In vivo antitumor activity of PHT-427 inhibitor-loaded polymeric nanoparticles in head and neck squamous cell carcinoma.

Recent studies on head and neck squamous cell carcinoma (HNSCC) tumorigenesis have revealed several dysregulated molecular pathways. The phosphatidylinositol-3-kinase (PI3K) signaling pathway is frequently activated in HNSCC, making it an attractive target for therapies. PHT-427 is a dual inhibitor of PI3K and the mammalian target of AKT/PDK1.

Reduction reactions dominate the interactions between Mg alloys and cells: Understanding the mechanisms.

Magnesium (Mg) alloys are popular biodegradable metals studied for orthopedic and cardiovascular applications, mainly because Mg ions are essential trace elements known to promote angiogenesis and osteogenesis. However, Mg corrosion consists of oxidation and reduction reactions that produce by-products, such as hydrogen gas, reactive oxygen species, and hydroxides. It is still unclear how all these by-products and Mg ions concomitantly alter the microenvironment and cell behaviors spatially and temporally.

Vanillic acid-based pro-coagulant hemostatic shape memory polymer foams with antimicrobial properties against drug-resistant bacteria.

Uncontrolled bleeding is the primary cause of trauma-related death. For patients that are brought to the hospital in time to receive treatment, there is a great risk of contracting drug-resistant bacterial wound infections. Therefore, low-cost hemostatic agents with procoagulant and antibacterial properties are essential to reduce morbidity and mortality in patients with traumatic wounds.

3D micro-CT and O-PTIR spectroscopy bring new understanding of the influence of filler content in dental resin composites.

Background: Dental resin composites' performance is intricately linked to their polymerisation shrinkage characteristics. This study compares polymerisation shrinkage using advanced 3D micro-computed tomography (micro-CT) and traditional 2D linear assessments. It delves into the crucial role of filler content on shrinkage and the degree of conversion in dental resin composites, providing valuable insights for the field.

PI3K/AKT/mTOR signaling regulates BCP ceramic-induced osteogenesis.

An increasing number of studies demonstrate that biphasic calcium phosphate (BCP) ceramics can induce bone regeneration. However, the underlying molecular mechanisms involved are still poorly understood. This work was proposed to investigate how PI3K/AKT/mTOR signaling influenced the osteogenesis mediated by BCP ceramics.

Static Behavior of a 3D-Printed Short Carbon Fiber Polyamide: Influence of the Meso-Structure and Water Content.

The knowledge of the mechanical behavior of a 3D-printed material is fundamental for the 3D printing outbreaking technology to be considered for a range of applications. In this framework, the significance, reliability, and accuracy of the information obtained by testing material coupons assumes a pivotal role. The present work focuses on an evaluation of the static mechanical properties and failure modes of a 3D-printed short carbon fiber-reinforced polyamide in relation to the specimen's unique meso-structural morphology and water content.

Chitosan Poly(vinyl alcohol) Methacrylate Hydrogels for Tissue Engineering Scaffolds.

A major challenge in tissue engineering scaffolds is controlling scaffold degradation rates during healing while maintaining mechanical properties to support tissue formation. Hydrogels are three-dimensional matrices that are widely applied as tissue scaffolds based on their unique properties that can mimic the extracellular matrix. In this study, we develop a hybrid natural/synthetic hydrogel platform to tune the properties for tissue engineering scaffold applications.

Self-Defensive Antimicrobial Shape Memory Polyurethanes with Honey-Based Compounds.

Infection treatment plays a crucial role in aiding the body in wound healing. To that end, we developed a library of antimicrobial polymers based on segmented shape memory polyurethanes with nondrug-based antimicrobials (i.e.

The role of toll-like receptors in orchestrating osteogenic differentiation of mesenchymal stromal cells and osteoimmunology.

Osteoimmunology is a concept involving molecular and cellular crosstalk between the skeletal and immune systems. Toll-like receptors (TLRs) are widely expressed both on mesenchymal stromal cells (MSCs), the hematopoietic cells, and immune cells in the osteogenic microenvironment for bone development or repair. TLRs can sense both exogenous pathogen-associated molecular patterns (PAMPs) derived from microorganisms, and damage-associated molecular patterns (DAMPs) derived from normal cells subjected to injury, inflammation, or cell apoptosis under physiological or pathological conditions.

