Ketpat Vejjasilpa

Injectable oligomer-cross-linked chitosan hydrogels, designed to emulate the extracellular matrix (ECM) in tissue engineering, are conventionally formed through physical gelation.

A three-dimensional (3D) scaffold ideally provides hierarchical complexity and imitates the chemistry and mechanical properties of the natural cell environment. Here, we report on a stimuli-responsive photo-cross-linkable resin formulation for the fabrication of scaffolds by continuous digital light processing (cDLP), which allows for the mechano-stimulation of adherent cells. The resin comprises a network-forming trifunctional acrylate ester monomer (trimethylolpropane triacrylate, or TMPTA), N-isopropyl acrylamide (NiPAAm), cationic dimethylaminoethyl acrylate (DMAEA) for enhanced cell interaction, and 4-acryloyl morpholine (AMO) to adjust the phase transition temperature (T_trans) of the equilibrium swollen cross-polymerized scaffold. With glycofurol as a biocompatible solvent, controlled three-dimensional structures were fabricated and the transition temperatures were adjusted by resin composition. The effects of the thermally induced mechano-stimulation were investigated with mouse fibroblasts (L929) and myoblasts (C2C12) on printed constructs. Periodic changes in the culture temperature stimulated the myoblast proliferation.

The performance of dental resin-based composites (RBCs) heavily depends on the characteristic properties of the individual filler fraction. As specific information regarding the properties of the filler fraction is often missing, the current study aims to characterize the filler fractions of several contemporary computer-aided design/computer-aided manufacturing (CAD/CAM) RBCs from a material science point of view. The filler fractions of seven commercially available CAD/CAM RBCs featuring different translucency variants were analysed using Scanning Electron Microscopy (SEM) with Energy Dispersive X-ray Spectroscopy (EDS), Micro-X-ray Computed Tomography (µXCT), Thermogravimetric Analysis (TG) and X-ray Diffractometry (XRD). All CAD/CAM RBCs investigated included midifill hybrid type filler fractions, and the size of the individual particles was clearly larger than the individual specifications of the manufacturer. The fillers in Shofu Block HC featured a sphericity of ≈0.8, while it was <0.7 in all other RBCs. All RBCs featured only X-ray amorphous phases. However, in Lava Ultimate, zircon crystals with low crystallinity were detected. In some CAD/CAM RBCs, inhomogeneities (X-ray opaque fillers or pores) with a size <80 µm were identified, but the effects were minor in relation to the total volume (<0.01 vol.%). The characteristic parameters of the filler fraction in RBCs are essential for the interpretation of the individual material’s mechanical and optical properties.

Purpose SN-38, a potent chemotherapeutic drug, has not been used clinically because of its severe side effects and poor solubility. In this work, we aimed to evaluate the effect of dose and multiple injections of SN-38-loaded polymeric depots on antitumor efficacy and toxicity in vivo. Methods Preparation and characterization of SN-38-loaded depots were performed and evaluated in vitro using human glioblastoma cell line, U-87MG. Antitumor efficacy with different depot administrations including dose, position of depot injection and number of injections were evaluated in tumor model in nude mice. Results Depots encapsulated SN-38 with high encapsulation efficiency (~98.3%). High amount of SN-38 (3.0 ± 0.1 mg) was prolonged and controlled release over time and showed anticancer activity against U-87MG cell line in vitro. For one course administration, depots exhibited better antitumor efficacy and reduced toxicity compared to free SN-38. Elevated doses and multiple injections of SN-38-loaded depots and free SN-38 provided greater tumor growth inhibition and animal survival. All animals received SN-38-loaded depots were well tolerated and survived while most of those received free SN-38 died at day 30. Free SN-38 showed severe toxic effect compared to minimal toxicity from SN-38-loaded depots which was due to lower SN-38 level in systemic circulation. Fluorescence imaging and histopathology confirmed that SN-38 released from depots was detected throughout tumors 35 days post administration. Conclusions SN-38-loaded depots were proved as a promising new treatment for highly invasive glioblastoma multiforme with low acute toxicity due to controlled release of SN-38.

We investigate antitumor efficacy and 2D and 3D intratumoral distribution of 7-ethyl-10-hydroxycamptothecin (SN-38) from polymeric depots inside U-87MG xenograft tumor model in nude mice. Results showed that polymeric depots could be used to administer and controlled release of a large amount of SN-38 directly to the brain tumor model. SN-38 released from depots suppressed tumor growth, where the extent of suppression greatly depended on doses and the number of depot injections. Tumor suppression of SN-38 from depots was three-fold higher in animals which received double injections of depots at high dose (9.7 mg of SN-38) compared to single injection (2.2 mg). H&E staining of tumor sections showed that the area of tumor cell death/survival of the former group was two-fold higher than those of the latter group. Fluorescence imaging based on self-fluorescent property of SN-38 was used to evaluate the intratumoral distribution of this drug compared to histological results. The linear correlation between fluorescence intensity and the amount of SN-38 allowed quantitative determination of SN-38 in tumor tissues. Results clearly showed direct correlation between the amount of SN-38 in tumor sections and cancer cell death. Moreover, 3D reconstruction representing the distribution of SN-38 in tumors was obtained. Results from this study suggest the rationale for intratumoral drug administration and release of drugs inside tumor, which is necessary to design drug delivery systems with efficient antitumor activity.

One of the most useful techniques to treat cancer is chemotherapy. However, anticancer drugs, such as SN-38, have limited solubility with strong side effects. This work aims to use SN-38:β-cyclodextrin (β-CD) inclusion complex for an injectable polymeric in situ forming implant containing poly(ethylene glycol) (PEG), poly(ε-caprolactone), and poly(D, L-lactide). It was found that implant formation and SN-38 encapsulation efficiency directly depended on weight ratio of SN-38 and β-CD. At the ratio of SN-38:β-CD of 1:7, the implant could not be formed perfectly and had lower encapsulation efficiency. Reduction of the amount of β-CD to the ratio of 1:3 showed the higher encapsulation efficiency at 89.7 %. SN-38 release rate was also found to depend on β-CD content and the implant weight. In addition, their active form was protected when encapsulated inside implants.