Mexenone protects mice from LPS-induced sepsis by EC barrier stabilization.

Blood vessels permit the selective passage of molecules and immune cells between tissues and circulation. Uncontrolled inflammatory responses from an infection can increase vascular permeability and edema, which can occasionally lead to fatal organ failure. We identified mexenone as a vascular permeability blocker by testing 2,910 compounds in the Clinically Applied Compound Library using the lipopolysaccharide (LPS)-induced vascular permeability assay.

Assessment of Esophageal Reconstruction via Bioreactor Cultivation of a Synthetic Scaffold in a Canine Model.

Objectives: Using tissue-engineered materials for esophageal reconstruction is a technically challenging task in animals that requires bioreactor training to enhance cellular reactivity. There have been many attempts at esophageal tissue engineering, but the success rate has been limited due to difficulty in initial epithelialization in the special environment of peristalsis. The purpose of this study was to evaluate the potential of an artificial esophagus that can enhance the regeneration of esophageal mucosa and muscle through the optimal combination of a double-layered polymeric scaffold and a custom-designed mesenchymal stem cell-based bioreactor system in a canine model.

Alternative non-oral nutrition in a rat model: a novel modified gastrostomy technique.

The gastrostomy technique is essential for esophageal reconstruction using a scaffold. To date, there are no established methods to supply nutrients through a gastrostomy tube in rats. The purpose of this study was to analyze the feasibility of a newly modified gastrostomy technique for non-oral nutrition in an adult rat model.

Combined Application of Prototype Ultrasound and BSA-Loaded PLGA Particles for Protein Delivery.

Purpose: To develop an in vitro culture system for tissue engineering to mimic the in vivo environment and evaluate the applicability of ultrasound and PLGA particle system.

Methods: For tissue engineering, large molecules such as growth factors for cell differentiation should be supplied in a controlled manner into the culture system, and the in vivo microenvironment need to be reproduced in the system for the regulation of cellular function. In this study, portable prototype ultrasound with low intensity was devised and tested for protein release from bovine serum albumin (BSA)-loaded poly(lactic-co-glycolic acid) (PLGA) particles.

Synergistic Effect of Growth Factor Releasing Polymeric Nanoparticles and Ultrasound Stimulation on Osteogenic Differentiation.

Mesenchymal stem cells (MSCs) have been extensively used in the tissue regeneration therapy. Ex vivo therapy with well-differentiated osteogenic cells is known as an efficient treatment for musculoskeletal diseases, including rheumatoid diseases. However, along with its high cost, the current therapy has limitations in terms of restoring bone regeneration procedures.

Experimental investigation of esophageal reconstruction with electrospun polyurethane nanofiber and 3D printing polycaprolactone scaffolds using a rat model.

Background: We evaluated the outcome of esophageal reconstructions using tissue-engineered scaffolds.

Method: Partial esophageal defects were reconstructed with the following scaffolds; animals were grouped (n = 7 per group) as follows: (a) normal rats; (b) rats implanted with three-dimensional printing (3DP) polycaprolactone (PCL) scaffolds; (c) with human adipose-derived mesenchymal stem cell (ADSC)-seeded 3DP PCL scaffolds; (d) with polyurethane (PU)-nanofiber(Nf) scaffolds; and (e) with ADSC-seeded PU-Nf scaffolds.

Results: The esophageal defects were successfully repaired; however, muscle regeneration was greater in the 3DP PCL + ADSC groups than in the PU-Nf + ADSC groups (P < .

Tissue-Engineered Graft for Circumferential Esophageal Reconstruction in Rats.

The use of biocompatible materials for circumferential esophageal reconstruction is a technically challenging task in rats and requires an optimal implant technique with nutritional support. Recently, there have been many attempts at esophageal tissue engineering, but the success rate has been limited due to difficulty in early epithelization in the special environment of peristalsis. Here, we developed an artificial esophagus that can improve the regeneration of the esophageal mucosa and muscle layers through a two-layered tubular scaffold, a mesenchymal stem cell-based bioreactor system, and a bypass feeding technique with modified gastrostomy.

A Platform for Studying of the Three-Dimensional Migration of Hematopoietic Stem/Progenitor Cells.

Background: Hematopoietic stem/progenitor cells (HSPCs) have the property to return to the bone marrow, which is believed to be critical in situations such as HSPC transplantation. This property plays an important role in the stemness, viability, and proliferation of HSPCs, also. However, most in vitro models so far have not sufficiently simulated the complicate environment.

