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Bioprinting and synthetic biology approaches to engineer functional endocrine pancreatic constructs.

Diabetes is a complex disease affecting over 500 million people worldwide. Traditional approaches, such as insulin delivery, are mainstay tr … development of this field, with a particular focus on the convergence of synthetic biology and cell engineering with bioprinting, which opens new avenues for developing advanced in vitro models and regenerative, transplantable grafts, with the potential to provide independence from exogenous insulin administration.

Site-directed tyrosinase conjugation on engineered ferritin retains immune recognition.

Ferritin (Ft) nanoparticles are promising scaffolds for antigen display in vaccine design due to their stability, defined architecture, and biocompatibility. Enzymatic methods, such as tyrosinase catalysis, enable covalent antigen conjugation by oxidizing tyrosine residues into o-quinones that react with accessible cysteine thiols. Here, we engineered Pyrococcus furiosus ferritin (PfFt) by introducing single cysteines at defined positions (K8C, D33C, and E92C) to enable site-specific bioconjugation. All PfFt variants retained their quaternary nanoparticle structure, as confirmed by mass spectr

Tissue-engineered tubular substitutions for urinary diversion in a preclinical rabbit model.

OBJECTIVE: To develop and evaluate tissue-engineered tubular constructs using homologous adipose-derived stem cells (ASCs), smooth muscle cells (SMCs), and decellularized fish swim bladder (DFSB) matrix for urinary diversion in a rabbit model. METHODS: Rabbit ASCs and SMCs were isolated and expanded in vitro; cultured cells were seeded onto bilateral surfaces of DFSB scaffolds followed by 7-day incubation; cell-seeded matrices were shaped into tubular constructs; constructs underwent 2-week in vivo pre-vascularization within omental pouches. Experimental group rabbits (n=24) underwent complet

Стратегия проектирования, основанная на модели, для разработки систем обнаружения, регулируемых МОКРНА.

МИРНК являются перспективными диагностическими биомаркерами. Эти небольшие молекулы РНК всегда присутствуют в организме человека, но становятся дисрегулируемыми, когда человек развивает определенные болезни. Хотя обнаружение этих биомаркеров в ходе испытаний без ячеек является постоянной работой, нынешние системы часто концентрируются исключительно на обнаружении наличия или отсутствия конкретной miRNA, а не концентрации miRNA. Таким образом, при проведении этих тестов могут не учитываться относительные изменения концентрации miRNA в случае дизакции, вызванной болезнями. Эта работа, осуществля

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miRNAs are promising diagnostic biomarkers. These small RNA molecules are always present in the human body but become dysregulated when a pe … healthy (no output signal) or indicative of disease (strong output signal). To aid the experimental engineering of the test, here we use mathematical models to evaluate and assess different candidate networks. We apply a previously published multi-objective optimisation strategy to obtain designs that satisfy relevant constraints, such as low basal expression …

Engineered extracellular vesicles as "supply vehicles" to alleviate type 1 diabetes.

Recent findings have indicated that the deficiency of inhibitory programmed cell death ligand 1 (PD-L1) and galectin-9 (Gal-9) in pancreatic β-cells is associated with the progression of type 1 diabetes (T1D). This suggests that exogenous PD-L1 and Gal-9 may have promising potential as therapeutics for the treatment of T1D. In light of these reports, a recent work investigated the potential of artificial extracellular vesicles (aEVs) with the presentation of PD-L1 and Gal-9 ligands (PD-L1-Gal-9 aEVs) as a treatment for T1D, with the findings published in Diabetes. Notably, the PD-L1-Gal-9 aEVs

Applications of Regenerative Tissue-Engineered Scaffolds for Treatment of Spinal Cord Injury.

Tissue engineering provides a path forward for emerging personalized medicine therapies as well as the ability to bring about cures for diseases or chronic injuries. Traumatic spinal cord injuries (SCIs) are an example of a chronic injury in which no cure or complete functional recovery treatment has been developed. In part, this has been due to the complex and interconnected nature of the central nervous system (CNS), the cellular makeup, its extracellular matrix (ECM), and the injury site pathophysiology. One way to combat the complex nature of an SCI has been to create functional tissue-eng…

In situ engineered magnesium alloy implant for preventing postsurgical tumor recurrence.

