Kaempferol mitigates sepsis-induced acute lung injury by modulating the SphK1/S1P/S1PR1/MLC2 signaling pathway to restore the integrity of the pulmonary endothelial cell barrier.

Sepsis-induced acute lung injury (SALI) is the common complication of sepsis, resulting in high incidence and mortality rates. The primary pathogenesis of SALI is the interplay between acute inflammation and endothelial barrier damage. Studies have shown that kaempferol (KPF) has anti-sepsis properties. Sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P) signaling pathway's significance in acute lung damage and S1P receptor 1 (S1PR1) agonists potential in myosin light chain 2 (MLC2) phosphorylation are documented. Whether KPF can regulate the SphK1/S1P/S1PR1/MLC2 signaling pathway to protect the lung endothelial barrier remains unclear. This study investigates the KPF's therapeutic effects and molecular mechanisms in repairing endothelial cell barrier damage in both LPS-induced sepsis mice and human umbilical vein endothelial cells (HUVECs). KPF significantly reduced lung tissue damage and showed anti-inflammatory effects by decreasing IL-6 and TNF-α synthesis in the sepsis mice model. Further, KPF administration can reduce the high permeability of the LPS-induced endothelial cell barrier and alleviate lung endothelial cell barrier injury. Mechanistic studies showed that KPF pretreatment can suppress MLC2 hyperphosphorylation and decrease SphK1, S1P, and S1PR1 levels. The SphK1/S1P/S1PR1/MLC2 signaling pathway controls the downstream proteins linked to endothelial barrier damage, and the Western blot (WB) showed that KPF raised the protein levels. These proteins include zonula occludens (ZO)-1, vascular endothelial (VE)-cadherin and Occludin. The present work revealed that in mice exhibiting sepsis triggered by LPS, KPF strengthened the endothelial barrier and reduced the inflammatory response. The SphK1/S1P/S1PR1/MLC2 pathway's modulation is the mechanism underlying this impact.

3D Foaming Printing Biomimetic Hierarchically Macro-Micronanoporous Hydrogels for Enhancing Cell Growth and Proliferation.

Hydrogel, recognized as a promising biomaterial for tissue engineering, possesses notable characteristics, including high water uptake, an interconnected porous structure, and excellent permeability. However, the intricate task of fabricating a hierarchically macro-micronanoporous structure, essential for providing adequate space for nutrient diffusion and cell growth within hydrogels, remains a formidable challenge. In response to these challenges, this study introduces a sustainable and straightforward three-dimensional (3D) foaming printing strategy to produce hierarchically macro-micronanoporous hydrogels (HPHs) without the utilization of porogens and post-etching process. This method entails the controlled generation of air bubbles within the hydrogels through the application of optimal mechanical stirring rates. Subsequent ultraviolet (UV) cross-linking serves to effectively stabilize the macropores within the HPHs. The resulting hierarchically macro-micronanoporous structures demonstrate a substantial improvement in the viability, adhesion, and proliferation of human umbilical vein endothelial cells (HUVECs) when incubated with the hydrogels. These findings present a significant advancement in the fabrication of hierarchically macro-micronanoporous hydrogels, with potential applications in the fields of tissue engineering and organoid development.

Projection Stereolithography 3D-Printed Bio-Polymer with Thermal Assistance.

A stereolithography process with thermal assistance is proposed in this work to address the tradeoff between the flowability and the high concentration of solute loadings at room temperature, through which the improved performance of polymers prepared using stereolithography 3D printing can be achieved. For the experiment, polyethylene glycol diacrylate (PEGDA) with a high molecular weight of 4000 is adopted to improve the mechanical properties of 2-Hydroxyethyl methacrylate (HEMA). For the polymer of HEMA, the highest soluble concentration of PEGDA is about 20 wt% at 25 °C (room temperature) while the concentration could be raised up to 40 wt% as the temperature increases to 60 °C. The 3D printing tests showed that the objects could be easily fabricated with the HEMA polymer loaded with 40 wt% of PEGDA through the thermally assisted projection stereolithography technology. By adding the 40 wt% of PEGDA, the Young's modulus has been enhanced by nearly 390% compared to the HEMA resin without solute, of which the Young's modulus is 63.31 ± 2.72 MPa. The results of the cell proliferation test proved that the HEMA resin loaded with PEGDA led to a better biocompatibility compared to the HEMA resin without the loading of the PEGDA solute. All of the results demonstrate that the polymer loaded with high solute is feasible to be precisely 3D-printed using the projection stereolithography process with thermal assistance, and the improved mechanical properties are beneficial for biomedical applications.