Osteocyte-Like Cells Differentiated From Primary Osteoblasts in an Artificial Human Bone Tissue Model.

In vitro models of primary human osteocytes embedded in natural mineralized matrix without artificial scaffolds are lacking. We have established cell culture conditions that favored the natural 3D orientation of the bone cells and stimulated the cascade of signaling needed for primary human osteoblasts to differentiate into osteocytes with the characteristically phenotypical dendritic network between cells. Primary human osteoblasts cultured in a 3D rotating bioreactor and incubated with a combination of vitamins A, C, and D for up to 21 days produced osteospheres resembling native bone.

Aspect ratio-dependent dual-regulation of the tumor immune microenvironment against osteosarcoma by hydroxyapatite nanoparticles.

Accumulating studies demonstrated that hydroxyapatite nanoparticles (HANPs) showed a selective anti-tumor effect, making them a good candidate for osteosarcoma (OS) treatment. However, the capacity of HANPs with different aspect ratios to regulate tumor immune microenvironment (TIM) was scarcely reported before. To explore it, the three HANPs with aspect ratios from 1.

Hydroxyapatite nanoparticles promote TLR4 agonist-mediated anti-tumor immunity through synergically enhanced macrophage polarization.

Macrophages represent the most prevalent immune cells in the tumor micro-environment, making them an appealing target for tumor immunotherapy. One of our previous studies showed that hydroxyapatite nanoparticles (HANPs) enhanced Toll-like receptor 4 (TLR4) signal transduction in macrophages. This study was proposed to investigate how HANPs manipulated the phenotype and function of macrophage against 4T1 breast tumors in the presence or absence of MPLA, a low toxic Toll-like receptor 4 (TLR4) agonist.

Preliminary Stiffness-Driven Redesign of a Laminated Prosthetic Component Using Additive Manufacturing.

Three-dimensional printed polymers offer unprecedented advantages for prosthetic applications, namely in terms of affordability and customisation. This work thus investigates the possibility of designing an additively manufactured prosthetic foot using continuous fibre-reinforced polymers as an alternative to composite laminate ones. A numerical approach was thus proposed and validated as a possible design tool for additively manufactured composite feet.

model to study confined osteocyte networks exposed to flow-induced mechanical stimuli.

Osteocytes are considered the primary mechanical sensor in bone tissue and orchestrate the coupled bone remodeling activity of adjacent osteoblast and osteoclast cells.investigation of mechanically induced signal propagation through networks of interconnected osteocytes is confounded by their confinement within the mineralized bone matrix, which cannot be modeled in conventional culture systems. In this study, we developed a new model that mimics thisconfinement using gelatin methacrylate (GelMA) hydrogel or GelMA mineralized using osteoblast-like model cells.

A Selective Reduction of Osteosarcoma by Mitochondrial Apoptosis Using Hydroxyapatite Nanoparticles.

Background: In recent years, using hydroxyapatite nanoparticles (HANPs) for tumor therapy attracted increasing attention because HANPs were found to selectively suppress the growth of tumor cells but exhibit ignorable toxicity to normal cells.

Purpose: This study aimed to investigate the capacities of HANPs with different morphologies and particle sizes against two kinds of osteosarcoma (OS) cells, human OS 143B cells and rat OS UMR106 cells.

Methods: Six kinds of HANPs with different morphologies and particle sizes were prepared by wet chemical method.

Hydroxyapatite nanoparticles drive the potency of Toll-like receptor 9 agonist for amplified innate and adaptive immune response.

Unlabelled: The potency of Toll-like receptor 9 (TLR9) agonist to drive innate immune response was limited due to immune suppression or tolerance during TLR9 signaling activation in immune cells. Herein we addressed this problem by introducing hydroxyapatite nanoparticles (HANPs) to CpG ODN (CpG), a TLR9 agonist. The study revealed that HANPs concentration and duration-dependently reprogramed the immune response by enhancing the secretion of immunostimulatory cytokines (tumor necrosis factor α (TNFα) or IL-6) while reducing the production of immunosuppressive cytokine (IL-10) in macrophages in response to CpG.

Design and clinical application of injectable hydrogels for musculoskeletal therapy.

