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| Open AccessA mechanical-assisted post-bioprinting strategy for challenging bone defects repair
Bioprinting has revitalized tissue regeneration efforts, yet challenges persist due to cell damage during fabrication and mechanical instability of printed scaffolds. Here, the authors develop a mechanical-assisted post-bioprinting strategy for loading cells into hollow scaffolds that effectively repair challenging bone defects.
- Jirong Yang
- , Zhigang Chen
- & Changshun Ruan
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Article
| Open AccessProinflammatory polarization of engineered heat-inducible macrophages reprogram the tumor immune microenvironment during cancer immunotherapy
Alternatively activated macrophages have a pivotal role in resolving inflammation but in the tumour microenvironment they are immunosuppressive. Here author show that adoptively transferred engineered macrophages harbouring a heat-inducible genetic switch can resist the polarizing effect of the tumour microenvironment, and do not only remain pro-inflammatory themselves but also re-polarise the endogenous macrophages upon controlled warming with a purpose-made device.
- Yanan Xue
- , Xiaojie Yan
- & Yuan Ping
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Article
| Open AccessTargeted therapies of inflammatory diseases with intracellularly gelated macrophages in mice and rats
Membrane-decorated nanomedicines often suffer from reduced efficacy caused by membrane artefacts during the coating process. Here the authors show that intracellularly gelated macrophages preserve membrane properties, stay stable under ambient temperature, and show therapeutic effects in murine models of joint and lung inflammation.
- Cheng Gao
- , Qingfu Wang
- & Ruibing Wang
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Article
| Open AccessAdoptive macrophage directed photodynamic therapy of multidrug-resistant bacterial infection
There is increased demand for effective, broad-spectrum treatment options against severe, multi-drug resistant bacterial infections. Here, Wang et al describe an effective photodynamic therapy based on the adoptive transfer of macrophages loaded with a lysosomal photosensitiser.
- Zehui Wang
- , Anhua Wu
- & Yi Xiao
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Article
| Open AccessElectrocatalytic on-site oxygenation for transplanted cell-based-therapies
Oxygen is the most limiting factor in cell transplantation. Here, the authors present an on-site oxygen production platform for implantable cell therapeutics via electrocatalytic water electrolysis, demonstrating the maintenance of high cell loading in hypoxic incubation and a rat model.
- Inkyu Lee
- , Abhijith Surendran
- & Tzahi Cohen-Karni
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Article
| Open AccessNongenetic surface engineering of mesenchymal stromal cells with polyvalent antibodies to enhance targeting efficiency
Limited delivery of therapeutic cells to diseased tissue hampers the effective application of mesenchymal stromal cells (MSCs). Here, authors modify the cell surface with polyvalent antibodies using DNA-templated assembly, and show that polyvalent interactions can be used to improve the targeting efficiency of MSCs.
- Tenghui Ye
- , Xi Liu
- & Peng Shi
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Article
| Open AccessMetabolic Reprogramming via ACOD1 depletion enhances function of human induced pluripotent stem cell-derived CAR-macrophages in solid tumors
The functional-metabolic state of macrophages fundamentally influences the tumour microenvironment, making adoptive cell therapy with pro-inflammatory macrophages an attractive anti-tumour approach. Here authors introduce pluripotent stem cell-derived CAR-macrophage that are depleted of ACOD1, an essential gene in itaconate metabolism, which reprograms them to a pro-inflammatory state enabling enhanced anti-tumour function.
- Xudong Wang
- , Siyu Su
- & Jin Zhang
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Article
| Open AccessEfficient intervention for pulmonary fibrosis via mitochondrial transfer promoted by mitochondrial biogenesis
Using healthy mitochondria to restore impaired mitochondrial homeostasis is a promising therapy for pulmonary fibrosis. Here the authors use joint-engineered mesenchymal stem cells for efficient mitochondrial delivery to injured lung cells, showing a successful mitigation of the disease.
