ABSTRACT
BACKGROUND: Bisphosphonates are widely employed drugs for the treatment of pathologies with high bone resorption, such as osteoporosis, and display a great affinity for calcium ions and apatitic substrates. Here, we aimed to investigate the potentiality of zoledronate functionalized hydroxyapatite nanocrystals (HAZOL) to promote bone regeneration by stimulating adhesion, viability, metabolic activity and osteogenic commitment of human bone marrow derived mesenchymal stromal cells (hMSCs). METHODS: we adopted an advanced three-dimensional (3D) in vitro fracture healing model to study porous scaffolds: hMSCs were seeded onto the scaffolds that, after three days, were cut in halves and unseeded scaffolds were placed between the two halves. Scaffold characterization by X-ray diffraction, transmission and scanning electron microscopy analyses and cell morphology, viability, osteogenic differentiation and extracellular matrix deposition were evaluated after 3, 7 and 10 days of culture. RESULTS: Electron microscopy showed a porous and interconnected structure and a uniform cell layer spread onto scaffolds. Scaffolds were able to support cell growth and cells progressively colonized the whole inserts in absence of cytotoxic effects. Osteogenic commitment and gene expression of hMSCs were enhanced with higher expressions of ALPL, COL1A1, BGLAP, RUNX2 and Osterix genes. CONCLUSION: Although some limitations affect the present study (e.g., the lack of longer experimental times, of mechanical stimulus or pathological microenvironment), the obtained results with the adopted experimental setup suggested that zoledronate functionalized scaffolds (GHAZOL) might sustain not only cell proliferation, but positively influence osteogenic differentiation and activity if employed in bone fracture healing.
Subject(s)
Mesenchymal Stem Cells , Osteogenesis , Bone Marrow , Bone Marrow Cells , Bone Regeneration , Cell Differentiation , Cell Proliferation , Cells, Cultured , Humans , Mesenchymal Stem Cells/metabolism , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Zoledronic Acid/pharmacologyABSTRACT
This paper investigates the electrochemical properties of a new Cu(II)-based metal-organic framework (MOF). Noted as Cu-YBDC, it is built upon a linker containing the propargyl carbamate functionality and immobilized on a glassy carbon electrode by drop-casting (GC/Cu-YBDC). Afterward, GC/Cu-YBDC was treated with HAuCl4 and the direct electro-deposition of Au nanoparticles was carried at 0.05 V for 600 s (GC/Au/Cu-YBDC). The performance of both electrodes towards nitrite oxidation was tested and it was found that GC/Au/Cu-YBDC exhibited a better electrocatalytic behavior toward the oxidation of nitrite than GC/Cu-YBDC with enhanced catalytic currents and a reduced nitrite overpotential from 1.20 to 0.90 V. Additionally GC/Au/Cu-YBDC showed a low limit of detection (5.0 µM), an ultrafast response time (<2 s), and a wide linear range of up to 8 mM in neutral pH.
Subject(s)
Metal Nanoparticles , Metal-Organic Frameworks , Carbamates , Copper , Electrochemical Techniques , Electrodes , Gold , Ligands , Limit of Detection , Nitrites , Phthalic AcidsABSTRACT
Despite alternatives to autogenous bone graft for spinal fusion have been investigated, it has been shown that osteoconductive materials alone do not give a rate of fusion comparable with autogenous bone. This study analyzed a strontium substituted ß-tricalcium phosphate (Sr-ßTCP) associated with syngeneic, unexpanded, and undifferentiated mesenchymal stem cells from bone marrow (BMSC) or adipose tissue (ADSC) as a new tissue engineering approach for spinal fusion procedures. A posterolateral fusion was performed in 15 ovariectomized (OVX) and 15 sham-operated (SHAM) Inbred rats. Both SHAM and OVX animals were divided into three groups: Sr-ßTCP, Sr-ßTCP + BMCSs, and Sr-ßTCP + ADSCs. Animals were euthanized 8 weeks after surgery and the spines evaluated by manual palpation, micro-CT, and histology. For both SHAM and OVX animals, the fusion tissue in the Sr-ßTCP + BMSCs group was more solid. This effect was significantly higher in OVX animals by comparing the Sr-ßTCP + BMCSs group with Sr-ßTCP + ADSCs. Radiographical score, based on micro-CT 2D image, highlighted that the Sr-ßTCP + BMCSs group presented a similar fusion to Sr-ßTCP and higher than Sr-ßTCP + ADSCs in both SHAM and OVX animals. Micro-CT 3D parameters did not show significant differences among groups. Histological score showed significantly higher fusion in Sr-ßTCP + BMSCs group than Sr-ßTCP and Sr-ßTCP + ADSCs, for both SHAM and OVX animals. In conclusion, our results suggest that addition of BMSCs to a Sr-ßTCP improve bone formation and fusion, both in osteoporotic and nonosteoporotic animal, whereas spinal fusion is not enhanced in rats treated with Sr-ßTCP + ADSCs. Thus, for conducting cells therapy in spinal surgery BMSCs still seems to be a better choice compared with ADSCs.
