Diagnosis and Simultaneous Treatment of Musculoskeletal Injury Using H2O2-Triggered Echogenic Antioxidant Polymer Nanoparticles in a Rat Model of Contusion Injury.

Ultrasound is clinically used for diagnosis and interventions for musculoskeletal injuries like muscle contusion, but contrast of ultrasonography still remains a challenge in the field of the musculoskeletal system. A level of hydrogen peroxide (H2O2) is known to be elevated during mechanical tissue damage and therefore H2O2 can be exploited as a diagnostic and therapeutic marker for mechanical injuries in the musculoskeletal system. We previously developed poly(vanillin-oxalate) (PVO) as an inflammation-responsive polymeric prodrug of vanillin, which is designed to rapidly respond to H2O2 and exert antioxidant and anti-inflammatory activities. The primary aim of this study is to verify whether PVO nanoparticles could serve as contrast agents as well as therapeutic agents for musculoskeletal injuries simultaneously. In a rat model of contusion-induced muscle injury, PVO nanoparticles generated CO2 bubbles to enhance the ultrasound contrast in the injury site. A single intramuscular injection of PVO nanoparticles also suppressed contusion-induced muscle damages by inhibiting the expression of pro-inflammatory cytokines and inflammatory cell infiltration. We, therefore, anticipate that PVO nanoparticles have great translational potential as not only ultrasound imaging agents but also therapeutic agents for the musculoskeletal disorders such as contusion.

Correction: Immature dendritic cells navigate microscopic mazes to find tumor cells.

Correction for 'Immature dendritic cells navigate microscopic mazes to find tumor cells' by Eujin Um et al., Lab Chip, 2019, 19, 1665-1675.

Immature dendritic cells navigate microscopic mazes to find tumor cells.

Dendritic cells (DCs) are potent antigen-presenting cells with high sentinel ability to scan their neighborhood and to initiate an adaptive immune response. Whereas chemotactic migration of mature DCs (mDCs) towards lymph nodes is relatively well documented, the migratory behavior of immature DCs (imDCs) in tumor microenvironments is still poorly understood. Here, microfluidic systems of various geometries, including mazes, are used to investigate how the physical and chemical microenvironment influences the migration pattern of imDCs. Under proper degree of confinement, the imDCs are preferentially recruited towards cancer vs. normal cells, accompanied by increased cell speed and persistence. Furthermore, a systematic screen of cytokines, reveals that Gas6 is a major chemokine responsible for the chemotactic preference. These results and the accompanying theoretical model suggest that imDC migration in complex tissue environments is tuned by a proper balance between the strength of the chemical gradients and the degree of spatial confinement.

Three-dimensional culture and interaction of cancer cells and dendritic cells in an electrospun nano-submicron hybrid fibrous scaffold.

An artificial three-dimensional (3D) culture system that mimics the tumor microenvironment in vitro is an essential tool for investigating the cross-talk between immune and cancer cells in tumors. In this study, we developed a 3D culture system using an electrospun poly(ε-caprolactone) (PCL) nanofibrous scaffold (NFS). A hybrid NFS containing an uninterrupted network of nano- and submicron-scale fibers (400 nm to 2 µm) was generated by deposition onto a stainless steel mesh instead of an aluminum plate. The hybrid NFS contained multiplanar pores in a 3D structure. Surface-seeded mouse CT26 colon cancer cells and bone marrow-derived dendritic cells (BM-DCs) were able to infiltrate the hybrid NFS within several hours. BM-DCs cultured on PCL nanofibers showed a baseline inactive form, and lipopolysaccharide (LPS)-activated BM-DCs showed increased expression of CD86 and major histocompatibility complex Class II. Actin and phosphorylated FAK were enriched where unstimulated and LPS-stimulated BM-DCs contacted the fibers in the 3D hybrid NFS. When BM-DCs were cocultured with mitoxantrone-treated CT26 cells in a 3D hybrid NFS, BM-DCs sprouted cytoplasm to, migrated to, synapsed with, and engulfed mitoxantrone-treated CT26 cancer cells, which were similar to the naturally occurring cross-talk between these two types of cells. The 3D hybrid NFS developed here provides a 3D structure for coculture of cancer and immune cells.

Fabrication of electrospun SiC fibers web/phenol resin composites for the application to high thermal conducting substrate.

Polycabosilane (PCS) could be spun to form fiber web by electrospinning PCS solution in 30% dimethylformide (DMF)/toluene solvent at 25 kV. The electrospun web is stabilized at 200 degrees C for 1 hour to connect fibers by softening PCS webs and pyrolysed to synthesize silicon carbide (SiC) webs at 1800 degrees C. The pyrolysis at 1800 degrees C increased the SiC crystal size to 45 nm from 3 nm at 1300 degrees C. However, the pyrolysis at 1800 degrees C forms pores on the surface of SiC fibers due to oxygen evaporation generated during thermals curing. SiC/phenol composite webs could be fabricated by infiltration of phenol resin and hot pressing. The thermal conductivity measurement indicates that higher SiC fibers filler contents increase the thermal conductivity up to 1.9 W/mK for 40% fraction of filler contents from 0.5 W/mK for 20% fraction of filler.

Early estrogen-induced gene 1, a novel RANK signaling component, is essential for osteoclastogenesis.

The receptor activator of NF-κB (RANK) and immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptors are essential factors involved in regulating osteoclast formation and bone remodeling. Here, we identify early estrogen-induced gene 1 (EEIG1) as a novel RANK ligand (RANKL)-inducible protein that physically interacts with RANK and further associates with Gab2, PLCγ2 and Tec/Btk kinases upon RANKL stimulation. EEIG1 positively regulates RANKL-induced osteoclast formation, likely due to its ability to facilitate RANKL-stimulated PLCγ2 phosphorylation and NFATc1 induction. In addition, an inhibitory peptide designed to block RANK-EEIG1 interaction inhibited RANKL-induced bone destruction by reducing osteoclast formation. Together, our results identify EEIG1 as a novel RANK signaling component controlling RANK-mediated osteoclast formation, and suggest that targeting EEIG1 might represent a new therapeutic strategy for the treatment of pathological bone resorption.