- Biomaterials and Tissue Engineering, Stem cell and Regenerative medicine, Cell Biology, Biochemistry, Clinical Biochemistry, Cell Culture, and 23 moreCancer, Stem Cell Biology, Stem Cell Research, Tissue Engineering: Hard Tissue Engineering (Bone Substitutes and Implants),Bioceramics such as Calcium Phosphate Especially Hydroxyapatite and Beta Tricalcium Phosphate, Porous Bioceramics for Bone Implants, Tissue Regeneration, Animal Tissue Culture, Tissue engineering and regenerative medicine, Cancer Research, Inflammatory Immune Response, Molecular Biology, Aging, Apoptosis, Oncology, Molecular and cellular biology, Genetics, Biotechnology, Neuroscience, Cognitive Sciences, Nanomaterials, Biomaterials, Nanobiotechnology, Nano Fabrication, Nanoscience, and Nanotechnologyedit
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Abstract Understanding and controlling natural and synthetic biointerfaces is known to be the key to a wide variety of application within cell culture and tissue engineering field. As both material characteristics and methods are... more
Abstract Understanding and controlling natural and synthetic biointerfaces is known to be the key to a wide variety of application within cell culture and tissue engineering field. As both material characteristics and methods are important in tailoring biointerfaces characteristics, in this work we explore the feasibility of using Matrix Assisted Pulsed Laser Evaporation technique for obtaining synthetic copolymeric biocoatings ( i.e. poly(ethylene glycol)-block-poly(ɛ-caprolactone) methyl ether) for evaluating in vitro Vero and MC3T3-E1 pre-osteoblasts cell response. Characterization and evaluation of the coated substrates were carried out using different techniques. The Fourier transform infrared spectroscopy data demonstrated that the main functional groups in the MAPLE-deposited films remained intact. Atomic Force Microscopy images showed the coatings to be continuous, with the surface roughness depending on the deposition parameters. Moreover, the behaviour of the coatings in medium mimicking the pH and temperature of the human body was studied and corelated to degradation. Spectro-ellipsometry (SE) and AFM measurements revealed the degradation trend during immersion time by the changes in coating thickness and roughness. In vitro biocompatibility was studied by indirect contact tests on Vero cells in accordance with ISO 10993-5/2009. The results obtained in terms of cell morphology (phase contrast microscopy) and cytotoxicity (LDH and MTT assays) proved biocompatibility. Furthermore, direct contact assays on MC3T3-E1 pre-osteoblasts demonstrated the capacity of all analyzed specimens to support cell adhesion, normal cellular morphology and growth.
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Abstract In this work, we propose a new design for biodegradable composite coatings obtained by laser methods, which are aimed at evaluating the effects of active antitumoral elements on osteosarcoma cells. Our approach relies on... more
Abstract In this work, we propose a new design for biodegradable composite coatings obtained by laser methods, which are aimed at evaluating the effects of active antitumoral elements on osteosarcoma cells. Our approach relies on embedding curcumin, which is a natural polyphenol having antitumoral properties, within biodegradable copolymer coatings (i.e. polyvinyl alcohol-polyethylene glycol − PVA-PEG) by using matrix assisted pulsed laser evaporation (MAPLE). The structural and morphological characteristics of the coatings were tailored by using different solvents (water, ethanol, benzene, dimethylsufoxide) as deposition matrix. The morphological characteristics of the resulting films were investigated by atomic force microscopy (AFM), whereas their chemical composition was characterized by Fourier transform infrared spectroscopy (FTIR). These characteristics were correlated with the degradation behavior by using ellipsometry (SE) and AFM measurements data. The in vitro study of the MG-63 osteosarcoma cell behavior indicates that the developed hybrid coatings significantly decreased osteosarcoma cell viability and proliferation potential. The physico-chemical characteristics of the thin films, along with the preliminary in vitro analyses, suggest that our developed polymeric hybrid coatings represent an efficient way to tackle the design of antitumoral surfaces, with applications in biomedicine.