Invasive tumors are difficult to be completely resected in clinical surgery due to the lack of clear resection margins, which greatly increases the risk of postoperative recurrence. However, chemotherapy and radiotherapy as the traditional means of postoperative adjuvant therapy, are limited in postoperative applications, such as multi-drug resistance and low sensitivity, etc. Therefore, an engineered magnesium alloy rod is designed as a postoperative implant to completely remove postoperative residual tumor tissue and inhibit tumor recurrence by gas and mild magnetic hyperthermia therapy (MMH

Engineered IscB-ωRNA system with expanded target range for base editing.

As the evolutionary ancestor of Cas9 nuclease, IscB proteins serve as compact RNA-guided DNA endonucleases and nickases, making them strong candidates for base editing. Nevertheless, the narrow targeting scope limits the application of IscB systems; thus, it is necessary to find more IscBs that recognize different target-adjacent motifs (TAMs). Here, we identified 10 of 19 uncharacterized IscB proteins from uncultured microbes with activity in mammalian cells. Through protein and ωRNA engineering, we further enhanced the activity of IscB ortholog IscB.m16 and expanded its TAM scope from MRNRAA…

The Role of the Pancreatic Extracellular Matrix as a Tissue Engineering Support for the Bioartificial Pancreas.

Type 1 diabetes mellitus (T1DM) is a chronic condition primarily managed with insulin replacement, leading to significant treatment costs. C … uctural and regulatory functions critical for cell migration, differentiation, and adhesion. Tissue engineering aims to create bioartificial pancreases integrating insulin-producing cells and suitable frameworks. This involves decellularization and recellularization techniques to develop biological scaffolds. The challenges include replicating the pancreas's …

Engineered Peptides Harboring Cation Motifs Against Multidrug-Resistant Bacteria.

Multidrug-resistant (MDR) pathogens pose a serious threat to the health and life of humans, necessitating the development of new antimicrobial agents. Herein, we develop and characterize a panel of nine amino acid peptides with a cation end motif. Bioactivity analysis revealed that the short peptide containing "RWWWR" as a central motif harboring mirror structure "KXR" unit displayed not only high activity against MDR planktonic bacteria but also a clearance rate of 92.33% ± 0.58% against mature biofilm. Mechanically, the target peptide (KLR) killed pathogens by excessively accumulating reacti

An Antibiotic-Degrading Engineered Biofilm Platform to Combat Environmental Antibiotic Resistance.

The presence of antibiotics in natural water bodies is a growing problem regarding the occurrence of antibiotic resistance among various species. This is mainly caused by the excessive use of medical and veterinary antibiotics as well as the lack of effective treatment processes for eliminating residual antibiotics from wastewaters. In this study, we introduce a genetically engineered biomaterial as a solution for the effective degradation of one of the dominantly found antibiotics in natural water bodies. Our biomaterial harnesses laccase-type enzymes, which are known to attack specific types

3D bioprinting of the airways and lungs for applications in tissue engineering and in vitro models.

Tissue engineering and in vitro modeling of the airways and lungs in the respiratory system are of substantial research and clinical importance. In vitro airway and lung models aim to improve treatment options for airway and lung repair and advance respiratory pathophysiological research. The construction of biomimetic native airways and lungs with tissue-specific biological, mechanical, and configurable features remains challenging. Bioprinting, an emerging 3D printing technology, is promising for the development of airway, lung, and disease models, allowing the incorporation of cells and bio…

Molecular Targeting of Ischemic Stroke: The Promise of Naïve and Engineered Extracellular Vesicles.

Ischemic stroke (IS) remains a leading cause of mortality and long-term disability worldwide, with limited therapeutic options available. De … EVs in IS treatment at the molecular level. This review also explores the recent advancements in EV engineering, including the incorporation of specific proteins, RNAs, or pharmacological agents into EVs to enhance their therapeutic efficacy.

