RESUMEN
Nano Zirconia (ZrO2) has been used in dental implants due to having excellent mechanical properties and biocompatibility that match the requirements for the purpose. Zirconia undergoes phase transformation during heating: monoclinic (room temperature to 1170 °C), tetragonal (1170 °C to 2370 °C), and cubic (>2370 °C). Most useful mechanical properties can be obtained when zirconia is in a multiphase form or in partially stabilized zirconia (PSZ), which is achieved by adding small amounts of a metal oxide dopant, such as MgO (magnesia). This study aimed to synthesize nano Mg-PSZ from a local resource found in West Kalimantan, Indonesia, and examine its structural stability, biochemical stability, and mechanical properties. Nano Mg-PSZ was prepared from a zircon local to Indonesia, from West Kalimantan Province, MgSO4â7H2O, and polyethylene glycol (PEG)-6000 was used as a template. The obtained t-ZrO2 after calcination at 800 °C was shown to be stable at room temperature. The highest percentage of the t-ZrO2 phase was obtained at Zr0.95Mg0.05O2 with a variation of 99.5%. The hardness of Mg-PSZ increased from 554 MPa for ZrO2 without MgO doping to 5266 MPa for ZrO2 with a doping of 10% MgO. An in vitro biodegradation test showed that the greater the concentration of MgO in doping the ZrO2, the greater the degradation resistance of Mg-PSZ in simulated body fluid (SBF) solution.
RESUMEN
Hydrogel-based wound dressings are often chosen for healing diabetic foot ulcers (DFU) in combination with herbal extracts. Moringa oleifera leaf (MOL) extract is a potent herb containing antimicrobial and anti-inflammatory bioactive substances. In this work, wound dressings based on polyvinyl alcohol (PVA), MOL extract, and graphene oxide (GO) were developed for DFU wound dressing. The PVA/MOL/GO hydrogel was synthesized using four cycles of a freeze-thaw process with varying concentrations of MOL extract. All hydrogels showed a water content of 83-88% and an equilibrium swelling ratio between 155-171%. After degradation in phosphate-buffered saline, the hydrogels showed a more open porous structure. We observed a degradation rate of 26-28%. Although the increase in MOL extract reduced the tensile strength of the hydrogel, the addition of GO increased the tensile strength. The PVA/MOL/GO hydrogel showed the highest antibacterial activity, with a reduction of 94% Gram-positive S. aureus and 82% Gram-negative E. coli. Finally, all samples possessed appropriate cytocompatibility with cell viability reaching 83-135% in 3T3L1 mouse fibroblast cells. This result was verified by in vitro wound-healing analysis performed by scratch assay. This study presents the potency of combined PVA, MOL, and GO as a biocompatible DFU wound dressing.
RESUMEN
Pancreatic ductal adenocarcinoma (PDAC), characterized with abundant tumor stroma, is a highly malignant tumor with poor prognosis. The tumor stroma largely consists of cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM), and is known to promote tumor growth and progression as well as acts as a barrier to chemotherapy. Inhibition of tumor stroma is highly crucial to induce the effect of chemotherapy. In this study, we delivered fibroblast growth factor 2 (FGF2) to human pancreatic stellate cells (hPSCs), the precursors of CAFs, using superparamagnetic iron oxide nanoparticles (SPIONs). FGF2 was covalently conjugated to functionalized PEGylated dextran-coated SPIONs. FGF2-SPIONs significantly reduced TGF-ß induced hPSCs differentiation (α-SMA and collagen-1 expression) by inhibiting pSmad2/3 signaling and inducing ERK1/2 activity, as shown with western blot analysis. Then, we established a stroma-rich self-assembling 3D heterospheroid model by co-culturing PANC-1 and hPSCs in 3D environment. We found that FGF2-SPIONs treatment alone inhibited the tumor stroma-induced spheroid growth. In addition, they also potentiated the effect of gemcitabine, as shown by measuring the spheroid size and ATP content. These effects were attributed to the reduced expression of the hPSC activation and differentiation marker, α-SMA. Furthermore, to demonstrate an application of SPIONs, we applied an external magnetic field to spheroids while incubated with FGF2-SPIONs. This resulted in an enhanced effect of gemcitabine in our 3D model. In conclusion, this study presents a novel approach to target FGF2 to tumor stroma using SPIONs and thereby enhancing the effect of gemcitabine as demonstrated in the complex 3D tumor spheroid model.
