A microscale 3D organ on a chip for recapitulating reciprocal neuroendocrine crosstalk between the hypothalamus and the pituitary gland.

Conventional 2D or even recently developed 3Din vitroculture models for hypothalamus and pituitary gland cannot successfully recapitulate reciprocal neuroendocrine communications between these two pivotal neuroendocrine tissues known to play an essential role in controlling the body's endocrine system, survival, and reproduction. In addition, most currentvitroculture models for neuroendocrine tissues fail to properly reflect their complex multicellular structure. In this context, we developed a novel microscale chip platform, termed the 'hypothalamic-pituitary (HP) axis-on-a-chip,' which integrates various cellular components of the hypothalamus and pituitary gland with biomaterials such as collagen and hyaluronic acid. We used non-toxic blood coagulation factors (fibrinogen and thrombin) as natural cross-linking agents to increase the mechanical strength of biomaterials without showing residual toxicity to overcome drawbacks of conventional chemical cross-linking agents. Furthermore, we identified and verified SERPINB2 as a reliable neuroendocrine toxic marker, with its expression significantly increased in both hypothalamus and pituitary gland cells following exposure to various types of toxins. Next, we introduced SERPINB2-fluorescence reporter system into loaded hypothalamic cells and pituitary gland cells within each chamber of the HP axis on a chip, respectively. By incorporating this SERPINB2 detection system into the loaded hypothalamic and pituitary gland cells within our chip platform, Our HP axis-on-chip platform can better mimic reciprocal neuroendocrine crosstalk between the hypothalamus and the pituitary gland in the brain microenvironments with improved efficiency in evaluating neuroendocrine toxicities of certain drug candidates.

Effects of lubricant-fuel mixing on particle emissions in a single cylinder direct injection spark ignition engine.

Gasoline direct injection (GDI) engines emit less carbon dioxide (CO2) than port fuel injection (PFI) engines when fossil fuel conditions are the same. However, GDI engines emit more ultrafine particulate matter, which can have negative health effects, leading to particulate emission regulations. To satisfy these regulations, various studies have been done to reduce particulate matter, and several studies focused on lubricants. This study focuses on the influence of lubricant on the formation of particulate matter and its effect on particulate emissions in GDI engines. An instrumented, combustion and optical singe-cylinder GDI engine fueled by four different lubricant-gasoline blends was used with various injection conditions. Combustion experiments were used to determine combustion characteristics, and gaseous emissions indicated that the lubricant did not influence mixture homogeneity but had an impact on unburned fuels. Optical experiments showed that the lubricant did not influence spray but did influence wall film formation during the injection period, which is a major factor affecting particulate matter generation. Particulate emissions indicated that lubricant included in the wall film significantly affected PN emissions depending on injection conditions. Additionally, the wall film influenced by the lubricant affected the overall particle size and its distribution.

Motility Improvement of Biomimetic Trachea Scaffold via Hybrid 3D-Bioprinting Technology.

A trachea has a structure capable of responding to various movements such as rotation of the neck and relaxation/contraction of the conduit due to the mucous membrane and cartilage tissue. However, current reported tubular implanting structures are difficult to impelement as replacements for original trachea movements. Therefore, in this study, we developed a new trachea implant with similar anatomical structure and mechanical properties to native tissue using 3D printing technology and evaluated its performance. A 250 µm-thick layer composed of polycaprolactone (PCL) nanofibers was fabricated on a rotating beam using electrospinning technology, and a scaffold with C-shaped cartilage grooves that mimics the human airway structure was printed to enable reconstruction of cartilage outside the airway. A cartilage type scaffold had a highest rotational angle (254°) among them and it showed up to 2.8 times compared to human average neck rotation angle. The cartilage type showed a maximum elongation of 8 times higher than that of the bellows type and it showed the elongation of 3 times higher than that of cylinder type. In cartilage type scaffold, gelatin hydrogel printed on the outside of the scaffold was remain 22.2% under the condition where no hydrogel was left in other type scaffolds. In addition, after 2 days of breathing test, the amount of gelatin remaining inside the scaffold was more than twice that of other scaffolds. This novel trachea scaffold with hydrogel inside and outside of the structure was well-preserved under external flow and is expected to be advantageous for soft tissue reconstruction of the trachea.

Development of a heat labile antibiotic eluting 3D printed scaffold for the treatment of osteomyelitis.

In general, osteomyelitis is treated with antibiotics, and in severe cases, the inflammatory bone tissue is removed and substituted with poly (methyl methacrylate) (PMMA) beads containing antibiotics. However, this treatment necessitates re-surgery to remove the inserted PMMA beads. Moreover, rifampicin, a primary heat-sensitive antibiotic used for osteomyelitis, is deemed unsuitable in this strategy. Three-dimensional (3D) printing technology has gained popularity, as it facilitates the production of a patient-customized implantable structure using various biodegradable biomaterials as well as controlling printing temperature. Therefore, in this study, we developed a rifampicin-loaded 3D scaffold for the treatment of osteomyelitis using 3D printing and polycaprolactone (PCL), a biodegradable polymer that can be printed at low temperatures. We successfully fabricated rifampicin-loaded PCL 3D scaffolds connected with all pores using computer-aided design and manufacturing (CAD/CAM) and printed them at a temperature of 60 °C to prevent the loss of the antibacterial activity of rifampicin. The growth inhibitory activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), the representative causative organisms of osteomyelitis, was confirmed. In addition, we optimized the rifampicin-loading capacity that causes no damage to the normal bone tissues in 3D scaffold with toxicity evaluation using human osteoblasts. The rifampicin-releasing 3D scaffold developed herein opens new possibilities of the patient-customized treatment of osteomyelitis.

Development of a flexible 3D printed scaffold with a cell-adhesive surface for artificial trachea.

Trachea stents are widely used to treat stenosis arising from various trachea injuries. However, they are associated with inflammation, re-stenosis, and tracheal obstruction. Seeking to overcome these problems, the development of an artificial trachea using tissue engineering has been explored. However, the artificial trachea did not mimic the natural rigidity and flexibility of the trachea and provide the micro-environment necessary for re-epithelialization. In this study, we developed a thermoplastic polyurethane (TPU) trachea scaffold that possesses a restoration characteristic, using flexible 3D printed patterns, and an improved cell attachment performance, utilizing electrospun fibers. With the aim of enhancing flexibility, we compared two geometric tubes, one with a straight pattern (SP) and the other with a wave pattern (WP). Simulation results showed that the WP scaffold was more flexible than the SP scaffold. A tensile expansion and torsion experiment demonstrated lower tensile strength and elastic modulus, and higher elongation ratio and rotation angle of the WP scaffold. Addition of the electrospun layers increased the tensile strength and elastic modulus and decreased the elongation ratio and rotation angle of both the SP and WP scaffolds. The same trend was observed regardless of electrospinning. However, polycaprolactone (PCL)-based scaffolds displayed lower elongation ratio and rotation angle in simulations and experiments. Although the cell attachment capacity of TPU-based electrospun WP scaffolds was less than 10% that of PCL-based scaffolds, the former showed good initial cell attachment performance and their cell numbers increased by more than three times within a week. The improved biomechanical performance and cell affinity of the TPU trachea scaffold could be exploited in patient-customized grafts for trachea reconstruction.