Effects of 2,3-Dehydrosilybin and Its Galloyl Ester and Methyl Ether Derivatives on Human Umbilical Vein Endothelial Cells.

The effects in vitro of 2,3-dehydrosilybin and several galloyl esters and methyl ethers on the viability, proliferation, and migration of human umbilical vein endothelial cells (HUVECs) were evaluated. The monogalloyl esters were synthesized by a chemoselective esterification method or by Steglich esterification of suitably protected 2,3-dehydrosilybin (1) with protected gallic acid. 2,3-Dehydrosilybin (1) displayed more potent cytotoxic, antiproliferative, and antimigratory activities (IC50 12.0, 5.4, and 12.2 µM, respectively) than silybin. The methylated derivatives were less active, with the least potent being 3,7-di-O-methyl-2,3-dehydrosilybin (6). On the other hand, galloylation at C-7 OH and C-23 OH markedly increased the cytotoxicity and the effects on the proliferation and migration of HUVECs. The most active derivative was 7-O-galloyl-2,3-dehydrosilybin (13; IC50 value of 3.4, 1.6, and 4.7 µM in the cytotoxicity, inhibition of proliferation, and antimigratory assays, respectively). Overall, this preliminary structure-activity relationship study demonstrated the importance of a 2,3-double bond, a C-7 OH group, and a galloyl moiety in enhancing the activity of flavonolignans toward HUVECs.

Effects of silver nanoparticles on primary cell cultures of fibroblasts and keratinocytes in a wound-healing model.

BACKGROUND: Nanoparticles are widely used in different technological fields, one of which is medicine. Because of their antibacterial properties, silver nanoparticles (AgNPs) are used in several types of wound dressings for the treatment of burns and nonhealing wounds, but their influence on each component of the wound-healing process remains unclear. In the present study, we evaluated the effects of AgNPs on normal human dermal fibroblasts (NHDFs) and normal human epidermal keratinocytes (NHEKs). Both cell types are important for wound healing, including with regard to inflammation, proliferation and tissue remodeling. Each phase of wound healing can be characterized by the secretion of cytokines, chemokines and growth factors. METHODS: The production of inflammatory parameters (tumor necrosis factor α [TNF-α], interleukin-6 [IL-6], IL-8 and IL-12 and cyclooxygenase-2 [COX-2]), angiogenesis parameters (vascular endothelial growth factor [VEGF], granulocyte macrophage colony-stimulating factor) and matrix metalloproteinases (MMP-1, MMP-2, MMP-3 and MMP-9) by NHDFs and NHEKs were examined by ELISA or Western blot after 24 and 48 hours of incubation with AgNPs. RESULTS: We found that AgNPs decreased some inflammatory cytokines (TNF-α and IL-12) and growth factors (VEGF) that were produced by NHDFs and NHEKs after 24 and 48 hours and decreased the expression of COX-2 after 24 hours but only at the highest concentration of AgNPs (25 parts per million). CONCLUSIONS: The results indicate that NHEKs are more susceptible to the application of AgNPs than NHDFs, and AgNPs may be useful for medical applications for the treatment of wounds.

In Vitro AuNPs' Cytotoxicity and Their Effect on Wound Healing.

Recently, due to their unique properties, gold nanoparticles (AuNPs) have been used in many biological applications. However, little is known about their toxicity when they come into contact with a biological system. Based on the proposal that AuNPs can have a positive effect on wound healing, the present study investigated the influence of negatively-charged-surface AuNPs (average diameter 25-50 nm) on the viability of normal human dermal fibroblasts (NHDF) and normal human epidermal keratinocytes (NHEK). Moreover, we evaluated the effect of AuNPs on the secretion of proteins involved in wound healing, such as interleukin-8 and - 12 (IL-8, IL-12), tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), basic fibroblast grow factor (bFGF), and granulocyte-macrophage colony-stimulating factor (GM-CSF). The results showed that AuNPs were not toxic to NHDF and NHEK. They showed a decrease in AuNPs' production of pro-inflammatory cytokines IL-6, IL-12 and TNF-α, as well as proteins involved in angiogenesis such as VEGF and bFGF. Thus, we suggest that AuNPs could have anti-inflammatory and anti-angiogenic activity.

The response of osteoblast-like SaOS-2 cells to modified titanium surfaces.