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Herein, three different recipes of multi-component hydrogels were synthesized by e-beam irradiation. These hydrogels were obtained from aqueous polymer mixtures in which different proportions of bovine collagen gel, sodium... more
Herein, three different recipes of multi-component hydrogels were synthesized by e-beam irradiation. These hydrogels were obtained from aqueous polymer mixtures in which different proportions of bovine collagen gel, sodium carboxymethylcellulose (CMC), poly(vinylpyrrolidone), chitosan, and poly(ethylene oxide) were used. The cross-linking reaction was carried out exclusively by e-beam cross-linking at 25 kGy, a dose of irradiation sufficient both to complete the cross-linking reaction and effective for hydrogel sterilization. The hydrogels developed in this study were tested in terms of physical and chemical stability, mechanical, structural, morphological, and biological properties. They are transparent, maintain their structure, are non-adhesive when handling, and most importantly, especially from the application point of view, have an elastic structure. Likewise, these hydrogels possessed different swelling degrees and expressed rheological behavior characteristic of soft solids ...
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In recent years, the role of zinc in biological systems has been a subject of intense research. Zinc is required for multiple metabolic processes as a structural, regulatory, or catalytic ion. The objective of this study, was to assess... more
In recent years, the role of zinc in biological systems has been a subject of intense research. Zinc is required for multiple metabolic processes as a structural, regulatory, or catalytic ion. The objective of this study, was to assess the toxicity profile of a newly synthesized zinc-boron molecule on cultured cells. Zinc fructoborate, at different levels of concentration, was tested for its impact on the Vero kidney cell line (ATCC® CCL-81™) using the MTT assay. The compound exhibited a low cytotoxic effect on the cell line. Thus, our study demonstrates that the zinc fructoborate could become a promising dietary supplement molecule.
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Osseointegration plays the most important role in the success of an implant. One of the applications of hydroxyapatite (HAp) is as a coating for metallic implants due to its bioactive nature, which improves osteoconduction. The purpose of... more
Osseointegration plays the most important role in the success of an implant. One of the applications of hydroxyapatite (HAp) is as a coating for metallic implants due to its bioactive nature, which improves osteoconduction. The purpose of this research was to assess the in vitro behavior of HAp undoped and doped with Ag and/or Sr obtained by galvanostatic pulsed electrochemical deposition. The coatings were investigated in terms of chemical bonds, contact angle and surface free energy, electrochemical behavior, in vitro biomineralization in acellular media (SBF and PBS), and biocompatibility with preosteoblasts cells (MC3T3-E1 cell line). The obtained results highlighted the beneficial impact of Ag and/or Sr on the HAp. The FTIR spectra confirmed the presence of hydroxyapatite within all coatings, while in terms of wettability, the contact angle and surface free energy investigations showed that all surfaces were hydrophilic. The in vitro behavior of MC3T3-E1 indicated that the pres...
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Nowadays, using polymers with specific characteristics to coat the surface of a device to prevent undesired biological responses can represent an optimal strategy for developing new and more efficient implants for biomedical applications.... more
Nowadays, using polymers with specific characteristics to coat the surface of a device to prevent undesired biological responses can represent an optimal strategy for developing new and more efficient implants for biomedical applications. Among them, zwitterionic phosphorylcholine-based polymers are of interest due to their properties to resist cell and bacterial adhesion. In this work, the Matrix-Assisted Laser Evaporation (MAPLE) technique was investigated as a new approach for functionalising Polydimethylsiloxane (PDMS) surfaces with zwitterionic poly(2-Methacryloyloxyethyl-Phosphorylcholine) (pMPC) polymer. Evaluation of the physical–chemical properties of the new coatings revealed that the technique proposed has the advantage of achieving uniform and homogeneous stable moderate hydrophilic pMPC thin layers onto hydrophobic PDMS without any pre-treatment, therefore avoiding the major disadvantage of hydrophobicity recovery. The capacity of modified PDMS surfaces to reduce bacter...