Subject(s)
Adipose Tissue/drug effects , Bone Marrow/drug effects , Calcium Phosphates/pharmacology , Mesenchymal Stem Cells/drug effects , Osteogenesis/drug effects , Strontium/pharmacology , Animals , Bone Regeneration/drug effects , Female , Lumbar Vertebrae/drug effects , Mesenchymal Stem Cell Transplantation/methods , Osteoporosis/drug therapy , Ovariectomy/methods , Rats , Spinal Fusion/methods , Tissue Engineering/methodsABSTRACT
The possibility to functionalize calcium phosphates with bioactive agents is a promising strategy to design innovative biomaterials for bone repair able to couple the bioactive properties of the inorganic compounds with the therapeutic effect of the functionalizing agent. The R enantiomer of the 9-hydroxystearic acid, (9R)-9-HSA, produced from Dimorphotheca sinuata L. seeds, has proven to act as a natural negative regulator of tumor cell proliferation. On this basis, hydroxyapatite was synthesized with increasing contents of (9R)-9-hydroxystearate, up to â¼8.6 wt %. The incorporation of HSA in the composite nanocrystals induces a reduction of the crystal mean dimensions and of the length of the coherently scattering crystalline domains, which suggest a preferential adsorption onto the hydroxyapatite crystal faces parallel to the c-axis direction. The composite nanocrystals were designed so that their cytostatic and cytotoxic effects toward osteosarcoma cells were modulated by hydroxystearate content. In fact, results of in vitro tests show that the presence of HSA in the composite nanocrystals provokes a significant decrease in SaOS2 osteosarcoma cells proliferation and viability as well as an increase in lactate dehydrogenase, tumor necrosis factor α, and caspase 3 levels, with a cytotoxic effect increasing with HSA content in the nanocrystals.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Durapatite/chemistry , Stearic Acids/chemistry , Biocompatible Materials/chemistry , Cell Differentiation/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Nanoparticles/chemistryABSTRACT
Gelatin films are very versatile materials whose properties can be tuned through functionalization with different systems. This work investigates the influence of WO3 nanoparticles on the swelling, barrier, mechanical, and photochromic properties of gelatin films. To this purpose, polyvinylpirrolidone (PVP)-stabilized WO3 nanoparticles were loaded on gelatin films at two different pH values, namely, 4 and 7. The values of swelling and solubility of functionalized films displayed a reduction of around 50% in comparison to those of pristine, unloaded films. In agreement, WO3 nanoparticles provoked a significant decrease in water vapor permeability, whereas the decrease in the values of elastic modulus (from about 2.0 to 0.7 MPa) and stress at break (from about 2.5 to 1.4 MPa) can be ascribed to the discontinuity created by the nanoparticles inside the films. The results of differential scanning calorimetry and X-ray diffraction analysis suggest that interaction of PVP with gelatin reduce gelatin renaturation. No significant differences were found between the samples prepared at pH 4 and 7, whereas crosslinking with glutaraldehyde greatly influenced the properties of gelatin films. Moreover, the incorporation of WO3 nanoparticles in gelatin films, especially in the absence of glutaraldehyde, conferred excellent photochromic properties, inducing the appearance of an intense blue color after a few seconds of light irradiation and providing good resistance to several irradiation cycles.
