In this study, polyvinyl alcohol (PVA) and gelatin based cryogels were prepared by crosslinking chemically or physically for tissue engineering applications. Different PVA/Gelatin ratios (100:0, 90:10, 70:30, 50:50) and crosslinking methods have been used to prepare cryogels; chemical and physical structure of the prepared matrices were analysed by FTIR and SEM; swelling and degradation profiles were followed. Chemical and physical crosslinking was obtained by using glutaraldehyde as crosslinker and by applying freeze thawing cycle, respectively. Gelatin concentration and crosslinking method had significant effect on the pore size, swelling ratio and degradation profiles of the cryogels. Biocompatibility of the cryogels were also investigated by MTT assay. SEM was used to investigate the cell morphology on the scaffolds. The MTT assay findings prove that physically crosslinked PVA/Gelatin scaffolds are more biocompatible and enhance more the adhesion and proliferation of mouse embryonic fibroblast cells (MEF) than chemically crosslinked PVA/Gelatin scaffolds. The overall results demonstrated that, the PVA/Gelatin cyrogels as a suitable biomaterial for tissue engineering applications and crosslinking methods affect the architecture and characteristic properties of the cryogels.
Glioblastoma (GBM, WHO grade IV) accounts for 50% of all the intracranial tumors and 70% of the primary malignant brain tumors. Although GBM often occurs in late adulthood (70% at a mean age of 53 years), up to 8.8% occur during childhood. Absence of specific symptoms is the predominant reason for which tumors are often detected at advanced stages, leading to poor prognosis with a mean survival of 1 year for GBM (18).
█ INTRODuCTIONA ny tumor that arises from the glial or supportive tissue of the brain or the spinal cord is called "glioma". One of the types of glioma is astrocytoma. Astrocytomas arise from astrocytes, the star-shaped cells, and are graded to describe their degree of abnormality. The most common grading system uses a scale of I to IV (15,16,18).AIm: Glioblastoma (GBM) is one of the lethal central nervous system tumors. One of the widely used chemical agents for the treatment of glioblastoma is temozolomide. It is an orally administered, deoxyribonucleic acid (DNA) alkylating agent. DNA alkylation triggers the death of tumor cells. However, some tumor cells are able to repair this type of DNA damage and thus lower the therapeutic effect of temozolomide. Laboratory and clinical studies indicate that temozolomide's anticancer effects might be strengthened when combined with other chemotherapeutic agents like etoposide or antioxidant agents like ascorbic acid. In this study, we aimed to evaluate the cytotoxic and oxidative stress effects of ascorbic acid (1000 µM), temozolomide (100 µM) and etoposide (25 µM) agents alone and in dual and triple combinations in a glioblastoma U87 MG cell culture.
mATERIAl and mEThODS:The cytotoxic and oxidative stress effects were investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis methods.
RESulTS:Cytotoxicity tests showed that etoposide, temozolomide, "etoposide+ascorbic acid", "temozolomide+ascorbic acid", "temozolomide+etoposide" and "temozolomide+etoposide+ascorbic acid" combinations have anti-proliferative effects. The maximum anti-proliferation response was observed in the "temozolomide+etoposide+ascorbic acid"-added group. Similarly LC-MS/MS analyses showed that minimum oxidative DNA damage occurred in the "temozolomide+etoposide+ascorbic acid"-added group.CONCluSION: Ascorbic acid decreases the cytotoxic and genotoxic effect of etoposide and etoposide-temozolomide combination but it has no meaningful effect on temozolomide's toxicity.
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