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A 3D biodegradable protein based matrix for cartilage tissue engineering and stem cell differentiation to cartilage
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Due to their superior mechanical and chemical properties, titanium (Ti) and its alloys have been widely used as orthopedic implantable devices. However, their bioinertness represents a limitation, which can be overcome by employing... more
Due to their superior mechanical and chemical properties, titanium (Ti) and its alloys have been widely used as orthopedic implantable devices. However, their bioinertness represents a limitation, which can be overcome by employing various surface modifications, such as TiO2 nanotube (TNT) fabrication via electrochemical anodization. Anodic TNTs present tunable dimensions and unique structures, turning them into feasible drug delivery platforms. In the present work, TNTs were loaded with icariin (Ica) through an adhesive intermediate layer of polydopamine (DP), and their in vitro and in vivo biological performance was evaluated. The successful fabrication of the modified surfaces was verified by scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), and contact angle measurements (CA), while the in vitro release of Ica was evaluated via UV-VIS spectrophotometry. In terms of in vitro behaviour, comparative studies on RAW 264...
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SiC- and Ag-SiC-doped hydroxyapatite (HA) coatings were deposited via magnetron sputtering aiming at increased corrosion protection of Ti-10Nb-10Zr-5Ta alloy in simulated body fluid environment and superior mechanical properties compared... more
SiC- and Ag-SiC-doped hydroxyapatite (HA) coatings were deposited via magnetron sputtering aiming at increased corrosion protection of Ti-10Nb-10Zr-5Ta alloy in simulated body fluid environment and superior mechanical properties compared to plain hydroxyapatite. The coatings had a total thickness of about 350 nm. The X ray diffraction patterns indicate that HA coatings are polycrystalline with a hexagonal structure and the addition of SiC determined the coating amorphization. All coatings presented a lower roughness compared to the Ti alloy and were hydrophilic. Ag-SiC-HA coating presented the best corrosion resistance and tribological parameters. All coatings were biocompatible, as ascertained via indirect cytocompatibility studies conducted on Vero cells.
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Titanium alloys are widely used for biomedical applications due to their good biocompatibility. Nevertheless, they cannot be used for balloon expandable stents due to a lack of ductility compared to cobalt-chromium (Co-Cr) alloys and... more
Titanium alloys are widely used for biomedical applications due to their good biocompatibility. Nevertheless, they cannot be used for balloon expandable stents due to a lack of ductility compared to cobalt-chromium (Co-Cr) alloys and stainless steels. In this study, a new highly deformable Ti-16Nb-8Mo alloy was designed for such an application. However, the biological performance of a stent material is strongly influenced by the effect exerted on the behavior of endothelial cells. Therefore, the cellular responses of human umbilical vein endothelial cells (HUVECs), including morphological characteristics, cell viability and proliferation, and functional markers expression, were investigated to evaluate the biocompatibility of the alloy in the present study. The in vitro results demonstrated the suitability of this alloy for use as endovascular stents.
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GNP–SS functionalized Gum alloy exhibits superior bioactivity in inducing in vitro osteogenesis.
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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... more
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 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 r...
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The improvement in the research area of the implant by surface functionalization when correlated with the biological response is of major interest in the biomedical field. Based on the fact that the inflammatory response is directly... more
The improvement in the research area of the implant by surface functionalization when correlated with the biological response is of major interest in the biomedical field. Based on the fact that the inflammatory response is directly involved in the ultimate response of the implant within the body, it is essential to study the macrophage-material interactions. Within this context, we have investigated the composite material-macrophage cell interactions and the inflammatory response to these composites with amorphous hydroxyapatite (HA), Lactoferrin (Lf), and polyethylene glycol-polycaprolactone (PEG-PCL) copolymer. All materials are obtained by Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique and characterized by Atomic Force Microscopy and Scanning Electron Microscopy. Macrophage-differentiated THP-1 cells proliferation and metabolic activity were assessed by qualitative and quantitative methods. The secretion of tumor necrosis factor alpha (TNF-α) and interleukin 10 (IL-1...