ABSTRACT
Strontium, cobalt, and manganese ions are present in the composition of bone and useful for bone metabolism, even when combined with calcium phosphate in the composition of biomaterials. Herein we explored the possibility to include these ions in the composition of apatitic materials prepared through the cementitious reaction between ion-substituted calcium phosphate dibasic dihydrate, CaHPO4·2H2O (DCPD) and tetracalcium phosphate, Ca4(PO4)2O (TTCP). The results of the chemical, structural, morphological and mechanical characterization indicate that cobalt and manganese exhibit a greater delaying effect than strontium (about 15 at.%) on the cementitious reaction, even though they are present in smaller amounts within the materials (about 0.8 and 4.5 at.%, respectively). Furthermore, the presence of the foreign ions in the apatitic materials leads to a slight reduction of porosity and to enhancement of compressive strength. The results of biological tests show that the presence of strontium and manganese, as well as calcium, in the apatitic materials cultured in direct contact with human mesenchymal stem cells (hMSCs) stimulates their viability and activity. In contrast, the apatitic material containing cobalt exhibits a lower metabolic activity. All the materials have a positive effect on the expression of Vascular Endothelial Growth Factor (VEGF) and Von Willebrand Factor (vWF). Moreover, the apatitic material containing strontium induces the most significant reduction in the differentiation of preosteoclasts into osteoclasts, demonstrating not only osteogenic and angiogenic properties, but also ability to regulate bone resorption.
Subject(s)
Bone Regeneration , Cobalt , Manganese , Mesenchymal Stem Cells , Osteogenesis , Strontium , Strontium/pharmacology , Strontium/chemistry , Cobalt/chemistry , Humans , Osteogenesis/drug effects , Manganese/chemistry , Manganese/pharmacology , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Bone Regeneration/drug effects , Neovascularization, Physiologic/drug effects , Biocompatible Materials/pharmacology , Biocompatible Materials/chemistry , Vascular Endothelial Growth Factor A/metabolism , Calcium Phosphates/chemistry , Calcium Phosphates/pharmacology , Cell Survival/drug effects , AngiogenesisABSTRACT
This work investigated the range of substitution of two biologically relevant ions, namely Mn2+ and Co2+, into the structure of ß-tricalcium phosphate, as well as their influence on bone cells response. To this aim, ß-TCP was synthesized by solid state reaction in the presence of increasing amount of the substituent ions. The results of the X-ray diffraction analysis reveal that just limited amounts of these ions can enter into the ß-TCP structure: 15â¯at% and 20â¯at% for cobalt and manganese, respectively. Substitution provokes aggregation of the micrometric particles and reduction of the lattice constants. In particular, the dimension of the c-parameter exhibits a discontinuity at about 10â¯at% for both cations, although with different trend. Moreover, Rietveld refinement demonstrates a clear preference of both manganese and cobalt for the octahedral site (V). The influence of these ions on cell response was tested on osteoblast, osteoclast and endothelial cells. The results indicate that the presence of manganese promotes a good osteoblast viability, significantly enhances the expression of osteoblast key genes and the angiogenic process of endothelial cells, while inhibiting osteoclast resorption. At variance, osteoblast viability appears reduced in the presence of Co samples, on which osteoblast genes reach higher expression than on ß-TCP just in a few cases. On the other hand, the results clearly show that cobalt significantly stimulates the angiogenic process and inhibits osteoclast resorption.
ABSTRACT
In this paper the osteobiography of an elderly woman recovered from a cemetery tomb where she was buried in 1850, affected by hip fracture and osteoporosis, is described. The overall anthropological characteristics of the individual have been investigated. Macroscopic, radiographic, tomographic, microscopic, and chemical and structural examinations have been performed to give a detailed account of the condition of the skeleton. A non-union pertrochanteric fracture not surgically treated and probably due to senile osteoporosis was diagnosed. The consequences of the fracture to the bones show that this individual likely survived several years following the injury. The osseous features we describe (remodelled bone at the fracture site, asymmetry of entheseal changes likely related to the particular walking pattern of the individual) may be useful in personal identification of skeletons of legal interest. Regarding the recognition of osteoporosis in unearthed skeletons, our study underlines that the cortical thickness, microscopic features, degree of crystallinity and Ca/P ratio represent more useful elements than the mean bone density, mineral/matrix ratio and mineral maturity, which are more sensitive to diagenetic changes that affect the mineral phase post-mortem.
