Tissue transglutaminase (TG2) is a member of the transglutaminase family that catalyzes Ca2+-depe... more Tissue transglutaminase (TG2) is a member of the transglutaminase family that catalyzes Ca2+-dependent protein crosslinks and hydrolyzes guanosine 5′-triphosphate (GTP). The conformation and functions of TG2 are regulated by Ca2+ and GTP levels; the TG2 enzymatically active open conformation is modulated by high Ca2+ concentrations, while high intracellular GTP promotes the closed conformation, with inhibition of the TG-ase activity. TG2’s unique characteristics and its ubiquitous distribution in the intracellular compartment, coupled with its secretion in the extracellular matrix, contribute to modulate the functions of the protein. Its aberrant expression has been observed in several cancer types where it was linked to metastatic progression, resistance to chemotherapy, stemness, and worse clinical outcomes. The N-terminal domain of TG2 binds to the 42 kDa gelatin-binding domain of fibronectin with high affinity, facilitating the formation of a complex with β-integrins, essential ...
Abstract During the last decade, graphene family nanomaterials (GFNs) have proven unique physicoc... more Abstract During the last decade, graphene family nanomaterials (GFNs) have proven unique physicochemical properties, with several applications being continuously explored. Among them, recent advances in nanomedicine revealed extensive interest for fabricating graphene-based cell-instructive environments for drug/gene delivery and cancer therapy, engineering stem cell responses, bacteria-killing and tissue engineering platforms, biosensing and cellular imaging. However, the full merging of GFN with bio-nanotechnology is still in its infancy, with many challenges remaining unexplored. The purpose of this chapter is to introduce a critical overview of the latest advances achieved in the synthesis and functionalization of graphene and its derivates for nanomedicine, as well as prospective expansion of this fascinating research field.
Due to their excellent mechanical and biocompatibility properties, titanium-based implants are su... more Due to their excellent mechanical and biocompatibility properties, titanium-based implants are successfully used as biomedical devices. However, when new bone formation fails for different reasons, impaired fracture healing becomes a clinical problem and affects the patient's quality of life. We aimed to design a new bioactive surface of titanium implants with a synergetic PEG biopolymer-based composition for gradual delivery of growth factors (FGF2, VEGF, and BMP4) during bone healing. The optimal architecture of non-cytotoxic polymeric coatings deposited by dip coating under controlled parameters was assessed both in cultured cells and in a rat tibial defect model (100% viability). Notably, the titanium adsorbed polymer matrix induced an improved healing process when compared with the individual action of each biomolecules. High-performance mass spectrometry analysis demonstrated that recovery after a traumatic event is governed by specific differentially regulated proteins, a...
Osseous implantology’s material requirements include a lack of potential for inducing allergic di... more Osseous implantology’s material requirements include a lack of potential for inducing allergic disorders and providing both functional and esthetic features for the patient’s benefit. Despite being bioinert, Zirconia ceramics have become a candidate of interest to be used as an alternative to titanium dental and cochlear bone-anchored hearing aid (BAHA) implants, implying the need for endowing the surface with biologically instructive properties by changing basic parameters such as surface texture. Within this context, we propose anisotropic and isotropic patterns (linear microgroove arrays, and superimposed crossline microgroove arrays, respectively) textured in zirconia substrates, as bioinstructive interfaces to guide the cytoskeletal organization of human mesenchymal stem cells (hMSCs). The designed textured micro-nano interfaces with either steep ridges and microgratings or curved edges, and nanoroughened walls obtained by direct femtosecond laser texturing are used to evaluate...
The modification of implant devices with biocompatible coatings has become necessary as a consequ... more The modification of implant devices with biocompatible coatings has become necessary as a consequence of premature loosening of prosthesis. This is caused mainly by chronic inflammation or allergies that are triggered by implant wear, production of abrasion particles, and/or release of metallic ions from the implantable device surface. Specific to the implant tissue destination, it could require coatings with specific features in order to provide optimal osseointegration. Pulsed laser deposition (PLD) became a well-known physical vapor deposition technology that has been successfully applied to a large variety of biocompatible inorganic coatings for biomedical prosthetic applications. Matrix assisted pulsed laser evaporation (MAPLE) is a PLD-derived technology used for depositions of thin organic material coatings. In an attempt to surpass solvent related difficulties, when different solvents are used for blending various organic materials, combinatorial MAPLE was proposed to grow t...
