M1 macrophage-derived exosomal microRNA-29c-3p suppresses aggressiveness of melanoma cells via ENPP2.

In the tumor microenvironment, macrophages play crucial roles resulting in tumor suppression and progression, depending on M1 and M2 macrophages, respectively. In particular, macrophage-derived exosomes modulate the gene expression of cancer cells by delivering miRNAs which downregulate specific genes. The communication between macrophages and cancer cells is especially important in immunogenic tumors such as melanoma, where the cancer pogression is significantly influenced by the surrounding immune cells.

TRPA1 nanovesicle-conjugated receptonics for rapid biocide screening.

Although biocides are important materials in modern society and help protect human health and the environment, increasing exposure to combined biocides can cause severe side effects in the human body, such as lung fibrosis. In this study, we developed a receptonics system to screen for biocides in combined household chemical products based on biocides. The system contains transient receptor potential ankyrin 1 (TRPA1) nanovesicles (NVs) to sense biocides based on pain receptors and a side-gated field-effect transistor (SGFET) using a single-layer graphene (SLG) micropattern channel.

A micro-fragmented collagen gel as a cell-assembling platform for critical limb ischemia repair.

Critical limb ischemia (CLI) is a devastating disease characterized by the progressive blockage of blood vessels. Although the paracrine effect of growth factors in stem cell therapy made it a promising angiogenic therapy for CLI, poor cell survival in the harsh ischemic microenvironment limited its efficacy. Thus, an imperative need exists for a stem-cell delivery method that enhances cell survival.

Effective protection of photoreceptors using an inflammation-responsive hydrogel to attenuate outer retinal degeneration.

Retinitis pigmentosa (RP) is an outer retinal degenerative disease that can lead to photoreceptor cell death and profound vision loss. Although effective regulation of intraretinal inflammation can slow down the progression of the disease, an efficient anti-inflammatory treatment strategy is still lacking. This study reports the fabrication of a hyaluronic acid-based inflammation-responsive hydrogel (IRH) and its epigenetic regulation effects on retinal degeneration.

Artificial intelligence-driven new drug discovery targeting serine/threonine kinase 33 for cancer treatment.

Background: Artificial intelligence (AI) is capable of integrating a large amount of related information to predict therapeutic relationships such as disease treatment with known drugs, gene expression, and drug-target binding. AI has gained increasing attention as a promising tool for next-generation drug development.

Methods: An AI method was used for drug repurposing and target identification for cancer.

Eye-Mimicked Neural Network Composed of Photosensitive Neural Spheroids with Human Opsin Proteins.

An in vitro model, composed of the short-wavelength human opsins and rhodopsins, is created. Two types of photosensitive neural spheroids are transfected for selective reaction under bluish-purple and green lights. These are employed to two devices with intact neuron and neural-spheroid to study the interaction.

Functionally enhanced cell spheroids for stem cell therapy: Role of TIMP1 in the survival and therapeutic effectiveness of stem cell spheroids.

Stem cell therapy has emerged as a promising regenerative medicine strategy but is limited by poor cell survival, leading to low therapeutic outcomes. We developed cell spheroid therapeutics to overcome this limitation. We utilized solid-phase FGF2 to form functionally enhanced cell spheroid-adipose derived (FECS-Ad), a type of cell spheroid that preconditions cells with intrinsic hypoxia to increase the survival of transplanted cells.

Hydrogel/Nanofiber Composite Wound Dressing Optimized for Skin Layer Regeneration through the Mechanotransduction-Based Microcellular Environment.

Wound dressings have been designed to provide the optimal environment to fibroblasts, keratinocytes, and macrophages to promote wound healing while inhibiting potential microbial infection. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel with a gelatin backbone that contains natural cell binding motifs such as arginine-glycine-aspartic acid (RGD) and MMP-sensitive degradation sites, making it an ideal material for wound dressing. However, GelMA alone is unable to stably protect the wound and regulate cellular activities due to its weak mechanical properties and nonmicropatterned surface, limiting its application as a wound dressing.

Facile construction of tumour spheroids with induced M2 macrophage polarization for anticancer drug screening.