Subject(s)
Anthropology, Physical/methods , Hip Fractures/diagnosis , Osteoporosis/diagnosis , Acetabulum/diagnostic imaging , Acetabulum/injuries , Aged, 80 and over , Female , Hip Fractures/history , History, 19th Century , Humans , Interdisciplinary Communication , Osteoporosis/history , RadiographyABSTRACT
Curcumin has numerous biological activities and pharmaceutical applications related to its ability to inhibit reactive oxygen species. Herein, strontium-substituted monetite (SrDCPA) and strontium-substituted brushite (SrDCPD) were synthesized and further functionalized with curcumin with the aim to develop materials that combine the anti-oxidant properties of the polyphenol, the beneficial role of strontium toward bone tissue, and the bioactivity of calcium phosphates. Adsorption from hydroalcoholic solution increases with time and curcumin concentration, up to about 5-6 wt%, without affecting the crystal structure, morphology, and mechanical response of the substrates. The multi-functionalized substrates exhibit a relevant radical scavenging activity and a sustained release in phosphate buffer. Cell viability, morphology, and expression of the most representative genes were tested for osteoclast seeded in direct contact with the materials and for osteoblast/osteoclast co-cultures. The materials at relatively low curcumin content (2-3 wt%) maintain inhibitory effects on osteoclasts and support the colonization and viability of osteoblasts. The expressions of Alkaline Phosphatase (ALPL), collagen type I alpha 1 chain (COL1A1), and osteocalcin (BGLAP) suggest that curcumin reduces the osteoblast differentiation state but yields encouraging osteoprotegerin/receptor activator for the NFkB factor ligand (OPG/RANKL) ratio.
ABSTRACT
Reproducing in vitro a model of the bone microenvironment is a current need. Preclinical in vitro screening, drug discovery, as well as pathophysiology studies may benefit from in vitro three-dimensional (3D) bone models, which permit high-throughput screening, low costs, and high reproducibility, overcoming the limitations of the conventional two-dimensional cell cultures. In order to obtain these models, 3D bioprinting offers new perspectives by allowing a combination of advanced techniques and inks. In this context, we propose the use of hydroxyapatite nanoparticles, assimilated to the mineral component of bone, as a route to tune the printability and the characteristics of the scaffold and to guide cell behavior. To this aim, both stoichiometric and Sr-substituted hydroxyapatite nanocrystals are used, so as to obtain different particle shapes and solubility. Our findings show that the nanoparticles have the desired shape and composition and that they can be embedded in the inks without loss of cell viability. Both Sr-containing and stoichiometric hydroxyapatite crystals permit enhancing the printing fidelity of the scaffolds in a particle-dependent fashion and control the swelling behavior and ion release of the scaffolds. Once Saos-2 cells are encapsulated in the scaffolds, high cell viability is detected until late time points, with a good cellular distribution throughout the material. We also show that even minor modifications in the hydroxyapatite particle characteristics result in a significantly different behavior of the scaffolds. This indicates that the use of calcium phosphate nanocrystals and structural ion-substitution is a promising approach to tune the behavior of 3D bioprinted constructs.
ABSTRACT
Age-related musculoskeletal disorders, including osteoporosis, are frequent and associated with long lasting morbidity, in turn significantly impacting on healthcare system sustainability. There is therefore a compelling need to develop reliable preclinical models of disease and drug screening to validate novel drugs possibly on a personalized basis, without the need ofin vivoassay. In the context of bone tissue, although the osteocyte (Oc) network is a well-recognized therapeutic target, currentin vitropreclinical models are unable to mimic its physiologically relevant and highly complex structure. To this purpose, several features are needed, including an osteomimetic extracellular matrix, dynamic perfusion, and mechanical cues (e.g. shear stress) combined with a three-dimensional (3D) culture of Oc. Here we describe, for the first time, a high throughput microfluidic platform based on 96-miniaturized chips for large-scale preclinical evaluation to predict drug efficacy. We bioengineered a commercial microfluidic device that allows real-time visualization and equipped with multi-chips by the development and injection of a highly stiff bone-like 3D matrix, made of a blend of collagen-enriched natural hydrogels loaded with hydroxyapatite nanocrystals. The microchannel, filled with the ostemimetic matrix and Oc, is subjected to passive perfusion and shear stress. We used scanning electron microscopy for preliminary material characterization. Confocal microscopy and fluorescent microbeads were used after material injection into the microchannels to detect volume changes and the distribution of cell-sized objects within the hydrogel. The formation of a 3D dendritic network of Oc was monitored by measuring cell viability, evaluating phenotyping markers (connexin43, integrin alpha V/CD51, sclerostin), quantification of dendrites, and responsiveness to an anabolic drug. The platform is expected to accelerate the development of new drug aimed at modulating the survival and function of osteocytes.