Here we describe a small-molecule inhibitor (SMI) that disrupts the tissue transglutaminase 2 (TG... more Here we describe a small-molecule inhibitor (SMI) that disrupts the tissue transglutaminase 2 (TG2)-fibronectin (FN) interaction. TG2 is a multifunctional protein, with enzymatic (transglutaminase, isopeptidase, protein disulfide isomerase), GTPase, and extracellular matrix (ECM) scaffold activities. TG2 directly interacts with FN through its N-terminus domain, playing an important role in stabilizing ternary TG2/FN/integrin complexes, which regulate cell adhesion to the matrix. Our group has previously shown that TG2 overexpressed in ovarian cancer (OC) promotes epithelial-to-mesenchymal transition (EMT) contributing to OC cell invasiveness and metastatic behavior. We showed that the interaction with FN is critical to these functions. Proximity ligation assay was used to measure TG2/integrin beta 1 interaction in OC tumors and identified TG2/integrin beta 1 complex in >50% of ovarian tumors, irrespective of histologic type. Based on those findings, we conducted the high-throughp...
Increasing evidence correlates the metastatic progression and post-chemotherapy recurrence of ova... more Increasing evidence correlates the metastatic progression and post-chemotherapy recurrence of ovarian cancer (OC) to a small population of cancer stem cells (CSCs), resistant to traditional chemotherapy and responsible for tumor relapse. Tissue transglutaminase (TG2) is a multifunctional protein, with enzymatic and scaffold functions, overexpressed in ovarian carcinomas, where it promotes metastasis. Independently of its enzymatic function, TG2 can be secreted in the extracellular compartment where it increases cell adhesion to the fibronectin (FN) matrix by regulating integrins clustering and matrix reorganization. We hypothesized that by binding to the integrins and FN, TG2 promotes survival of CSCs and supports OC spheroid formation. Our data demonstrate that TG2, β1 integrin, and FN1 expression are markedly increased in OC spheroids compared with monolayers and are enriched in successive sphere generations. Immunofluorescence (IF) staining supports that TG2 forms abundant comple...
Our study focused on the long-term degradation under simulated conditions of coatings based on di... more Our study focused on the long-term degradation under simulated conditions of coatings based on different compositions of polycaprolactone-polyethylene glycol blends (PCL-blend-PEG), fabricated for titanium implants by a dip-coating technique. The degradation behavior of polymeric coatings was evaluated by polymer mass loss measurements of the PCL-blend-PEG during immersion in SBF up to 16 weeks and correlated with those yielded from electrochemical experiments. The results are thoroughly supported by extensive compositional and surface analyses (FTIR, GIXRD, SEM, and wettability investigations). We found that the degradation behavior of PCL-blend-PEG coatings is governed by the properties of the main polymer constituents: the PEG solubilizes fast, immediately after the immersion, while the PCL degrades slowly over the whole period of time. Furthermore, the results evidence that the alteration of blend coatings is strongly enhanced by the increase in PEG content. The biological asses...
The ability of commercial monolayer graphene oxide (GO) and graphene oxide nanocolloids (GOC) to ... more The ability of commercial monolayer graphene oxide (GO) and graphene oxide nanocolloids (GOC) to interact with different unicellular systems and biomolecules was studied by analyzing the response of human alveolar carcinoma epithelial cells, the yeast Saccharomyces cerevisiae and the bacteria Vibrio fischeri to the presence of different nanoparticle concentrations, and by studying the binding affinity of different microbial enzymes, like the α-l-rhamnosidase enzyme RhaB1 from the bacteria Lactobacillus plantarum and the AbG β-d-glucosidase from Agrobacterium sp. (strain ATCC 21400). An analysis of cytotoxicity on human epithelial cell line A549, S. cerevisiae (colony forming units, ROS induction, genotoxicity) and V. fischeri (luminescence inhibition) cells determined the potential of both nanoparticle types to damage the selected unicellular systems. Also, the protein binding affinity of the graphene derivatives at different oxidation levels was analyzed. The reported results highl...
