oxygenation. Here the authors present a biomimetic scaffold featuring internal continuous air channels endowed with 10,000-fold higher O2 diffusivity than hydrogels and demonstrate correction of diabetes in immunocompetent mice using rat islets for over 6 months.
- Long-Hai Wang
- , Alexander Ulrich Ernst
- & Minglin Ma
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Article
| Open AccessEfficient intracellular delivery of proteins by a multifunctional chimaeric peptide in vitro and in vivo
Protein delivery with cell-penetrating peptides suffers from ineffective endosomal escape and low tolerance in serum, thereby limiting treatment success. Here the authors present an intracellular protein delivery system and demonstrate efficient delivery in vitro and therapeutic efficacy in a liver failure model in vivo.
- Siyuan Yu
- , Han Yang
- & Ningshao Xia
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Article
| Open AccessEnhancing myocardial repair with CardioClusters
Despite recent progress to advance cardiac cell-based therapy for patients, heart failure mortality rivals most cancers. Here, the authors describe an approach to control and pattern 3 distinct human cardiac cell populations to promote superior repair and regeneration after myocardial infarction.
- Megan M. Monsanto
- , Bingyan J. Wang
- & Mark A. Sussman
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Article
| Open AccessLITESEC-T3SS - Light-controlled protein delivery into eukaryotic cells with high spatial and temporal resolution
The type III secretion system (T3SS) of bacteria can be used to inject cargo into eukaryotic cells but its lack of target specificity is a disadvantage. Here the authors place the T3SS under the regulation of light by engineering optogenetic switches into the dynamic cytosolic T3SS component SctQ.
- Florian Lindner
- , Bailey Milne-Davies
- & Andreas Diepold
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Article
| Open AccessBiointerfacial self-assembly generates lipid membrane coated bacteria for enhanced oral delivery and treatment
Oral microbiota delivery is an approach to treat and prevent disease but suffers from low retention and bioavailability. Here the authors report on a lipid coating to protect against environmental assault maintaining viability and bioactivity of the bacteria and demonstrate effective application in a colitis model.
- Zhenping Cao
- , Xinyue Wang
- & Jinyao Liu
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Article
| Open AccessAn anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles
Most reagents designed to deliver cargo into cells are cationic and so cannot deliver cationic cargo. Here the authors show that pretreating cells with the anionic polymer poly(propylacrylic acid) facilitates the uptake and endosomal escape of a wide variety of cationic cargo in numerous cell types.
- Brian C. Evans
- , R. Brock Fletcher
- & Craig L. Duvall
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Article
| Open AccessCellular internalization of bystander nanomaterial induced by TAT-nanoparticles and regulated by extracellular cysteine
To enter the cells, nanomaterials often need covalent conjugation with cell-penetrating ligands such as TAT. Here, the authors show that simple mixing with TAT-coupled nanoparticles enables the cellular uptake of unfunctionalized nanoparticles, and its activity is stimulated by cysteine in the medium.
- Yushuang Wei
- , Tang Tang
- & Hong-Bo Pang
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Article
| Open AccessCamouflaging bacteria by wrapping with cell membranes
The use of engineered bacteria for biomedical applications is limited by side effects such as inflammatory response. Here the authors engineer cell membrane coated bacteria as in vivo tumor imaging agents, and show that these generate a lower inflammatory response and reduced macrophage clearance.
- Zhenping Cao
- , Shanshan Cheng
- & Jinyao Liu
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Article
| Open AccessArtificial cell membrane binding thrombin constructs drive in situ fibrin hydrogel formation
The incorporation of cells into tissue engineering scaffolds can be a major challenge. Here, the authors report on anchoring thrombin to cell membranes for the in situ formation of fibrin scaffolds around the modified cells, demonstrate scaffold formation in vitro and show cell survival in vivo.
- Robert C. Deller
- , Thomas Richardson
- & Adam W. Perriman
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Article
| Open AccessSynthetic molecular evolution of hybrid cell penetrating peptides
Therapeutic peptide nucleic acids can be delivered into cells by conjugation to cell penetrating peptides (CPPs), but efficiency is usually low. Here the authors use synthetic molecular evolution and a luciferase-based library screen to generate new CPPs with improved efficiency and lower toxicity.
- W. Berkeley Kauffman
- , Shantanu Guha
- & William C. Wimley
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Article
| Open AccessSingle quantum dot tracking reveals the impact of nanoparticle surface on intracellular state
Quantum dots (QDs) mimic delivery agents for drugs and analytic compounds, but which route do they take inside cells? Here, the authors developed a technique to follow QDs, and they show that zwitterionic nanoparticle surface coatings make for the best delivery vehicle.
- Mohammad U. Zahid
- , Liang Ma
- & Andrew M. Smith
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Article
| Open AccessIn vivo transplantation of 3D encapsulated ovarian constructs in rats corrects abnormalities of ovarian failure
Cell-based hormone replacement therapy (cHRT) may be an alternative therapy to pharmacological (p)HRT. Here, the authors show that implanted 3D bioengineered ovarian constructs of granulosa and theca cells in ovariectomized rats recapitulate native cell interactions and improve efficacy compared to similar doses of pHRT.
- Sivanandane Sittadjody
- , Justin M. Saul
- & Emmanuel C. Opara