Subject(s)
Bone and Bones , Osteocytes , Collagen/chemistry , Hydrogels , Lab-On-A-Chip DevicesABSTRACT
Calcium phosphate-based coatings are widely studied in orthopedics and dentistry for their similarity to the mineral component of bone and their capability to promote osseointegration. Different calcium phosphates have tunable properties that result in different behaviors in vitro, but the majority of studies focus only on hydroxyapatite. Here, different calcium phosphate-based nanostructured coatings are obtained by ionized jet deposition, starting with hydroxyapatite, brushite and beta-tricalcium phosphate targets. The properties of the coatings obtained from different precursors are systematically compared by assessing their composition, morphology, physical and mechanical properties, dissolution, and in vitro behavior. In addition, for the first time, depositions at high temperature are investigated for the further tuning of the coatings mechanical properties and stability. Results show that different phosphates can be deposited with good composition fidelity even if not in a crystalline phase. All coatings are nanostructured and non-cytotoxic and display variable surface roughness and wettability. Upon heating, higher adhesion and hydrophilicity are obtained as well as higher stability, resulting in better cell viability. Interestingly, different phosphates show very different in vitro behavior, with brushite being the most suitable for promoting cell viability and beta-tricalcium phosphate having a higher impact on cell morphology at the early timepoints.
ABSTRACT
BACKGROUND: Bacterial colonisation on implantable device surfaces is estimated to cause more than half of healthcare-associated infections. The application of inorganic coatings onto implantable devices limits/prevents microbial contaminations. However, reliable and high-throughput deposition technologies and experimental trials of metal coatings for biomedical applications are missing. Here, we propose the combination of the Ionized Jet Deposition (IJD) technology for metal-coating application, with the Calgary Biofilm Device (CBD) for high-throughput antibacterial and antibiofilm screening, to develop and screen novel metal-based coatings. RESULTS: The films are composed of nanosized spherical aggregates of metallic silver or zinc oxide with a homogeneous and highly rough surface topography. The antibacterial and antibiofilm activity of the coatings is related with the Gram staining, being Ag and Zn coatings more effective against gram-negative and gram-positive bacteria, respectively. The antibacterial/antibiofilm effect is proportional to the amount of metal deposited that influences the amount of metal ions released. The roughness also impacts the activity, mostly for Zn coatings. Antibiofilm properties are stronger on biofilms developing on the coating than on biofilms formed on uncoated substrates. This suggests a higher antibiofilm effect arising from the direct contact bacteria-coating than that associated with the metal ions release. Proof-of-concept of application to titanium alloys, representative of orthopaedic prostheses, confirmed the antibiofilm results, validating the approach. In addition, MTT tests show that the coatings are non-cytotoxic and ICP demonstrates that they have suitable release duration (> 7 days), suggesting the applicability of these new generation metal-based coatings for the functionalization of biomedical devices. CONCLUSIONS: The combination of the Calgary Biofilm Device with the Ionized Jet Deposition technology proved to be an innovative and powerful tool that allows to monitor both the metal ions release and the surface topography of the films, which makes it suitable for the study of the antibacterial and antibiofilm activity of nanostructured materials. The results obtained with the CBD were validated with coatings on titanium alloys and extended by also considering the anti-adhesion properties and biocompatibility. In view of upcoming application in orthopaedics, these evaluations would be useful for the development of materials with pleiotropic antimicrobial mechanisms.
