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The bottom-up fabrication of supramolecular and self-assembly on various substrates has become an extremely relevant goal to achieve prospects in the development of nanodevices for electronic circuitry or sensors. One of the branches of this field is the self-assembly of functional molecular components driven through non-covalent interactions on the surfaces, such as van der Waals (vdW) interactions, hydrogen bonding (HB), electrostatic interactions, etc., allowing the controlled design of nanostructures that can satisfy the requirements of nanoengineering concepts. In this context, non-covalent interactions present opportunities that have been previously explored in several molecular systems adsorbed on surfaces, primarily due to their highly directional nature which facilitates the formation of well-ordered structures. Herein, we review a series of research works by combining STM (scanning tunneling microscopy) with theoretical calculations, to reveal the processes used in the area of self-assembly driven by molecule Landers equipped with functional groups on the metallic surfaces. Combining these processes is necessary for researchers to advance the self-assembly of supramolecular architectures driven by multiple non-covalent interactions on solid surfaces.
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Nanoestruturas , Propriedades de Superfície , Nanoestruturas/química , Microscopia de Tunelamento , Ligação de Hidrogênio , Eletricidade Estática , Adsorção , Nanotecnologia/métodosRESUMO
Different techniques have been developed to overcome the recalcitrant nature of lignocellulosic biomass and extract lignin biopolymer. Lignin has gained considerable interest owing to its attractive properties. These properties may be more beneficial when including lignin in the preparation of highly desired value-added products, including hydrogels. Lignin biopolymer, as one of the three major components of lignocellulosic biomaterials, has attracted significant interest in the biomedical field due to its biocompatibility, biodegradability, and antioxidant and antimicrobial activities. Its valorization by developing new hydrogels has increased in recent years. Furthermore, lignin-based hydrogels have shown great potential for various biomedical applications, and their copolymerization with other polymers and biopolymers further expands their possibilities. In this regard, lignin-based hydrogels can be synthesized by a variety of methods, including but not limited to interpenetrating polymer networks and polymerization, crosslinking copolymerization, crosslinking grafted lignin and monomers, atom transfer radical polymerization, and reversible addition-fragmentation transfer polymerization. As an example, the crosslinking mechanism of lignin-chitosan-poly(vinyl alcohol) (PVA) hydrogel involves active groups of lignin such as hydroxyl, carboxyl, and sulfonic groups that can form hydrogen bonds (with groups in the chemical structures of chitosan and/or PVA) and ionic bonds (with groups in the chemical structures of chitosan and/or PVA). The aim of this review paper is to provide a comprehensive overview of lignin-based hydrogels and their applications, focusing on the preparation and properties of lignin-based hydrogels and the biomedical applications of these hydrogels. In addition, we explore their potential in wound healing, drug delivery systems, and 3D bioprinting, showcasing the unique properties of lignin-based hydrogels that enable their successful utilization in these areas. Finally, we discuss future trends in the field and draw conclusions based on the findings presented.
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Quitosana , Lignina , Biomassa , Antioxidantes , Hidrogéis , PolímerosRESUMO
This patent review encapsulates information that could be used as a reference by researchers in the fields of coatings and interfaces, biofabrication, tissue engineering, biomaterials, and biomedical engineering, as well as those especially interested in the formulation of hydrogel coatings. The state has been reviewed by introducing what has been innovated, invented, and patented in relation to hydrogel coatings. A detailed analysis of the patentability of hydrogel applications, such as the coating of medical devices to enhance their clinical performance, has been provided. During a search, 2937 patent documents were found. 2012 was the year with the most patent documents (177). Based on the patent classification, all patent documents and most inventions are intended for biomaterials for coating prostheses characterized by their function or physical properties, such as macromolecular materials, hydrogels, and biologically active materials. Additionally, research based on medicinal formulations with unique physical forms is concentrated in the majority of patents, according to knowledge clusters and expert driving factors. Finally, to demonstrate the innovation trends in hydrogel-based coatings, a selection of relevant patent applications and granted patents is proposed at the end of this paper, along with some examples of commercial products based on the patented technologies.