Tumour-associated macrophages (TAMs) are involved in cancer progression and drug resistance in the tumour microenvironment (TME). Consequently, macrophages as therapeutic targets have garnered increased attention; however, there are hurdles to screening interactions between cancer and macrophages owing to technical difficulties in recapitulatingphysiological systems. In this study, we propose a simple strategy to construct tumour spheroids with induced M2 macrophage polarization for anticancer drug screening.

Fibroblasts Close a Void in Free Space by a Purse-String Mechanism.

The mechanism by which stromal cells fill voids in injured tissue remains a fundamental question in regenerative medicine. While it is well-established that fibroblasts fill voids by depositing extracellular matrix (ECM) proteins as they migrate toward the wound site, little is known about their ability to adopt an epithelial-like purse-string behavior. To investigate fibroblast behavior during gap closure, we created an artificial wound with a large void space.

Cytosolic microRNA-inducible nuclear translocation of Cas9 protein for disease-specific genome modification.

MicroRNA-dependent mRNA decay plays an important role in gene silencing by facilitating posttranscriptional and translational repression. Inspired by this intrinsic nature of microRNA-mediated mRNA cleavage, here, we describe a microRNA-targeting mRNA as a switch platform called mRNA bridge mimetics to regulate the translocation of proteins. We applied the mRNA bridge mimetics platform to Cas9 protein to confer it the ability to translocate into the nucleus via cleavage of the nuclear export signal.

TIMP-1-expressing breast tumor spheroids for the evaluation of drug penetration and efficacy.

Abundance of stromal cells and extracellular matrix (ECM) is observed in breast cancer, acting as a barrier for drug penetration and presenting a key issue for developing efficient therapeutics. In this study, we aimed to develop a three-dimensional (3D) multicellular tumor model comprising cancer and stromal cells that could effectively mimic the drug resistance properties of breast cancer. Three different types of spheroid models were designed by co-culturing breast cancer cells (MDA-MB-231) with three different types of stromal cells: human adipose-derived stromal cells (hASCs), human bone marrow stromal cells, or human dermal fibroblasts.

On-Demand Local Immunomodulation via Epigenetic Control of Macrophages Using an Inflammation-Responsive Hydrogel for Accelerated Wound Healing.

Effective resolution of inflammation contributes to favorable tissue regenerative therapeutic outcomes. However, fine coordination of local immunomodulation in a timely manner is limited because of the lack of strategies for controlling disease dynamics. We developed an inflammation-responsive hydrogel (IFRep gel) as an effective therapeutic strategy for on-demand epigenetic modulation against disease dynamics in wound healing.

FGF2-primed 3D spheroids producing IL-8 promote therapeutic angiogenesis in murine hindlimb ischemia.

Peripheral artery disease is a progressive, devastating disease that leads to critical limb ischemia (CLI). Therapeutic angiogenesis using stem cell therapy has emerged as a promising approach for its treatment; however, adapting cell-based therapy has been limited by poor cell survival and low treatment efficiency. To overcome unmet clinical needs, we developed a fibroblast growth factor 2 (FGF2)-immobilized matrix that enabled control of cell adhesion to the surface and exerted a priming effect on the cell.

Acetate decreases PVR/CD155 expression via PI3K/AKT pathway in cancer cells.

In recent years, restoring anti-tumor immunity has garnered a growing interest in cancer treatment. As potential therapeutics, immune checkpoint inhibitors have demonstrated benefits in many clinical studies. Although various methods have been applied to suppress immune checkpoints to boost anti-tumor immunity, including the use of immune checkpoint inhibitors, there are still unmet clinical needs to improve the response rate of cancer treatment.

Exosomal miRNA-19a and miRNA-614 Induced by Air Pollutants Promote Proinflammatory M1 Macrophage Polarization via Regulation of RORα Expression in Human Respiratory Mucosal Microenvironment.

Air pollution exposure leads to various inflammatory diseases in the human respiratory system. Chronic rhinosinusitis is an inflammatory disease caused by viruses, bacteria, or air pollutants. However, the underlying molecular mechanisms through which air particulate matter (PM) causes inflammation and disease remain unclear.

Combinatorial Inhibition of Cell Surface Receptors Using Dual Aptamer-Functionalized Nanoconstructs for Cancer Treatment.