Musculoskeletal defects are an enormous healthcare burden and source of pain and disability for individuals. With an aging population, the proportion of individuals living with these medical indications will increase. Simultaneously, there is pressure on healthcare providers to source efficient solutions, which are cheaper and less invasive than conventional technology.

Long-term fretting corrosion performance of modular head-neck junctions with self-reinforced composite gaskets from PEEK and UHMWPE.

Soft gasket-like polymer films may provide multiple advantages in inhibiting fretting corrosion between metal-hard surfaces in total joint implants. Self-reinforced composites (SRC's) made from either poly(ether ether ketone), SRC-PEEK, or ultra high molecular weight polyethylene, SRC-PE, were fabricated and tested to investigate their ability to limit or prevent mechanically assisted corrosion in modular taper devices. Hot compaction was used to create nominally 100 μm thick unidirectional composite gaskets.

Biostable Shape Memory Polymer Foams for Smart Biomaterial Applications.

Polyurethane foams provide a wide range of applications as a biomaterial system due to the ability to tune their physical, chemical, and biological properties to meet the requirements of the intended applications. Another key parameter that determines the usability of this biomaterial is its degradability under body conditions. Several current approaches focus on slowing the degradation rate for applications that require the implant to be present for a longer time frame (over 100 days).

Superhydrophobic Polymer Composite Surfaces Developed via Photopolymerization.

Fabrication of superhydrophobic materials using incumbent techniques involves several processing steps and is therefore either quite complex, not scalable, or often both. Here, the development of superhydrophobic surface-patterned polymer-TiO composite materials using a simple, single-step photopolymerization-based approach is reported. The synergistic combination of concurrent, periodic bump-like pattern formation created using irradiation through a photomask and photopolymerization-induced nanoparticle (NP) phase separation enables the development of surface textures with dual-scale roughness (micrometer-sized bumps and NPs) that demonstrate high water contact angles, low roll-off angles, and desirable postprocessability such as flexibility, peel-and-stick capability, and self-cleaning capability.

Exposure to hydroxyapatite nanoparticles enhances Toll-like receptor 4 signal transduction and overcomes endotoxin tolerance in vitro and in vivo.

Emerging studies indicate hydroxyapatite nanoparticles (HANPs) exhibit modest immunogenicity to elicit innate immune response which might involve Toll-like receptor 4 (TLR4) activation. This study was proposed to elucidate how HANPs direct over TLR4 signal activity in macrophage in response to TLR4 ligand, lipopolysaccharide (LPS). The present study for the first time reveals that HANPs themselves can induce TLR4 endocytosis and activate pathways both of nuclear factor-kappa B (NF-κB) and interferon regulatory factor 3 (IRF3), which potentially trigger the production of inflammatory cytokine by macrophage.

Antitumor Activity of Nanoparticles Loaded with PHT-427, a Novel AKT/PDK1 Inhibitor, for the Treatment of Head and Neck Squamous Cell Carcinoma.

Currently, new treatments are required to supplement the current standard of care for head and neck squamous cell carcinoma (HNSCC). The phosphatidylinositol3-kinase (PI3K) signaling pathway is commonly altered and activated in HNSCC. PHT-427 is a dual PI3K-mammalian target of the AKT/PDK1 inhibitor; however, to the best of our knowledge, the effect of the PHT-427 inhibitor on HNSCC has not been investigated.

Paclitaxel-loaded polymeric nanoparticles based on α-tocopheryl succinate for the treatment of head and neck squamous cell carcinoma: murine model.

The prognosis of patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC) is generally poor. New treatments are required to supplement the current standard of care. Paclitaxel (PTX), an effective chemotherapeutic for HNSCC, has serious side effects.

The effect of hypochlorous acid on the tribocorrosion of CoCrMo/Ti-6Al-4V bearing couples.

Mechanically assisted corrosion (MAC) of metallic orthopedic alloys is a consequence of the use of modular devices where opposing metal surfaces are tightly mated and loaded at the taper junction. MAC processes are affected by material surface characteristics and local solution chemistry. During inflammation, active immune cells may generate reactive oxygen species (such as hypochlorous acid [HOCl]) adjacent to surfaces undergoing micromotion, which may affect the tribocorrosion behavior of an implanted device.