Influences of sodium tantalite submicro-particles in polyetheretherketone based composites on behaviors of rBMSCs/HGE-1 cells for dental application.

Dental implanted materials require excellent mechanical properties, biocompatibility as well as integration with bone tissue and gingival tissue to achieve early loading and long-term stability. In this study, cubic shape sodium tantalite (ST) submicro-particles with the size of around 180 nm were synthesized by a hydrothermal method, and ST/polyetheretherketone (PEEK) composites (TPC) with ST content of 20 w% (TPC20) and 40 w% (TPC40) were prepared by melting blend. The results showed that the compressive strength, thermal properties, surface roughness, hydrophilicity and surface energy as well as adsorption of proteins on TPC40 were also significantly enhanced compared with TPC20 and PEEK.

Mechanical stimuli enhance simultaneous differentiation into oesophageal cell lineages in a double-layered tubular scaffold.

The tissue-engineered oesophagus serves as an alternative and promising therapeutic approach for long-gap oesophageal replacement. This study proposes an advanced in vitro culture platform focused on construction of the oesophagus by combining an electrospun double-layered tubular scaffold, stem cells, biochemical reagents, and biomechanical factors. Human mesenchymal stem cells were seeded onto the inner and outer surfaces of the scaffold.

The combined effects of hierarchical scaffolds and mechanical stimuli on ex vivo expansion of haematopoietic stem/progenitor cells.

We describe the ex vivo expansion of haematopoietic stem/progenitor cells (HSPCs) with consideration of their eventual in-vivo niche. We firstly fabricated hierarchically structured scaffolds (lattices derived via three-dimensional plotting combined with electrospun submicron fibers coated with vitronectin to increase cell affinity). We also applied intermittent hydrostatic pressure (IHP) to mimic the physical environment of the in vivo niche.

Tissue-Engineered Esophagus via Bioreactor Cultivation for Circumferential Esophageal Reconstruction.

The use of biomaterials for circumferential esophageal repair is technically challenging in a rat model, and an optimal scaffold implantation technique with nutritional support is essential. The purpose of this study was to investigate the effects of three-dimensional printed esophageal grafts and bioreactor cultivation on muscle regeneration and reepithelialization from circumferential esophageal defects in a rat model. Here, we designed an artificial esophagus that can enhance the regeneration of esophageal mucosa and muscle through the optimal combination of a two-layered tubular scaffold and mesenchymal stem cell-based bioreactor system.

Combinational effects of mechanical forces and substrate surface characteristics on esophageal epithelial differentiation.

Even the efficacy of substrate and mechanical stimuli in addition to biochemical cues have been recognized in many studies of stem cell differentiation, few studies have been reported on the differentiation into esophageal epithelial cells. Therefore, the aim of this study was set to propose a method of differentiating stem cells into esophageal epithelial cells according to biochemical reagent concentration, substrate properties, and mechanical forces. After the concentration of all-trans retinoic acid was determined as 5 μM by a baseline experiment, the degree of differentiation was compared in three different kinds of substrates: cover glass, polyurethane (PU) membrane, and electrospun PU sheet (ePU).

Cyclic stretch increases mitochondrial biogenesis in a cardiac cell line.

Unlike stable and immobile cell line conditions, animal hearts contract and relax to pump blood throughout the body. Mitochondria play an essential role by producing biological energy molecules to maintain heart function. In this study, we assessed the effect of heart mimetic cyclic stretch on mitochondria in a cardiac cell line.

Characterization and osteogenic evaluation of mesoporous magnesium-calcium silicate/polycaprolactone/polybutylene succinate composite scaffolds fabricated by rapid prototyping.

The properties of scaffolds for bone tissue engineering, including their biocompatibility, highly interconnected porosity, and mechanical integrity, are critical for promoting cell adhesion, proliferation, and osteoinduction. We used various physical and biological assays to obtain confirmation that the proposed composite scaffolds are potentially suitable for applications to bone tissue engineering. The proposed new composite scaffolds, which we fabricated by a rapid prototyping technique, were composed of mesoporous magnesium-calcium silicate (m_MCS), polycaprolactone (PCL), and polybutylene succinate (PBSu).

Synergistic Integration of Mesenchymal Stem Cells and Hydrostatic Pressure in the Expansion and Maintenance of Human Hematopoietic/Progenitor Cells.