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In vitro biocompatibility of zirconium oxide was investigated in comparison with titanium, which is considered the gold standard for medical implants, by using hFOB 1.19 osteoblastic cell line. The viability of osteoblasts was evaluated... more
In vitro biocompatibility of zirconium oxide was investigated in comparison with titanium, which is considered the gold standard for medical implants, by using hFOB 1.19 osteoblastic cell line. The viability of osteoblasts was evaluated by MTT and LDH tests that demonstrated the absence of any cytostatic or cytotoxic effect. Immunocytochemical staining of fibronectin, showed the capacity of these cells to elaborate extracellularly large amounts of this important adhesive protein, suggesting a good cell adhesion to both materials. Despite the differences in cell morphology and orientation, fluorescence microscopy studies of β-integrins and some cytoskeletal proteins revealed almost identical immunolabeling patterns in the cells grown on titanium and zirconia substrates. Cell proliferation, evaluated by bromodeoxyuridine (BrdU) incorporation assay and Proliferating Cell Nuclear Antigen (PCNA) analysis, was similar in both situations. Zymographic analysis of gelatinolytic activities sp...
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The aim of this study was to evaluate the capacity of human osteoarthritic chondrocytes to synthesize the cartilage matrix components: chondroitin sulfate (CS), keratan sulfate (KS) and colagens (COL). The study was performed on cells... more
The aim of this study was to evaluate the capacity of human osteoarthritic chondrocytes to synthesize the cartilage matrix components: chondroitin sulfate (CS), keratan sulfate (KS) and colagens (COL). The study was performed on cells embedded in type II collagen gel. Specific COL staining and glycosaminoglycan (CS, KS) immunohistochemical examinations demonstrated that the osteoarthritic cartilage cells maintain their anabolic ability. Despite the biosynthetic activity displayed by chondrocytes, a net loss of the extracellular matrix represents the hallmark of all stages of osteoarthritic cartilage degeneration. This leads to the assumption that overall enzymatic degradation of the extracellular matrix components might be the reason for the metabolic imbalance in osteoarthritic cartilage. Type II collagen gel obtained from bovine tracheal cartilage proved to be a good chondrocyte support for studying cartilage extracellular matrix turnover.
To modulate the biofunctionality of implantable medical devices commonly used in clinical practice, their surface modification with bioactive polymeric coatings is an attractive and successful emerging strategy. Biodegradable coatings... more
To modulate the biofunctionality of implantable medical devices commonly used in clinical practice, their surface modification with bioactive polymeric coatings is an attractive and successful emerging strategy. Biodegradable coatings based on poly(lactic acid-co-glycolic acid), PLGA, represent versatile and safe candidates for surface modification of implantable biomaterials and devices, providing additional tunable ability for topical delivery of desired therapeutic agents. In the present study, Ibuprofen-loaded PLGA coatings (PLGA/IBUP) were obtained by using the dip-coating and drop-casting combined protocol. The composite materials demonstrated long-term drug release under biologically simulated dynamic conditions. Reversible swelling phenomena of polymeric coatings occurred in the first two weeks of testing, accompanied by the gradual matrix degradation and slow release of the therapeutic agent. Irreversible degradation of PLGA coatings occurred after one month, due to copolym...
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Calcium carbonate from marble and seashells is an eco-friendly, sustainable, and largely available bioresource for producing natural bone-like calcium phosphates (CaPs). Based on three main objectives, this research targeted the: (i)... more
Calcium carbonate from marble and seashells is an eco-friendly, sustainable, and largely available bioresource for producing natural bone-like calcium phosphates (CaPs). Based on three main objectives, this research targeted the: (i) adaptation of an indirect synthesis route by modulating the amount of phosphorus used in the chemical reaction, (ii) comprehensive structural, morphological, and surface characterization, and (iii) biocompatibility assessment of the synthesized powdered samples. The morphological characterization was performed on digitally processed scanning electron microscopy (SEM) images. The complementary 3D image augmentation of SEM results also allowed the quantification of roughness parameters. The results revealed that both morphology and roughness were modulated through the induced variation of the synthesis parameters. Structural investigation of the samples was performed by Fourier transform infrared spectroscopy and X-ray diffraction. Depending on the phosph...