Eyes absent (EYA) are non-thiol-based protein tyrosine phosphatases (PTPs) that also have transcr... more Eyes absent (EYA) are non-thiol-based protein tyrosine phosphatases (PTPs) that also have transcriptional co-activator functions. Their PTP activity is involved in various pathologies. Recently, we demonstrated that Src tyrosine kinase phosphorylates human EYA3 by controlling its subcellular localization. We also found EYA3′s ability to autodephosphorylate, while raising the question if the two opposing processes could be involved in maintaining a physiologically adequate level of phosphorylation. Using native and bottom-up mass spectrometry, we performed detailed mapping and characterization of human EYA3 Src-phosphorylation sites. Thirteen tyrosine residues with different phosphorylation and autodephosphorylation kinetics were detected. Among these, Y77, 96, 237, and 508 displayed an increased resistance to autodephosphorylation. Y77 and Y96 were found to have the highest impact on the overall EYA3 phosphorylation. Using cell cycle analysis, we showed that Y77, Y96, and Y237 are i...
The potential of mesenchymal stem cells (MSCs) for implantology and cell-based therapy represents... more The potential of mesenchymal stem cells (MSCs) for implantology and cell-based therapy represents one of the major ongoing research subjects within the last decades. In bone regeneration applications, the various environmental factors including bioactive compounds such as growth factors, chemicals and physical characteristics of biointerfaces are the key factors in controlling and regulating osteogenic differentiation from MSCs. In our study, we have investigated the influence of Lactoferrin (Lf) and Hydroxyapatite (HA) embedded within a biodegradable PEG-PCL copolymer on the osteogenic fate of MSCs, previous studies revealing an anti-inflammatory potential of the coating and osteogenic differentiation of murine pre-osteoblast cells. The copolymer matrix was obtained by the Matrix Assisted Pulsed Laser Evaporation technique (MAPLE) and the composite layers containing the bioactive compounds (Lf, HA, and Lf-HA) were characterised by Scanning Electron Microscopy and Atomic Force Micro...
Cancer⁻stroma interactions play a key role in cancer progression and response to standard chemoth... more Cancer⁻stroma interactions play a key role in cancer progression and response to standard chemotherapy. Here, we provide a summary of the mechanisms by which the major cellular components of the ovarian cancer (OC) tumor microenvironment (TME) including cancer-associated fibroblasts (CAFs), myeloid, immune, endothelial, and mesothelial cells potentiate cancer progression. High-grade serous ovarian cancer (HGSOC) is characterized by a pro-inflammatory and angiogenic signature. This profile is correlated with clinical outcomes and can be a target for therapy. Accumulation of malignant ascites in the peritoneal cavity allows for secreted factors to fuel paracrine and autocrine circuits that augment cancer cell proliferation and invasiveness. Adhesion of cancer cells to the mesothelial matrix promotes peritoneal tumor dissemination and represents another attractive target to prevent metastasis. The immunosuppressed tumor milieu of HGSOC is permissive for tumor growth and can be modulate...
Abstract In this study, coatings based on lysozyme embedded into a matrix of polyethylene glycol ... more Abstract In this study, coatings based on lysozyme embedded into a matrix of polyethylene glycol (PEG) and polycaprolactone (PCL) were fabricated by two different methods (Matrix Assisted Pulsed Laser Evaporation – MAPLE and Dip Coating) for obtaining antimicrobial coatings envisaged for long term medical applications. Coatings with different PEG:PCL compositions (3:1; 1:1; 1:3) were synthesized in order to evaluate the antimicrobial activity of lysozyme embedded into the polymeric matrix. The main surface features, such as roughness and wettability, with impact on the microbial adhesion as well as on the eukaryote cell function were measured. The obtained composite coatings exhibited a significant antibacterial activity against Escherichia coli, Bacillus subtilis, Enterococcus faecalis and Staphylococcus aureus strains. As well, specific blended coatings showed appropriate viability, good spreading and normal cell morphology of SaOs2 human osteoblasts and mesenchymal stem cells (MSCs). These investigations highlight the suitability of biodegradable composites as implant coatings for decreasing the risk of bacterial contamination associated with prosthetic procedures.