Ex vivo expansion of hematopoietic stem/progenitor cell (HSPC) has been investigated to improve the clinical outcome of HSPC transplantation. However, ex vivo expansion of HSPCs still faces a major obstacle in that HPSCs tend to differentiate when proliferating. Here, we cocultured HSPCs with mesenchymal stem cells (MSCs) and divided the HSPCs into two fractions according to whether they came into adherent to MSCs or not.

Enhanced biocompatibility and osteogenic potential of mesoporous magnesium silicate/polycaprolactone/wheat protein composite scaffolds.

Background: Successful bone tissue engineering using scaffolds is primarily dependent on the properties of the scaffold, including biocompatibility, highly interconnected porosity, and mechanical integrity.

Methods: In this study, we propose new composite scaffolds consisting of mesoporous magnesium silicate (m_MS), polycaprolactone (PCL), and wheat protein (WP) manufactured by a rapid prototyping technique to provide a micro/macro porous structure. Experimental groups were set based on the component ratio: (1) WP0% (m_MS:PCL:WP =30:70:0 weight per weight; w/w); (2) WP15% (m_MS:PCL:WP =30:55:15 w/w); (3) WP30% (m_MS:PCL:WP =30:40:30 w/w).

Influences of mesoporous magnesium calcium silicate on mineralization, degradability, cell responses, curcumin release from macro-mesoporous scaffolds of gliadin based biocomposites.

Macro-mesoporous scaffolds based on wheat gliadin (WG)/mesoporous magnesium calcium silicate (m-MCS) biocomposites (WMC) were developed for bone tissue regeneration. The increasing amount of m-MCS significantly improved the mesoporosity and water absorption of WMC scaffolds while slightly decreased their compressive strength. With the increase of m-MCS content, the degradability of WMC scaffolds was obviously enhanced, and the decrease of pH value could be slow down after soaking in Tris-HCl solution for different time.

In vitro study on anti-inflammatory effects of epigallocatechin-3-gallate-loaded nano- and microscale particles.

Purpose: This study aimed to develop an anti-inflammation system consisting of epigallo-catechin-3-gallate (EGCG) encapsulated in poly(lactide-co-glycolic acid) (PLGA) particles to promote wound healing.

Methods: Nano- and microscale PLGA particles were fabricated using a water/oil/water emulsion solvent evaporation method. The optimal particle size was determined based on drug delivery efficiency and biocompatibility.

PCL/β-TCP Composite Scaffolds Exhibit Positive Osteogenic Differentiation with Mechanical Stimulation.

We investigated the use of Polycaprolactone (PCL)/ β-tricalcium phosphate (β-TCP) composites with applied mechanical stimulation as scaffold for bone tissue engineering. PCL-based three-dimensional (3D) structures were fabricated in a solvent-free process using a 3D-printing technique. The mass fraction of β-TCP was varied in the range 0-30%, and the structure and compressive modulus of the specimens was characterized.

Effects of mechanical stimulation on the reprogramming of somatic cells into human-induced pluripotent stem cells.

Background: Mechanical stimuli play important roles in the proliferation and differentiation of adult stem cells. However, few studies on their effects on induced pluripotent stem cells (iPSCs) have been published.

Methods: Human dermal fibroblasts were seeded onto flexible membrane-bottom plates, and infected with retrovirus expressing the four reprogramming factors OCT4, SOX2, KLF, and c-MYC (OSKM).

Nanoporosity improved water absorption, in vitro degradability, mineralization, osteoblast responses and drug release of poly(butylene succinate)-based composite scaffolds containing nanoporous magnesium silicate compared with magnesium silicate.

Bioactive composite macroporous scaffold containing nanoporosity was prepared by incorporation of nanoporous magnesium silicate (NMS) into poly(butylene succinate) (PBSu) using solvent casting-particulate leaching method. The results showed that the water absorption and in vitro degradability of NMS/PBSu composite (NMPC) scaffold significantly improved compared with magnesium silicate (MS)/PBSu composite (MPC) scaffold. In addition, the NMPC scaffold showed improved apatite mineralization ability, indicating better bioactivity, as the NMPC containing nanoporosity could induce more apatite and homogeneous apatite layer on the surfaces than MPC scaffold.

Mechanical stimuli modulate intracellular calcium oscillations: a pathological model without chemical cues.

Objective: To control the oscillatory behavior of the intracellular calcium ([Ca]) concentration in endothelial cells via mechanical factors (i.e., various hydrostatic pressures) because [Ca] in these cells is affected by blood pressure.