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Materiais Biocompatíveis , Hidrogéis , Próteses e Implantes , Engenharia TecidualRESUMO
Polysaccharides have found extensive utilization as biomaterials in drug delivery systems owing to their remarkable biocompatibility, simple functionalization, and inherent biological properties. Within the array of polysaccharide-based biomaterials, there is a growing fascination for self-assembled polysaccharide nanogels (NG) due to their ease of preparation and enhanced appeal across diverse biomedical appliances. Nanogel (or nanohydrogel), networks of nanoscale dimensions, are created by physically or chemically linking polymers together and have garnered immense interest as potential carriers for delivering drugs due to their favorable attributes. These include biocompatibility, high stability, the ability to adjust particle size, the capacity to load drugs, and their inherent potential to modify their surface to actively target specific cells or tissues via the attachment of ligands that can recognize corresponding receptors. Nanogels can be engineered to respond to specific stimuli, such as pH, temperature, light, or redox conditions, allowing controlled release of the encapsulated drugs. This intelligent targeting capability helps prevent drug accumulation in unintended tissues and reduces the potential side effects. Herein, an overview of nanogels is offered, comprising their methods of preparation and the design of stimulus-responsive nanogels that enable controlled release of drugs in response to specific stimuli.
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Sistemas de Liberação de Medicamentos , Polissacarídeos , Nanogéis/química , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos/métodos , Materiais BiocompatíveisRESUMO
PURPOSE: To investigate whether embolization with chitosan hydrogel (CH) with or without a sclerosant (sodium tetradecyl sulphate, STS) can induce chemical endothelial ablation and prevent endothelial recanalization in a rabbit model. METHODS: Chitosan radiopaque thermogels were prepared using chitosan, ß-glycerophosphate, iopamidol, and different STS concentrations. Each auricular artery of 14 New Zealand White rabbits was cannulated and injected with 0.6 mL of chitosan (CH0; nâ=â14) on one side and either saline (nâ=â3), chitosan and 1% STS (CH1; nâ=â6), or chitosan and 3% STS (CH3; nâ=â6) in the contralateral side. Immediately after embolization and at 1, 7, 14, and 30 days, auricular artery patency and percentage of recanalization were assessed by visual inspection; microcirculation was evaluated using laser Doppler imaging (LDI). The rabbits were sacrificed at 30 days to assess endothelial ablation and inflammatory response by histological analyses. RESULTS: All arteries were catheterized and embolized with success. All saline-injected arteries rapidly recovered normal flow. The length of embolization was greater with CH3 than CH1 or CH0, regardless of the time observed (p<0.001). No difference in recanalization length was found among the gels (pâ=â0.07). Destruction of arterial wall was frequently observed independent of embolizing agent. Foreign body reaction was more frequent with CH3 as compared with CH1 and CH0 (pâ=â0.0070 and 0.0058, respectively). After 30 days, hypervascularization was observed on LDI only with CH0; it was attributed to intra- or perivascular neovessels and inflammatory response on pathological analysis. The vascular modifications appeared to be more homogenous across the length of embolization with CH3 than the other formulations. CONCLUSION: The viscosity obtained with chitosan and 3% STS permits better control during injection and longer vascular occlusion. These findings, combined with the intravascular neovascularization observed with CH0, led us to prefer the combination with STS.