The bipotent nature of the HepaRG cell line is a unique property among human hepatoma-derived cel... more The bipotent nature of the HepaRG cell line is a unique property among human hepatoma-derived cells. Cell treatment with specific differentiation inducers results in a mixture of hepatocyte- and biliary-like cells, accompanied by upregulation of liver-specific proteins, drug metabolizing enzymes, transcription regulators, membrane receptors or innate immune response effectors. These features make the HepaRG cells a suitable and handy replacement for primary hepatocytes, to study hepatic functions in vitro. However, cell differentiation is a long, variable process, requiring special culture conditions, while the resulting mixed cell populations is usually a major drawback. This process can potentially be controlled by interface characteristics, such as substrate topography. To screen for such novel substrates, we have first developed a new HepaRG cell line, designated as HepaRGDsRed, expressing the reporter gene DsRed. The fluorescent protein was expressed in hepatocyte- and not biliary-like cells, in a differentiation dependent-manner. We have further used replicated microstructured gradients of polydimethylsiloxane (PDMS) that allow three-dimensional manipulation in vitro, to monitor HepaRGDsRed differentiation in real time. We demonstrate that this approach enables the controlled assembly of viable hepatocyte-like cells for functional studies, which can be maintained in culture without loss of differentiation. The regulated expression of the DsRed reporter proved a valuable tool not only for rapid screening of novel cell growth substrates favoring cell differentiation, but also, to enrich the hepatocyte-like cell population by fluorescence-activated cell sorting to investigate liver-specific processes in vitro.
Two Photon Polymerization of Ormosils. [AIP Conference Proceedings 1278, 843 (2010)]. A. Matei, M... more Two Photon Polymerization of Ormosils. [AIP Conference Proceedings 1278, 843 (2010)]. A. Matei, M. Zamfirescu, F. Jipa, C. Luculescu, M. Dinescu, EC Buruiana, T. Buruiana, LE Sima, SM Petrescu. Abstract. In this work, 3D ...
The hydroxyapatite, obtained by chemical synthesis, is the main inorganic compound of bones and i... more The hydroxyapatite, obtained by chemical synthesis, is the main inorganic compound of bones and is very important due to its biocompatibility with the human organism to which it can directly adhere. There are numerous synthesis methods used at present because one has the purpose of obtaining a compound with the Ca/P atomic ratio as close to the theoretical one as posible, that is of 1.67. Two processes for obtaining hydroxyapatite of stoichiometric composition, the hydrothermal process and respectively microwave heating, were studied. Hydroxyapatite ceramic biocompatibility was demonstrated by cell viability tests as well as by scanning and fluorescence microscopy.
Tissue transglutaminase (TG2) is a member of the transglutaminase family that catalyzes Ca2+-depe... more Tissue transglutaminase (TG2) is a member of the transglutaminase family that catalyzes Ca2+-dependent protein crosslinks and hydrolyzes guanosine 5′-triphosphate (GTP). The conformation and functions of TG2 are regulated by Ca2+ and GTP levels; the TG2 enzymatically active open conformation is modulated by high Ca2+ concentrations, while high intracellular GTP promotes the closed conformation, with inhibition of the TG-ase activity. TG2’s unique characteristics and its ubiquitous distribution in the intracellular compartment, coupled with its secretion in the extracellular matrix, contribute to modulate the functions of the protein. Its aberrant expression has been observed in several cancer types where it was linked to metastatic progression, resistance to chemotherapy, stemness, and worse clinical outcomes. The N-terminal domain of TG2 binds to the 42 kDa gelatin-binding domain of fibronectin with high affinity, facilitating the formation of a complex with β-integrins, essential ...
Abstract During the last decade, graphene family nanomaterials (GFNs) have proven unique physicoc... more Abstract During the last decade, graphene family nanomaterials (GFNs) have proven unique physicochemical properties, with several applications being continuously explored. Among them, recent advances in nanomedicine revealed extensive interest for fabricating graphene-based cell-instructive environments for drug/gene delivery and cancer therapy, engineering stem cell responses, bacteria-killing and tissue engineering platforms, biosensing and cellular imaging. However, the full merging of GFN with bio-nanotechnology is still in its infancy, with many challenges remaining unexplored. The purpose of this chapter is to introduce a critical overview of the latest advances achieved in the synthesis and functionalization of graphene and its derivates for nanomedicine, as well as prospective expansion of this fascinating research field.