PURPOSE: To study the effects of different chemically modified titanium surfaces on the proliferation, differentiation, adhesion, and apoptosis of osteoblast-like SaOS-2 cells. MATERIALS AND METHODS: In this work, six different titanium materials were tested and compared to each other: (1) glazed; (2) unglazed; (3) unglazed and alkali-etched; (4) unglazed, sandblasted, acid- and alkali-etched; (5) unglazed and coated with zirconium nitride; and (6) unglazed, sandblasted, and acid-etched. The production of alkaline phosphatase (ALP), tumor necrosis factor alpha (TNF-α), matrix metalloproteinase-2, and the expression of adhesion proteins (integrin α3ß1, vinculin) were evaluated using ELISA. Finally, the apoptosis of cells was analyzed by flow cytometry. RESULTS: The most significant differences were found for unglazed sandblasted acid- and alkali-etched titanium discs compared with unglazed titanium discs. The production of TNF-α was decreased after 24 hours, as was the production of ALP after 72 hours. In contrast, the expression of integrin α3ß1 was increased after 6 hours. None of the titanium discs showed an apoptotic effect on cells. CONCLUSIONS: This study has shown that physical surface treatments (such as surface roughness) play a more important role than chemical modifications. Generally, chemical modifications such as acid- and alkali-etching can affect the wettability of titanium surfaces, making a surface hydrophilic or hydrophobic according to the modification. The cell attachment is better on hydrophilic surfaces, while hydrophilic surfaces may slightly decrease the expression of ALP activity.

Comparing biocompatibility of gingival fibroblasts and bacterial strains on a different modified titanium discs.

The modification of implant surface situated in the area of peri-implant sulcus has important role in bacterial and cell adhesion. Six different chemically and physically modified titanium discs were prepared: glazed (Tis-MALP), unglazed (Tis-O), unglazed and alkali-etched (Tis-OA), unglazed and coated with ZrN (Tis-OZ), unglazed, sand blasted, and acid etched (Tis-OPAE), and unglazed, sand blasted, acid, and alkali etched (Tis-OPAAE). Analysis of surface topography was determined using scanning electron microscopy and atomic force microscopy (AFM). Biocompatibility of gingival fibroblasts was characterized by the production of tumor necrosis factor alpha, collagen I, matrix metalloproteinase 2 (MMP-2) after 24 and 72 h and expression of α3 ß1 integrin and vinculin using enzyme-linked immunosorbent assay (ELISA) or modified ELISA after 6 and 24 h. Microorganism adhesion (five bacterial strains) and biofilm formation was also evaluated. The adhesion of bacteria and gingival fibroblasts was significantly higher on titanium disc Tis-OPAAE and biofilm formation on the same surface for Streptococcus mutans, Streptococcus gordonii, and Streptococcus intermedius. The gingival fibroblasts on Tis-OPAAE disc had also significantly lower production of MMP-2. The collagen production was significantly lower on all surfaces with roughness higher than 0.2 µm. This study confirmed that the titanium disc with the surface roughness 3.39 µm (Tis-OPAAE) supported the adhesion of bacterial strains as well as gingival fibroblasts.

Osteoblast and gingival fibroblast markers in dental implant studies.

BACKGROUND: Dental implants are a suitable option for the replacement of some or all missing teeth. Their main function is to secure the stability of the artificial tooth. The implant material interacts with several cell types including osteoblasts, gingival fibroblasts, periodontal ligament fibroblasts and monocytes. The most common material used is pure titanium which is corrosion resistant and has an elasticity modulus similar to that of bone. In recent years, diverse modified titanium surfaces have also been developed. The wound healing around the implant is a complex process that determines how well the host can heal and accept the implanted material. For this reason, search for markers of the biocompatibility of these new materials is paramount. To identify markers found to be suitable for studying the biocompatibility of dental implants. METHODS: Review of Pubmed and Web of Science databases for the years 1958-2010. CONCLUSIONS: The surface of dental implant material should enhance firm attachment of the implant to junctional epithelium, soft connective tissue and bone. For the purposes of dental implant biocompatibility studies, a number of markers produced by osteoblasts or by cells of periodontal ligament have been proposed. In general, the most typical markers for osteoblasts and fibroblasts are alkaline phosphatase and collagen I, respectively. The involvement of both cell types in the inflammatory response is primarily evaluated by determination of tumour necrosis factor α and proinflammatory interleukins.