ABSTRACT
This work describes a new one-step method for the preparation of AuNP/LDH nanocomposites via the polyol route. The novelty of this facile, simple synthesis is the absence of additional reactants such as reductive agents or stabilizer, which gives the possibility to obtain phase-pure systems free of undesiderable effect. The AuNP formation is confirmed by SEM, TEM, PXRD, and XAS; moreover, the electrochemical characterization is also reported. The electrocatalytic behavior of AuNP/LDH nanocomposites has been investigated with respect to the oxidation of methanol in basic media and compared with that of pristine NiAl-Ac. The 4-fold highest catalytic efficiency observed with AuNP/LDH nanocomposites suggests the presence of a synergic effect between Ni and AuNP sites. The combination of these experimental findings with the low-cost synthesis procedure paves the way for the exploitation of the presented nanocomposites materials as catalysts for methanol fuel cells.
Subject(s)
Electrochemical Techniques , Gold/chemistry , Hydroxides/chemistry , Metal Nanoparticles/chemistry , Methanol/chemistry , Catalysis , Oxidation-ReductionABSTRACT
Monetite and brushite are regarded with increasing interest for the preparation of biomaterials for applications in the musculoskeletal system. Herein, we investigated the influence of strontium substitution in the structures of these two phosphates on bone cell response. To achieve this aim, co-cultures of human primary osteoclasts and human osteoblast-like MG63 cells were tested on strontium-substituted monetite and strontium-substituted brushite, as well as on monetite and brushite, as controls. In both structures, strontium substitution for calcium amounted to about 6 at% and provoked enlargement of the cell parameters and morphologic variations. Cumulative release in physiological solution increased linearly over time and was greater from brushite (up to about 160 and 560 mg/L at 14 days for Sr and Ca, respectively) than from monetite (up to about 90 and 250 mg/L at 14 days for Sr and Ca, respectively). The increasing viability of osteoblast-like cells over time, with the different expression level of some typical bone markers, indicates a more pronounced trigger toward osteoblast differentiation and osteoclast inhibition by brushite materials. In particular, the inhibition of cathepsin K and tartrate-resistant acid phosphatase at the gene and morphological levels suggests strontium-substituted brushite can be applied in diseases characterized by excessive bone resorption.
ABSTRACT
The availability of biomaterials able to counteract bacterial colonization is one of the main requirements of functional implants and medical devices. Herein, we functionalized hydroxyapatite (HA) with tungsten oxide (WO3) nanoparticles in the aim to obtain composite materials with improved biological performance. To this purpose, we used HA, as well as HA functionalized with polyacrilic acid (HAPAA) or poly(ethylenimine) (HAPEI), as supports and polyvinylpyrrolidone (PVP) as stabilizing agent for WO3 nanoparticles. The number of nanoparticles loaded on the substrates was determined through Molecular Plasma-Atomic Emission Spectroscopy and is quite small, so it cannot be detected through X-ray diffraction analysis. It increases from HAPAA, to HA, to HAPEI, in agreement with the different values of zeta potential of the different substrates. HRTEM and STEM images show the dimensions of the nanoparticles are very small, less than 1 nm. In physiological solution HA support displays a greater tungsten cumulative release than HAPEI, despite its smaller loaded amount. Indeed, WO3 nanoparticles-functionalized HA exhibits a remarkable antibacterial activity against the Gram-positive Staphylococcus aureus in absence of cytotoxicity, which could be usefully exploited in the biomedical field.
ABSTRACT
The substitution of calcium with strontium in bioactive materials has been promising but there has been some concern over the material instability and possible toxicity. The aim of this research was the synthesis and characterization of calcium and strontium substituted bioactive materials and assessment of interactions with local tissues and peripheral elemental migration in an animal model. A bioactive glass, hydroxyapatite and hydraulic calcium silicate with 50% or 100% calcium substitution with strontium were developed and the set materials were characterized immediately after setting and after 30 and 180-days in solution. Following subcutaneous implantation, the local (tissue histology, elemental migration) and systemic effects (elemental deposition after organ digestion) were assessed. The strontium-replaced silicate cements resulted in the synthesis of partially substituted phases and strontium leaching at all-time points. The strontium silicate implanted in the animal model could not be retrieved in over half of the specimens showing the high rate of material digestion. Tissue histology showed that all materials caused inflammation after 30 days of implantation however this subsided and angiogenesis occurred after 180 days. Strontium was not detected in the local tissues or the peripheral organs while all calcium containing materials caused calcium deposition in the kidneys. The tricalcium silicate caused elemental migration of calcium and silicon in the local tissues shown by the elemental mapping but no deposition of calcium was identified in the peripheral organs verified by the assessment of the digested tissues. Strontium can substitute calcium in bioactive materials without adverse local or systemic effects.