Due to their excellent mechanical and biocompatibility properties, titanium-based implants are su... more Due to their excellent mechanical and biocompatibility properties, titanium-based implants are successfully used as biomedical devices. However, when new bone formation fails for different reasons, impaired fracture healing becomes a clinical problem and affects the patient's quality of life. We aimed to design a new bioactive surface of titanium implants with a synergetic PEG biopolymer-based composition for gradual delivery of growth factors (FGF2, VEGF, and BMP4) during bone healing. The optimal architecture of non-cytotoxic polymeric coatings deposited by dip coating under controlled parameters was assessed both in cultured cells and in a rat tibial defect model (100% viability). Notably, the titanium adsorbed polymer matrix induced an improved healing process when compared with the individual action of each biomolecules. High-performance mass spectrometry analysis demonstrated that recovery after a traumatic event is governed by specific differentially regulated proteins, a...
Osseous implantology’s material requirements include a lack of potential for inducing allergic di... more Osseous implantology’s material requirements include a lack of potential for inducing allergic disorders and providing both functional and esthetic features for the patient’s benefit. Despite being bioinert, Zirconia ceramics have become a candidate of interest to be used as an alternative to titanium dental and cochlear bone-anchored hearing aid (BAHA) implants, implying the need for endowing the surface with biologically instructive properties by changing basic parameters such as surface texture. Within this context, we propose anisotropic and isotropic patterns (linear microgroove arrays, and superimposed crossline microgroove arrays, respectively) textured in zirconia substrates, as bioinstructive interfaces to guide the cytoskeletal organization of human mesenchymal stem cells (hMSCs). The designed textured micro-nano interfaces with either steep ridges and microgratings or curved edges, and nanoroughened walls obtained by direct femtosecond laser texturing are used to evaluate...
The modification of implant devices with biocompatible coatings has become necessary as a consequ... more The modification of implant devices with biocompatible coatings has become necessary as a consequence of premature loosening of prosthesis. This is caused mainly by chronic inflammation or allergies that are triggered by implant wear, production of abrasion particles, and/or release of metallic ions from the implantable device surface. Specific to the implant tissue destination, it could require coatings with specific features in order to provide optimal osseointegration. Pulsed laser deposition (PLD) became a well-known physical vapor deposition technology that has been successfully applied to a large variety of biocompatible inorganic coatings for biomedical prosthetic applications. Matrix assisted pulsed laser evaporation (MAPLE) is a PLD-derived technology used for depositions of thin organic material coatings. In an attempt to surpass solvent related difficulties, when different solvents are used for blending various organic materials, combinatorial MAPLE was proposed to grow t...
Here we describe a small-molecule inhibitor (SMI) that disrupts the tissue transglutaminase 2 (TG... more Here we describe a small-molecule inhibitor (SMI) that disrupts the tissue transglutaminase 2 (TG2)-fibronectin (FN) interaction. TG2 is a multifunctional protein, with enzymatic (transglutaminase, isopeptidase, protein disulfide isomerase), GTPase, and extracellular matrix (ECM) scaffold activities. TG2 directly interacts with FN through its N-terminus domain, playing an important role in stabilizing ternary TG2/FN/integrin complexes, which regulate cell adhesion to the matrix. Our group has previously shown that TG2 overexpressed in ovarian cancer (OC) promotes epithelial-to-mesenchymal transition (EMT) contributing to OC cell invasiveness and metastatic behavior. We showed that the interaction with FN is critical to these functions. Proximity ligation assay was used to measure TG2/integrin beta 1 interaction in OC tumors and identified TG2/integrin beta 1 complex in >50% of ovarian tumors, irrespective of histologic type. Based on those findings, we conducted the high-throughp...
Increasing evidence correlates the metastatic progression and post-chemotherapy recurrence of ova... more Increasing evidence correlates the metastatic progression and post-chemotherapy recurrence of ovarian cancer (OC) to a small population of cancer stem cells (CSCs), resistant to traditional chemotherapy and responsible for tumor relapse. Tissue transglutaminase (TG2) is a multifunctional protein, with enzymatic and scaffold functions, overexpressed in ovarian carcinomas, where it promotes metastasis. Independently of its enzymatic function, TG2 can be secreted in the extracellular compartment where it increases cell adhesion to the fibronectin (FN) matrix by regulating integrins clustering and matrix reorganization. We hypothesized that by binding to the integrins and FN, TG2 promotes survival of CSCs and supports OC spheroid formation. Our data demonstrate that TG2, β1 integrin, and FN1 expression are markedly increased in OC spheroids compared with monolayers and are enriched in successive sphere generations. Immunofluorescence (IF) staining supports that TG2 forms abundant comple...