Membrane receptors overexpressed in diseased states are considered novel therapeutic targets. However, the single targeting approach faces several fundamental issues, such as poor efficacy, resistance, and toxicity. Here, we report a dual-targeting strategy to enhance anti-cancer efficacy via synergistic proximity interactions between therapeutics and two receptor proteins.

RORα Regulates Cholesterol Metabolism of CD8 T Cells for Anticancer Immunity.

Retinoic acid-related orphan receptor α (RORα) functions as a transcription factor for various biological processes, including circadian rhythm, inflammation, cancer, and lipid metabolism. Here, we demonstrate that RORα is crucial for maintaining cholesterol homeostasis in CD8 T cells by attenuating NF-kB transcriptional activity. Cholesterol sulfate, the established natural agonist of RORα, exhibits cellular cytotoxicity on, and increased effector responses in, CD8 T cells.

Self-Organized Liver Microtissue on a Bio-Functional Surface: The Role of Human Adipose-Derived Stromal Cells in Hepatic Function.

The maintenance of hepatocyte function is a critical research topic in liver tissue engineering. Although an increasing number of strategies have been developed, liver tissue engineering using hepatocytes as a therapeutic alternative remains challenging owing to its poor efficacy. In this study, we developed a multicellular hepatic microtissue to enhance the function of induced hepatic precursor cells.

Machine learning-based design strategy for 3D printable bioink: elastic modulus and yield stress determine printability.

Although three-dimensional (3D) bioprinting technology is rapidly developing, the design strategies for biocompatible 3D-printable bioinks remain a challenge. In this study, we developed a machine learning-based method to design 3D-printable bioink using a model system with naturally derived biomaterials. First, we demonstrated that atelocollagen (AC) has desirable physical properties for printing compared to native collagen (NC).

Fabrication of 3D plotted scaffold with microporous strands for bone tissue engineering.

Scaffold porosity has played a key role in bone tissue engineering aimed at effective tissue regeneration, by promoting cell attachment, proliferation, and osteogenic differentiation for new bone formation. Three-dimensional plotting systems (3DPSs) have been widely used to introduce porosity to the scaffold; however, introducing certain features in the scaffold strands that improve bone tissue regeneration remains a challenge. In this work, we fabricated bone tissue scaffolds with macro- and microporous structural features using a 3DPS and non-solvent-induced phase separation method.

Identification of urban particulate matter-induced disruption of human respiratory mucosa integrity using whole transcriptome analysis and organ-on-a chip.

Background: Exposure to air particulate matter (PM) is associated with various diseases in the human respiratory system. To date, most in vitro studies showing cellular responses to PM have been performed in cell culture using a single cell type. There are few studies considering how multicellular networks communicate in a tissue microenvironment when responding to the presence of PM.

Boiling Histotripsy-induced Partial Mechanical Ablation Modulates Tumour Microenvironment by Promoting Immunogenic Cell Death of Cancers.

Boiling histotripsy is a promising non-invasive High-Intensity Focused Ultrasound (HIFU) technique that employs HIFU mechanical effects to fractionate solid tumours without causing any significant thermal damage. It has been suggested that boiling histotripsy may induce a strong immune response due to the absence of denatured antigenic protein at the HIFU focus. The underlying immunological mechanisms of this technique are, however, poorly understood.

Effect of chain flexibility on cell adhesion: Semi-flexible model-based analysis of cell adhesion to hydrogels.

Hydrogels have been developed and applied to various biomedical applications due to their biocompatibility. However, understanding of modulation between cells to hydrogel interface is still unclear, and parameters to explain the interaction are not sophisticated enough. In this report, we studied the effect of polymer chain flexibility on cell adhesion to various hydrogel constructs of collagen and fibrin gels.

Novel skin patch combining human fibroblast-derived matrix and ciprofloxacin for infected wound healing.

Skin injuries are frequently encountered in daily life, but deep wounds often poorly self-heal and do not recover completely. In this study, we propose a novel skin patch that combines antibiotic, cell-derived extracellular matrix (ECM) and biocompatible polyvinyl alcohol (PVA) hydrogel. Decellularized human lung fibroblast-derived matrix (hFDM) was prepared on tissue culture plate (TCP) and PVA solution was then poured onto it.