- Ting Huang
- , Ruyi Lin
- & Jianqing Gao
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Article
| Open AccessCell type-specific delivery by modular envelope design
Targetable delivery vectors for genetic cargo are needed. Here the authors report a modular platform with separate fusion and targeting components—Delivery to Intended REcipient Cells Through Envelope Design (DIRECTED)—and show cell type-specific delivery.
- Daniel Strebinger
- , Chris J. Frangieh
- & Feng Zhang
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Article
| Open AccessMetabolic glycan labeling immobilizes dendritic cell membrane and enhances antitumor efficacy of dendritic cell vaccine
Dendritic cell (DC) vaccines were among the first FDA-approved cancer immunotherapies but have been limited by the modest therapeutic efficacy. Here, authors report a facile metabolic glycan labeling approach to improving the cytotoxic T lymphocyte response and antitumor efficacy of DC vaccines.
- Joonsu Han
- , Rimsha Bhatta
- & Hua Wang
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Article
| Open AccessAntigen-dependent IL-12 signaling in CAR T cells promotes regional to systemic disease targeting
Targeting solid tumours by chimeric antigen receptor (CAR) T cells require strategies that improve trafficking and effector function of these cells in the immunologically hostile cancer microenvironment. Here, authors show that CAR T cells engineered with incorporation of the CD28 transmembrane domain to the 4-1BB costimulatory domain and a membrane-bound form of IL-12 can achieve efficient anti-tumour activity and promote systemic disease targeting via regional T cell delivery in multi-metastatic disease models.
- Eric Hee Jun Lee
- , John P. Murad
- & Saul J. Priceman
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Article
| Open AccessTransplanting FVIII/ET3-secreting cells in fetal sheep increases FVIII levels long-term without inducing immunity or toxicity
The authors show in a preclinical large animal model that in utero delivery of FVIII-secreting human placental cells is feasible, safe, and yields elevated plasma FVIII activity for at least three years without triggering immunity, affirming prenatal treatment of hemophilia A.
- Martin Rodriguez
- , Brady Trevisan
- & Graça Almeida-Porada
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Article
| Open AccessTargeted cross-linker delivery for the in situ mapping of protein conformations and interactions in mitochondria
Current methods for analysing protein structures and interactions generally require the separation of specific organelles or changes to the intracellular environment. Here, authors developed nanocarrier-based cross-linking mass spectrometry techniques to assess mitochondrial proteins within living cells.
- Yuwan Chen
- , Wen Zhou
- & Yukui Zhang
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Article
| Open AccessIn-vivo programmable acoustic manipulation of genetically engineered bacteria
In vivo manipulation of cells has applications in cell-based therapy, tissue engineering and targeted drug delivery. Here the authors demonstrate in vivo programmable acoustic manipulation of genetically engineered bacteria using holographic acoustic tweezers.
- Ye Yang
- , Yaozhang Yang
- & Hairong Zheng
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Article
| Open AccessDesign of bacteriophage T4-based artificial viral vectors for human genome remodeling
Safe delivery of genes is needed for gene therapy. Here the authors build “artificial viral vectors” (AVVs) by engineering the well-characterised structural components of bacteriophage T4: the large capacity, all-in-one, multiplex, programmable, and phage-based AVV nanomaterials have potential for gene therapy.
- Jingen Zhu
- , Himanshu Batra
- & Venigalla B. Rao
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Perspective
| Open AccessMedical microrobots in reproductive medicine from the bench to the clinic
Microrobotics is an emerging technology with wide implications for medical fields, such as assisted reproduction. Here the authors show how the key challenges regarding materials, processes and engineering as well as ethical and regulatory implications can be addressed towards a clinical adoption.
- Richard Nauber
- , Sandhya R. Goudu
- & Mariana Medina-Sánchez
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Article
| Open AccessHydrogel oxygen reservoirs increase functional integration of neural stem cell grafts by meeting metabolic demands
Injectable biomimetic hydrogels hold significant promise for tissue engineering applications. Here, the authors present a hybrid myoglobin:peptide hydrogel to overcome a critical oxygen shortage following neural stem cell transplantation, thus increasing cell survival and integration.
- Y. Wang
- , E. R. Zoneff
- & D. R. Nisbet
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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 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