Our study focused on the long-term degradation under simulated conditions of coatings based on di... more Our study focused on the long-term degradation under simulated conditions of coatings based on different compositions of polycaprolactone-polyethylene glycol blends (PCL-blend-PEG), fabricated for titanium implants by a dip-coating technique. The degradation behavior of polymeric coatings was evaluated by polymer mass loss measurements of the PCL-blend-PEG during immersion in SBF up to 16 weeks and correlated with those yielded from electrochemical experiments. The results are thoroughly supported by extensive compositional and surface analyses (FTIR, GIXRD, SEM, and wettability investigations). We found that the degradation behavior of PCL-blend-PEG coatings is governed by the properties of the main polymer constituents: the PEG solubilizes fast, immediately after the immersion, while the PCL degrades slowly over the whole period of time. Furthermore, the results evidence that the alteration of blend coatings is strongly enhanced by the increase in PEG content. The biological asses...
The ability of commercial monolayer graphene oxide (GO) and graphene oxide nanocolloids (GOC) to ... more The ability of commercial monolayer graphene oxide (GO) and graphene oxide nanocolloids (GOC) to interact with different unicellular systems and biomolecules was studied by analyzing the response of human alveolar carcinoma epithelial cells, the yeast Saccharomyces cerevisiae and the bacteria Vibrio fischeri to the presence of different nanoparticle concentrations, and by studying the binding affinity of different microbial enzymes, like the α-l-rhamnosidase enzyme RhaB1 from the bacteria Lactobacillus plantarum and the AbG β-d-glucosidase from Agrobacterium sp. (strain ATCC 21400). An analysis of cytotoxicity on human epithelial cell line A549, S. cerevisiae (colony forming units, ROS induction, genotoxicity) and V. fischeri (luminescence inhibition) cells determined the potential of both nanoparticle types to damage the selected unicellular systems. Also, the protein binding affinity of the graphene derivatives at different oxidation levels was analyzed. The reported results highl...
Eyes absent (EYA) are non-thiol-based protein tyrosine phosphatases (PTPs) that also have transcr... more Eyes absent (EYA) are non-thiol-based protein tyrosine phosphatases (PTPs) that also have transcriptional co-activator functions. Their PTP activity is involved in various pathologies. Recently, we demonstrated that Src tyrosine kinase phosphorylates human EYA3 by controlling its subcellular localization. We also found EYA3′s ability to autodephosphorylate, while raising the question if the two opposing processes could be involved in maintaining a physiologically adequate level of phosphorylation. Using native and bottom-up mass spectrometry, we performed detailed mapping and characterization of human EYA3 Src-phosphorylation sites. Thirteen tyrosine residues with different phosphorylation and autodephosphorylation kinetics were detected. Among these, Y77, 96, 237, and 508 displayed an increased resistance to autodephosphorylation. Y77 and Y96 were found to have the highest impact on the overall EYA3 phosphorylation. Using cell cycle analysis, we showed that Y77, Y96, and Y237 are i...
The potential of mesenchymal stem cells (MSCs) for implantology and cell-based therapy represents... more The potential of mesenchymal stem cells (MSCs) for implantology and cell-based therapy represents one of the major ongoing research subjects within the last decades. In bone regeneration applications, the various environmental factors including bioactive compounds such as growth factors, chemicals and physical characteristics of biointerfaces are the key factors in controlling and regulating osteogenic differentiation from MSCs. In our study, we have investigated the influence of Lactoferrin (Lf) and Hydroxyapatite (HA) embedded within a biodegradable PEG-PCL copolymer on the osteogenic fate of MSCs, previous studies revealing an anti-inflammatory potential of the coating and osteogenic differentiation of murine pre-osteoblast cells. The copolymer matrix was obtained by the Matrix Assisted Pulsed Laser Evaporation technique (MAPLE) and the composite layers containing the bioactive compounds (Lf, HA, and Lf-HA) were characterised by Scanning Electron Microscopy and Atomic Force Micro...