Assuntos
Técnicas de Ablação , Quitosana/administração & dosagem , Orelha/irrigação sanguínea , Embolização Terapêutica/métodos , Células Endoteliais/efeitos dos fármacos , Soluções Esclerosantes/administração & dosagem , Tetradecilsulfato de Sódio/administração & dosagem , Técnicas de Ablação/efeitos adversos , Animais , Artérias/efeitos dos fármacos , Artérias/patologia , Artérias/fisiopatologia , Quitosana/efeitos adversos , Relação Dose-Resposta a Droga , Embolização Terapêutica/efeitos adversos , Células Endoteliais/patologia , Reação a Corpo Estranho/etiologia , Reação a Corpo Estranho/patologia , Hidrogéis , Injeções Intra-Arteriais , Fluxometria por Laser-Doppler , Microcirculação , Modelos Animais , Neovascularização Patológica , Coelhos , Fluxo Sanguíneo Regional , Soluções Esclerosantes/efeitos adversos , Tetradecilsulfato de Sódio/efeitos adversos , Fatores de Tempo , Grau de Desobstrução Vascular , ViscosidadeRESUMO
Calcium phosphate ceramics suspensions (ICPCS) are used in bone and dental surgery as injectable bone substitutes. This ICPCS biomaterial associates biphasic calcium phosphate (BCP) granules with hydroxypropylmethylcellulose (HPMC) polymer. Different ICPCS were prepared and their rheological properties were evaluated in parallel disks geometry as a function of the BCP weight ratio (35, 40, 45 and 50 %). The suspensions show a strongly increased viscosity as compared to the suspending fluid and the high shear rate part of the flow curve can be fitted with a power law model (Ostwald-de Waele model). The fitting parameters depend on the composition of the suspension. A simple device has been used to characterize extrusion of the paste using a disposable syringe fitted with a needle. The injection pressure of four ICPCS formulations was studied under various conditions (needle length and radius and volumetric flow rate), yielding an important set of data. A theoretical approach based on the capillary flow of non-Newtonian fluids was used to predict the necessary pressure for injection, on the basis of flow curves and extrusion conditions. The extrusion pressure calculated from rheological data shows a quantitative agreement with the experimental one for model fluids (Newtonian and HPMC solution) but also for the suspension, when needles with sufficiently large diameters as compared to the size of particles, are used. Depletion and possibly wall slip is encountered in the suspensions when narrower diameters are used, so that the injection pressure is less than that anticipated. However a constant proportionality factor exists between theory and injection experiments. The approach developed in this study can be used to correlate the rheological parameters to the necessary pressure for injection and defines the pertinent experimental conditions to obtain a quantitative agreement between theory and experiments.
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Fosfatos de Cálcio , Pomadas , Materiais Biocompatíveis , Derivados da Hipromelose , Metilcelulose/análogos & derivados , Microscopia Eletrônica de Varredura , ReologiaRESUMO
BACKGROUND: Biological control (i.e., biocontrol) can be defined as the use of microbial inoculants with a direct and purposeful manipulation of natural enemies, potentially replacing harmful pesticides, to control pests, plant pathogens, and weeds. This study concerns patent analysis of biocontrol agent-based formulations. This form of patent analysis encapsulates information that could be used as a reference by researchers in the fields of agriculture and plants, as well as those interested, especially in biocontrol agents for agriculture. METHODS: The state has been reviewed by introducing what has been patented concerning Biocontrol Agents (BCAs). Four patent databases have been used, and different keywords and related terms to BCAs were used, and patents were searched according to title, abstract, and claims. The search was then filtered regarding publication year, patent families, patent classifications, inventors, applicants, owners, and jurisdictions. RESULTS: During a search, 2371 patent documents were found between 1982 and 2021. The United States was ranked first with 694 patent documents. 2015 was the year with the maximum number of patent documents (278). The patent classification codes reveal that most inventions are intended for biocides, pest repellants or attractants, or plant growth regulators containing or obtained from microorganisms, viruses, microbial fungi, etc. Moreover, they are also intended for biocidal, pest repellant, pest attractant, or plant growth regulatory activities of chemical compounds or preparations, such as fungicides, athropodicides, and nematocides, which are concentrated in most patents. CONCLUSION: The knowledge clusters and expert driving factors of this patent analysis indicate that the research and development based on the formulation of biocontrol agents are concentrated in most patents.
