We examined the immunomodulatory and anti-inflammatory effects of asiatic acid (AA) in atopic dermatitis (AD). AA treatment (5–20 µg/mL) dose-dependently suppressed the tumor necrosis factor (TNF)-α level and interleukin (IL)-6 protein expression in interferon (IFN)-γ + TNF-α-treated HaCaT cells. The 2,4-dinitrocholrlbenzene (DNCB)-induced AD animal model was developed by administering two AA concentrations (30 and 75 mg/kg/d: AD + AA-L and AD + AA-H groups, respectively) for 18 days. Interestingly, AA treatment decreased AD skin lesions formation and affected other AD characteristics, such as increased ear thickness, lymph node and spleen size, dermal and epidermal thickness, collagen deposition, and mast cell infiltration in dorsal skin. In addition, in the DNCB-induced AD animal model, AA treatment downregulated the mRNA expression level of AD-related cytokines, such as Th1- (TNF-α and IL-1β and -12) and Th2 (IL-4, -5, -6, -13, and -31)-related cytokines as well as that of cyclooxygenase-2 and CXCL9. Moreover, in the AA treatment group, the protein level of inflammatory cytokines, including COX-2, IL-6, TNF-α, and IL-8, as well as the NF-κB and MAPK signaling pathways, were decreased. Overall, our study confirmed that AA administration inhibited AD skin lesion formation via enhancing immunomodulation and inhibiting inflammation. Thus, AA can be used as palliative medication for regulating AD symptoms.

In this study, we fabricated a three-dimensional (3D) scaffold using industrial polylactic acid (PLA), which promoted the proliferation and differentiation of human neural stem cells. An industrial PLA 3D scaffold (IPTS) cell chip with a square-shaped pattern was fabricated via computer-aided design and printed using a fused deposition modeling technique. To improve cell adhesion and cell differentiation, we coated the IPTS cell chip with gold nanoparticles (Au-NPs), nerve growth factor (NGF) protein, an NGF peptide fragment, and sonic hedgehog (SHH) protein. The proliferation of F3.Olig2 neural stem cells was increased in the IPTS cell chips coated with Au-NPs and NGF peptide fragments when compared with that of the cells cultured on non-coated IPTS cell chips. Cells cultured on the IPTS-SHH cell chip also showed high expression of motor neuron cell-specific markers, such as HB9 and TUJ-1. Therefore, we suggest that the newly engineered industrial PLA scaffold is an innovative tool for cell proliferation and motor neuron differentiation.

Biocompatibility is very important for cell growth using 3D printers, but biocompatibility materials are very expensive. In this study, we investigated the possibility of cell culture by the surface modification of relatively low-cost industrial materials and an efficient three-dimensional (3D) scaffold made with an industrial ABS filament for cell proliferation, spheroid formation, and drug screening applications. We evaluated the adequate structure among two-layer square shape 3D scaffolds printed by fused deposition modeling with variable infill densities (10–50%). Based on the effects of these scaffolds on cell proliferation and spheroid formation, we conducted experiments using the industrial ABS 3D scaffold (IA3D) with 40% of infill density, which presented an external dimension of (XYZ) 7650 µm × 7647 µm × 210 µm, 29.8% porosity, and 225 homogenous micropores (251.6 µm × 245.9 µm × 210 µm). In the IA3D, spheroids of cancer HepG2 cells and keratinocytes HaCaT cells appeared after 2 and 3 days of culture, respectively, whereas no spheroids were formed in 2D culture. A gold nanoparticle-coated industrial ABS 3D scaffold (GIA3D) exhibited enhanced biocompatible properties including increased spheroid formation by HepG2 cells compared to IA3D (1.3-fold) and 2D (38-fold) cultures. Furthermore, the cancer cells exhibited increased resistance to drug treatments in GIA3D, with cell viabilities of 122.9% in industrial GIA3D, 40.2% in IA3D, and 55.2% in 2D cultures when treated with 100 µM of mitoxantrone. Our results show that the newly engineered IA3D is an innovative 3D scaffold with upgraded properties for cell proliferation, spheroid formation, and drug-screening applications.

We developed a multi-channel cell chip containing a three-dimensional (3D) scaffold for horizontal co-culture and drug toxicity screening in multi-organ culture (human glioblastoma, cervical cancer, normal liver cells, and normal lung cells). The polydimethylsiloxane (PDMS) multi-channel cell chip (PMCCC) was based on fused deposition modeling (FDM) technology. The architecture of the PMCCC was an open-type cell chip and did not require a pump or syringe. We investigated cell proliferation and cytotoxicity by conducting 3-(4,5-dimethylthiazol-2-yl)-2,5-dphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays and analysis of oleanolic acid (OA)-treated multi-channel cell chips. The results of the MTT and LDH assays showed that OA treatment in the multi-channel cell chip of four cell lines enhanced chemoresistance of cells compared with that in the 2D culture. Furthermore, we demonstrated the feasibility of the application of our multi-channel cell chip in various analysis methods through Annexin V-fluorescein isothiocyanate/propidium iodide staining, which is not used for conventional cell chips. Taken together, the results demonstrated that the PMCCC may be used as a new 3D platform because it enables simultaneous drug screening in multiple cells by single point injection and allows analysis of various biological processes.

Prostate cancer is one of the most preventable cancers, yet effective therapeutics, especially targeted therapy, are still lacking. Saponin has been reported to possess various biological properties such as anti-cancer and anti-inflammatory activity. In this study, the anti-tumor activity of magnetic nanoparticles loaded with ethylene glycol and a saponin complex (ESMP) against DU145 prostate cancer cells was examined. Composite nanoparticles with an average size of 23 nm were prepared using a chemical co-precipitation technique. The ESMP were cytotoxic to DU145 cells and specifically inhibited cell proliferation. In contrast, the magnetic nanoparticles by themselves showed no significant cytotoxicity. The expression levels of the angiogenesis related proteins, including phospho-extracellular signal-regulated kinase, p38 and pAKT, decreased after ESMP treatment. This study highlights the therapeutic potential of using ESMP for targeted-therapy against prostate cancer.

A novel, three-dimensional (3D) skin cell chip was developed using a three-floor structure and a nanogold platform structure cell chip for the ex vivo 3D cell growth simulation of skin cells and to evaluate the efficacy of the system for detection of cosmetic drugs. The nanogold platform structures were fabricated through a nanoporous alumina mask, and the structural formations were confirmed via scanning electron microscopy. A three-floor structure cell chip was fabricated using a two-photon stereolithography process. The skin cells were attached to RGD (Arg-Gly-Asp) peptide nanopatterned surfaces, and electrochemical tools were applied to the skin cells attached to the chip surface. Treatment with imidazolidinyl urea induced a loss of cell viability in a concentration-dependent manner using the three-floor structure cell chip and nanogold structured cell chip. The observed increased chemoresistance to cosmetic drugs in the three-floor structure cell chip might result from the effects of cell confluence. Furthermore, these results strongly indicate that this new cell array system is suitable for high-throughput cytotoxicity and genotoxicity screening applications.