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ZnO materials with spherical morphology, core-shell and solid, disperse or interconnected, were obtained by a completely green synthesis via a carbohydrate-template route. Morphology, structure and optical properties, as well as... more
ZnO materials with spherical morphology, core-shell and solid, disperse or interconnected, were obtained by a completely green synthesis via a carbohydrate-template route. Morphology, structure and optical properties, as well as antimicrobial potential and cytocompatibility were investigated. The antimicrobial efficiency of the obtained materials was screened against a large spectrum of reference and clinical microbial strains, both susceptible and exhibiting resistance phenotypes of clinical and epidemiological interest, in planktonic and biofilm state. Their biocidal activity is strongly dependent of material's characteristics and target microorganism. One of the most valuable findings of our study is the good antibiofilm activity of the obtained nanostructures, which in some cases was superior to that noted against planktonic cells, despite the well-known high tolerance of biofilm-embedded cells to different stressor agents. Another important finding is the excellent efficiency against three Gram-negative, respectively Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae and two Gram-positive species, i.e. Staphylococcus aureus and Enteroccus faecium included in the ESKAPE list of the most dangerous resistant pathogens, requiring global surveillance and urgent need for the development of novel antimicrobial agents. Our study offers the first insight regarding the high therapeutic potential of ZnO nanoparticles against the fearful nosocomial pathogen A. baumannii. The cytocompatibility of the developed materials in terms of cell morphology, viability and proliferation, revealed a comparable dose-dependent cellular response, at the active antimicrobial concentrations, only a low effect on cell viability is evidenced. Overall, our data demonstrated the potential of the materials for antimicrobial applications and also that their biotoxicity can be modulated directly through their morpho-structural characteristics.
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The critical role of the immune system in host defense against foreign bodies and pathogens has been long recognized. With the introduction of a new field of research called osteoimmunology, the crosstalk between the immune and... more
The critical role of the immune system in host defense against foreign bodies and pathogens has been long recognized. With the introduction of a new field of research called osteoimmunology, the crosstalk between the immune and bone-forming cells has been studied more thoroughly, leading to the conclusion that the two systems are intimately connected through various cytokines, signaling molecules, transcription factors and receptors. The host immune reaction triggered by biomaterial implantation determines the in vivo fate of the implant, either in new bone formation or in fibrous tissue encapsulation. The traditional biomaterial design consisted in fabricating inert biomaterials capable of stimulating osteogenesis; however, inconsistencies between the in vitro and in vivo results were reported. This led to a shift in the development of biomaterials towards implants with osteoimmunomodulatory properties. By endowing the orthopedic biomaterials with favorable osteoimmunomodulatory pr...
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ABSTRACT A 3D biodegradable protein based matrix for cartilage tissue engineering and stem cell differentiation to cartilage
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TiO2 nanostructures and more specifically nanotubes have gained significant attention in biomedical applications, due to their controlled nanoscale topography in the sub-100 nm range, high surface area, chemical resistance, and... more
TiO2 nanostructures and more specifically nanotubes have gained significant attention in biomedical applications, due to their controlled nanoscale topography in the sub-100 nm range, high surface area, chemical resistance, and biocompatibility. Here we review the crucial aspects related to morphology and properties of TiO2 nanotubes obtained by electrochemical anodization of titanium for the biomedical field. Following the discussion of TiO2 nanotopographical characterization, the advantages of anodic TiO2 nanotubes will be introduced, such as their high surface area controlled by the morphological parameters (diameter and length), which provides better adsorption/linkage of bioactive molecules. We further discuss the key interactions with bone-related cells including osteoblast and stem cells in in vitro cell culture conditions, thus evaluating the cell response on various nanotubular structures. In addition, the synergistic effects of electrical stimulation on cells for enhancing...
