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.

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.