Engineered microalgae for photo-sonodynamic synergistic therapy in breast cancer treatment.

Dynamic therapies such as photodynamic therapy (PDT) and sonodynamic therapy (SDT) have potential in cancer treatment. Microalgae have attracted increasing attention because of their high active mobility, flexibility in terms of functionality, and good biocompatibility. In this study, surface-engineered microalgae Chlorella vulgaris (Chl) modified with metal‒organic framework (MOF) nanoparticles (denoted Chl-MOF) are successfully developed for synergistic photo-sonodynamic therapy and immunotherapy. The resulting Chl-MOF can be used as an oxygenator for O2 generation through Chl-mediated photo

A Multiple Attention Convolutional Neural Networks for Diesel Engine Fault Diagnosis.

Fault diagnosis can improve the safety and reliability of diesel engines. An end-to-end method based on a multi-attention convolutional neural network (MACNN) is proposed for accurate and efficient diesel engine fault diagnosis. By optimizing the arrangement and kernel size of the channel and spatial attention modules, the feature extraction capability is improved, and an improved convolutional block attention module (ICBAM) is obtained. Vibration signal features are acquired using a feature extraction model alternating between the convolutional neural network (CNN) and ICBAM. The feature map

Anti-BCMA-engineered exosomes for bortezomib-targeted delivery in multiple myeloma.

AbstractExosomes have emerged as promising vehicles for delivering therapeutic cargoes to specific cells or tissues, owing to their superior biocompatibility, reduced immunogenicity, and enhanced targeting capabilities compared with conventional drug delivery systems. In this study, we developed a delivery platform using exosomes derived from monocytes, specifically designed for targeted delivery of bortezomib (Btz) to multiple myeloma (MM) cells. Our approach involved the genetic modification of monocytes to express antibodies targeting B-cell maturation antigen (anti-BCMA), because BCMA sele

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… Results Engineering exosomes for targeted drug delivery in MM This approach aimed to use the natural targeting properties of exosomes derived from monocytes to specifically deliver therapeutic cargo to myeloma cells expressing BCMA. … The myeloma-targeting capability of exosomes was conferred by engineering the monocytes to express anti-BCMA. …

Engineered mitochondria exert potent antitumor immunity as a cancer vaccine platform.

The preferable antigen delivery profile accompanied by sufficient adjuvants favors vaccine efficiency. Mitochondria, which feature prokaryotic characteristics and contain various damage-associated molecular patterns (DAMPs), are easily taken up by phagocytes and simultaneously activate innate immunity. In the current study, we established a mitochondria engineering platform for generating antigen-enriched mitochondria as cancer vaccine. Ovalbumin (OVA) and tyrosinase-related protein 2 (TRP2) were used as model antigens to synthesize fusion proteins with mitochondria-localized signal peptides. …

A novel engineered strain of Methylorubrum extorquens for methylotrophic production of glycolic acid.

The conversion of CO2 into methanol depicts one of the most promising emerging renewable routes for the chemical and biotech industry. Under this regard, native methylotrophs have a large potential for converting methanol into value-added products but require targeted engineering approaches to enhance their performances and to widen their product spectrum. Here we use a systems-based approach to analyze and engineer M. extorquens TK 0001 for production of glycolic acid. Application of constraint-based metabolic modeling reveals the great potential of M. extorquens for that purpose, which is no…

Molecularly Engineered Supramolecular Thermoresponsive Hydrogels with Tunable Mechanical and Dynamic Properties.

Synthetic supramolecular polymers and hydrogels in water are emerging as promising biomaterials due to their modularity and intrinsic dynamics. Here, we introduce temperature sensitivity into the nonfunctionalized benzene-1,3,5-tricarboxamide (BTA-EG4) supramolecular system by incorporating a poly(N-isopropylacrylamide)-functionalized (BTA-PNIPAM) moiety, enabling 3D cell encapsulation applications. The viscous and structural properties in the solution state as well as the mechanical and dynamic features in the gel state of BTA-PNIPAM/BTA-EG4 mixtures were investigated and modulated. In the di