Cancer⁻stroma interactions play a key role in cancer progression and response to standard chemoth... more Cancer⁻stroma interactions play a key role in cancer progression and response to standard chemotherapy. Here, we provide a summary of the mechanisms by which the major cellular components of the ovarian cancer (OC) tumor microenvironment (TME) including cancer-associated fibroblasts (CAFs), myeloid, immune, endothelial, and mesothelial cells potentiate cancer progression. High-grade serous ovarian cancer (HGSOC) is characterized by a pro-inflammatory and angiogenic signature. This profile is correlated with clinical outcomes and can be a target for therapy. Accumulation of malignant ascites in the peritoneal cavity allows for secreted factors to fuel paracrine and autocrine circuits that augment cancer cell proliferation and invasiveness. Adhesion of cancer cells to the mesothelial matrix promotes peritoneal tumor dissemination and represents another attractive target to prevent metastasis. The immunosuppressed tumor milieu of HGSOC is permissive for tumor growth and can be modulate...
Abstract In this study, coatings based on lysozyme embedded into a matrix of polyethylene glycol ... more Abstract In this study, coatings based on lysozyme embedded into a matrix of polyethylene glycol (PEG) and polycaprolactone (PCL) were fabricated by two different methods (Matrix Assisted Pulsed Laser Evaporation – MAPLE and Dip Coating) for obtaining antimicrobial coatings envisaged for long term medical applications. Coatings with different PEG:PCL compositions (3:1; 1:1; 1:3) were synthesized in order to evaluate the antimicrobial activity of lysozyme embedded into the polymeric matrix. The main surface features, such as roughness and wettability, with impact on the microbial adhesion as well as on the eukaryote cell function were measured. The obtained composite coatings exhibited a significant antibacterial activity against Escherichia coli, Bacillus subtilis, Enterococcus faecalis and Staphylococcus aureus strains. As well, specific blended coatings showed appropriate viability, good spreading and normal cell morphology of SaOs2 human osteoblasts and mesenchymal stem cells (MSCs). These investigations highlight the suitability of biodegradable composites as implant coatings for decreasing the risk of bacterial contamination associated with prosthetic procedures.
The bipotent nature of the HepaRG cell line is a unique property among human hepatoma-derived cel... more The bipotent nature of the HepaRG cell line is a unique property among human hepatoma-derived cells. Cell treatment with specific differentiation inducers results in a mixture of hepatocyte- and biliary-like cells, accompanied by upregulation of liver-specific proteins, drug metabolizing enzymes, transcription regulators, membrane receptors or innate immune response effectors. These features make the HepaRG cells a suitable and handy replacement for primary hepatocytes, to study hepatic functions in vitro. However, cell differentiation is a long, variable process, requiring special culture conditions, while the resulting mixed cell populations is usually a major drawback. This process can potentially be controlled by interface characteristics, such as substrate topography. To screen for such novel substrates, we have first developed a new HepaRG cell line, designated as HepaRGDsRed, expressing the reporter gene DsRed. The fluorescent protein was expressed in hepatocyte- and not biliary-like cells, in a differentiation dependent-manner. We have further used replicated microstructured gradients of polydimethylsiloxane (PDMS) that allow three-dimensional manipulation in vitro, to monitor HepaRGDsRed differentiation in real time. We demonstrate that this approach enables the controlled assembly of viable hepatocyte-like cells for functional studies, which can be maintained in culture without loss of differentiation. The regulated expression of the DsRed reporter proved a valuable tool not only for rapid screening of novel cell growth substrates favoring cell differentiation, but also, to enrich the hepatocyte-like cell population by fluorescence-activated cell sorting to investigate liver-specific processes in vitro.
Two Photon Polymerization of Ormosils. [AIP Conference Proceedings 1278, 843 (2010)]. A. Matei, M... more Two Photon Polymerization of Ormosils. [AIP Conference Proceedings 1278, 843 (2010)]. A. Matei, M. Zamfirescu, F. Jipa, C. Luculescu, M. Dinescu, EC Buruiana, T. Buruiana, LE Sima, SM Petrescu. Abstract. In this work, 3D ...
The hydroxyapatite, obtained by chemical synthesis, is the main inorganic compound of bones and i... more The hydroxyapatite, obtained by chemical synthesis, is the main inorganic compound of bones and is very important due to its biocompatibility with the human organism to which it can directly adhere. There are numerous synthesis methods used at present because one has the purpose of obtaining a compound with the Ca/P atomic ratio as close to the theoretical one as posible, that is of 1.67. Two processes for obtaining hydroxyapatite of stoichiometric composition, the hydrothermal process and respectively microwave heating, were studied. Hydroxyapatite ceramic biocompatibility was demonstrated by cell viability tests as well as by scanning and fluorescence microscopy.
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