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Due to its excellent bone-like mechanical properties and non-toxicity, magnesium (Mg) and its alloys have attracted great interest as biomaterials for orthopaedic applications. However, their fast degradation rate in physiological... more
Due to its excellent bone-like mechanical properties and non-toxicity, magnesium (Mg) and its alloys have attracted great interest as biomaterials for orthopaedic applications. However, their fast degradation rate in physiological environments leads to an acute inflammatory response, restricting their use as biodegradable metallic implants. Endowing Mg-based biomaterials with immunomodulatory properties can help trigger a desired immune response capable of supporting a favorable healing process. In this study, electrospun poly(ε-caprolactone) (PCL) fibers loaded with coumarin (CM) and/or zinc oxide nanoparticles (ZnO) were used to coat the commercial AZ31 Mg alloy as single and combined formulas, and their effects on the macrophage inflammatory response and osteoclastogenic process were investigated by indirect contact studies. Likewise, the capacity of the analyzed samples to generate reactive oxygen species (ROS) has been investigated. The data obtained by attenuated total reflect...
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Mucoadhesive films can be used to extend the action of different bioactive compounds in the oral cavity. [...]
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Recent advancements in biomedicine have focused on designing novel and stable interfaces that can drive a specific cellular response toward the requirements of medical devices or implants. Among these, in recent years, electroactive... more
Recent advancements in biomedicine have focused on designing novel and stable interfaces that can drive a specific cellular response toward the requirements of medical devices or implants. Among these, in recent years, electroactive polymers (i.e., polyvinylidene fluoride or PVDF) have caught the attention within the biomedical applications sector, due to their insolubility, stability in biological media, in vitro and in vivo non-toxicity, or even piezoelectric properties. However, the main disadvantage of PVDF-based bio-interfaces is related to the absence of the functional groups on the fluoropolymer and their hydrophobic character leading to a deficiency of cell adhesion and proliferation. This work was aimed at obtaining hydrophilic functional PVDF polymer coatings by using, for the first time, the one-step, matrix-assisted pulsed evaporation (MAPLE) method, testing the need of a post-deposition thermal treatment and analyzing their preliminary capacity to support MC3T3-E1 pre-o...
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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... 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...
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Titanium dioxide (TiO2) nanotube coated substrates have revolutionized the concept of implant in a number of ways, being endowed with superior osseointegration properties and local drug delivery capacity. While accumulating reports... more
Titanium dioxide (TiO2) nanotube coated substrates have revolutionized the concept of implant in a number of ways, being endowed with superior osseointegration properties and local drug delivery capacity. While accumulating reports describe the influence of nanotube diameter on cell behavior, little is known about the effects of nanotube lateral spacing on cells involved in bone regeneration. In this context, in the present study the MC3T3-E1 murine pre-osteoblast cells behavior has been investigated by using TiO2 nanotubes of ~78 nm diameter and lateral spacing of 18 nm and 80 nm, respectively. Both nanostructured surfaces supported cell viability and proliferation in approximately equal extent. However, obvious differences in the cell spreading areas, morphologies, the organization of the actin cytoskeleton and the pattern of the focal adhesions were noticed. Furthermore, investigation of the pre-osteoblast differentiation potential indicated a higher capacity of larger spacing na...
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: TiO2 nanotubes (TNTs) are attractive nanostructures for localized drug delivery. Owing to their excel¬lent biocompatibility and physicochemical properties, numerous functionalizations of TNTs have been attempted for their use as... more
: TiO2 nanotubes (TNTs) are attractive nanostructures for localized drug delivery. Owing to their excel¬lent biocompatibility and physicochemical properties, numerous functionalizations of TNTs have been attempted for their use as therapeutic agent delivery platforms. In this review, we discuss the current advances in the applications of TNT-based delivery systems with an emphasis on the various functionalizations of TNTs for enhancing osteogenesis at the bone–implant interface and for preventing implant-related infection. Innovation of therapies for enhancing osteogenesis still represents a critical challenge in regeneration of bone defects. The overall concept focuses on the use of osteoconductive materials in combination with the use of osteoinductive or osteopromotive factors. In this context, we highlight the strategies for improving the functionality of TNTs, using five classes of bioactive agents: growth factors (GFs), statins, plant derived molecules, inorganic therapeutic ions/nanoparticles (NPs) and antimicrobial compounds.