Subject(s)
Calcium , Strontium , Calcium Compounds , Durapatite , Materials Testing , Silicates/pharmacology , Silicon , Strontium/pharmacologyABSTRACT
In this paper we used curcumin as a functionalizing agent of gelatin films with the aim to get antioxidant materials with modulated physico-chemical properties. To this aim, we prepared gelatin films at different contents of curcumin up to about 1.2 wt%. The as-prepared films, as well as glutaraldehyde crosslinked films, were submitted to several tests: swelling, water solubility, differential scanning calorimetry, X-ray diffraction, mechanical tests and curcumin release. The radical scavenging activity of the as-prepared films is similar to that of free curcumin, indicating remarkable antioxidant properties. All the other tested properties vary as a function of curcumin content and/or the presence of the crosslinking agent. In particular, the films exhibit sustained curcumin release in different solvents. Thanks to its biocompatibility, biodegradability and lack of antigenicity, gelatin uses span from food processing to packaging and biomaterials. It follows that the modulated properties exhibited by the functionalized materials developed in this work can be usefully employed in different application fields.
ABSTRACT
Multi-functionalization of calcium phosphates to get delivery systems of therapeutic agents is gaining increasing relevance for the development of functional biomaterials aimed to solve problems related to disorders of the muscolo-skeletal system. In this regard, we functionalized Strontium substituted hydroxyapatite (SrHA) with some ß-lactam integrin agonists to develop materials with enhanced properties in promoting cell adhesion and activation of intracellular signaling as well as in counteracting abnormal bone resorption. For this purpose, we selected two monocyclic ß-lactams on the basis of their activities towards specific integrins on promoting cell adhesion and signalling. The amount of ß-lactams loaded on SrHA could be modulated on changing the polarity of the loading solution, from 3.5-24 wt% for compound 1 and from 3.2-8.4 wt% for compound 2. Studies on the release of the ß-lactams from the functionalized SrHA in aqueous medium showed an initial burst followed by a steady-release that ensures a small but constant amount of the compounds over time. The new composites were fully characterized. Co-culture of human primary mesenchymal stem cells (hMSC) and human primary osteoclast (OC) demonstrated that the presence of ß-lactams on SrHA favors hMSC adhesion and viability, as well as differentiation towards osteoblastic lineage. Moreover, the ß-lactams were found to enhance the inhibitory role of Strontium on osteoclast viability and differentiation.
Subject(s)
Durapatite , beta-Lactams , Bone Regeneration , Cell Adhesion , Cell Differentiation , Humans , Hydroxyapatites , Integrins , Strontium/pharmacologyABSTRACT
A copper-based metal-organic framework (MOF) was prepared using a new linker, a 5-substituted isophthalic acid bearing a propargyl carbamate group, intended to provide a terminal alkyne function protruding from the material surface to generate supported gold species for potential catalytic applications. The novel material was fully characterized by spectroscopic analyses of different kinds: FTIR, Raman, EDX, and XPS, as well as by thermal and surface area measurements. Synchrotron X-ray diffraction data analysis, in particular, revealed that this MOF, labelled [Cu(1,3-YBDC)]·xH2O (x â¼ 2), where Y stands for the pendant alkYne and BDC for benzene dicarboxylate, contains a complex network of 5-substituted isophthalate anions bound to Cu(ii) centers, arranged in pairs within paddlewheel (or "Chinese lantern") fragments of Cu2(µ-COO)4(D)2 formulation (D being a neutral Lewis base), with a short Cuâ¯Cu distance of 2.633(4) Å. Quite unexpectedly, the apical atom in the paddlewheel structure belongs to the carbamate carbonyl oxygen atom. Such extra coordination by the propargyl carbamate groups drastically reduces the MOF porosity, a feature that was also confirmed by BET measurements. However, the MOF functionality is retained at the external crystal surface where 2% of active terminal alkynes is located.