In this paper, the synthesis and characterization of novel cisplatin-loaded collagen (COLL)/hydroxyapatite (HA) composite materials are presented. The composite materials were designed to obtain a COLL: HA weight ratio close to the bone composition. The content of embedded cisplatin was chosen to assure a concentration of cisplatin of 6 and 10 μM, respectively, into the culture media used in cell culture experiments. These cisplatin delivery systems were characterized by determining the physico-chemical properties of the composite material, the drug release process as well as their biological activity. Based on the in vitro data that showed the cytotoxic, anti-proliferative and anti-invasive activities of these multifunctional systems on G292 osteosarcoma cells in dependence on the cisplatin concentration released in culture medium, we conclude that the newly developed COLL/HA-cisplatin drug delivery system could be a feasible approach for locoregional chemotherapy of bone cancer.
The present study is supported by our previous findings suggesting that calcium fructoborate (CF) has anti-inflammatory and antioxidant properties. Thus, we investigated the effects of CF on a model for studying inflammatory disorders in vitro represented by lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells. This investigation was performed by analyzing the levels of some mediators released during the inflammatory process: cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukins IL-1beta and IL-6 as well as cyclooxygenase-2 (COX-2), the main enzyme responsible for endotoxin/LPS-induced prostaglandin synthesis by macrophages. We also measured production of nitric oxide (NO) that plays an important role in the cytotoxicity activity of macrophages towards microbial pathogens. After CF treatment of LPS-stimulated macrophages we found an up-regulation of TNF-alpha protein level in culture medium, no significant changes in the level of COX-2 protein expression and a decrease in NO production as well as in IL-1beta and IL-6 release. Collectively, this series of experiments indicate that CF affect macrophage production of inflammatory mediators. However, further research is required in order to establish whether CF treatment can be beneficial in suppression of pro-inflammatory cytokine production and against progression of endotoxin-related diseases.
The demand of calcium phosphate bioceramics for biomedical applications is constantly increasing. Efficient and cost-effective production can be achieved using naturally derived materials. In this work, calcium phosphate powders, obtained from dolomitic marble and Mytilus galloprovincialis seashells by a previously reported and improved Rathje method were used to fabricate microporous pellets through cold isostatic pressing followed by sintering at 1200 °C. The interaction of the developed materials with MC3T3-E1 pre-osteoblasts was explored in terms of cell adhesion, morphology, viability, proliferation, and differentiation to evaluate their potential for bone regeneration. Results showed appropriate cell adhesion and high viability without distinguishable differences in the morphological features. Likewise, the pre-osteoblast proliferation overtime on both naturally derived calcium phosphate materials showed a statistically significant increase comparable to that of commercial hydroxyapatite, used as reference material. Furthermore, evaluation of the intracellular alkaline phosphatase activity and collagen synthesis and deposition, used as markers of the osteogenic ability of these bioceramics, revealed that all samples promoted pre-osteoblast differentiation. However, a seashell-derived ceramic demonstrated a higher efficacy in inducing cell differentiation, almost equivalent to that of the commercial hydroxyapatite. Therefore, data obtained demonstrate that this naturally sourced calcium-phosphate material holds promise for applications in bone tissue regeneration.
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