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Agentes de Controle Biológico , Praguicidas , Humanos , Estados Unidos , Agentes de Controle Biológico/farmacologia , Agricultura , Praguicidas/farmacologia , Invenções , Plantas DaninhasRESUMO
BACKGROUND: This paper provides a comprehensive overview of the patent situation for hydrogel- based bioinks used for 3D bioprinting globally. It encapsulates information which could be used as a reference by researchers in the fields of 3D bioprinting, biomaterials, tissue engineering, and biomedical engineering, as well as those interested in biomaterials, especially in the formulation of hydrogels. It can also inform policy discussions, strategic research planning, or technology transfer in this area. The findings presented hereinafter are considered novel research aspects regarding the used hydrogels, their preparation methods, and their formulations, as well as the 3D bioprinting process using hydrogels. Furthermore, the novel part, synthesized patents, is regarded as a breakthrough in hydrogel- based bioinks. METHODS: The following research aspects of this study are based on data collection from selected patent databases. The search results are then analyzed according to publication years, classification, inventors, applicants, and owners, as well as jurisdictions. RESULTS: Based on the earliest priority date, it is possible to precisely assume that 2004 is considered the starting year of patenting of hydrogel-based bioinks. Furthermore, 2020 was the year with the most patent documents. According to the findings, the United States, China, and the Republic of Korea are the most prolific countries in terms of patenting on hydrogel-based bioinks. The most prolific patenting companies are from the United States, Sweden, and Australia, while universities from the Republic of Korea and the United States are the academic institutions leading the way. Most inventions of hydrogel- based bioinks intended for hydrogels or hydrocolloids used as materials for prostheses or for coating prostheses are characterized by their function or physical properties. CONCLUSION: The state has been reviewed by introducing what has been patented concerning hydrogelbased bioinks. Knowledge clusters and expert driving factors indicate that the research based on biomaterials, tissue engineering, and biofabrication is concentrated in the most common patent documents. Finally, this paper, which gives a competitive analysis of the past, present, and future trends in hydrogel-based bioinks, leads to various recommendations that could help one to plan and innovate research strategies.
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Bioimpressão , Bioimpressão/métodos , Hidrogéis , Impressão Tridimensional , Engenharia Tecidual/métodos , Materiais Biocompatíveis/uso terapêuticoRESUMO
BACKGROUND: Seaweed-based biofertilizers for agriculture are developing rapidly through the innovation and improvement of used raw materials, formulations, methods, and processes. This is evident from the increase in the number of patent applications filed each year in this area of seaweed-based biofertilizer research and development. METHODS: This study concerns the patentability and patent analysis of seaweed-based biofertilizers between 2000 and 2020. This form of patent analysis englobes information that could be used as a reference by researchers in the fields of agriculture, as well as those interested, especially in biofertilizers. During a search, different keywords and related terms were used, and patents were searched according to title, abstract, and claims. A detailed analysis was then given regarding publication year, patent classifications, inventors, applicants, owners, and jurisdictions. Finally, innovation and improvement of seaweed-based biofertilizers are proposed. RESULTS: 1731 patent documents have been found. The analyzed period confirms that China was ranked first with 1336 patent documents, and 2017 was the year with the maximum number of patent documents (288). CONCLUSION: The patent classification codes reveal that most of the inventions are intended for soil conditioners and preparation of fertilizers characterized by biological or biochemical treatment steps, as well as organic fertilizers containing added bacterial cultures.
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Fertilizantes , Alga Marinha , Agricultura , Invenções , Patentes como Assunto , VerdurasRESUMO
Three-dimensional (3D) printing is well acknowledged to constitute an important technology in tissue engineering, largely due to the increasing global demand for organ replacement and tissue regeneration. In 3D bioprinting, which is a step ahead of 3D biomaterial printing, the ink employed is impregnated with cells, without compromising ink printability. This allows for immediate scaffold cellularization and generation of complex structures. The use of cell-laden inks or bio-inks provides the opportunity for enhanced cell differentiation for organ fabrication and regeneration. Recognizing the importance of such bio-inks, the current study comprehensively explores the state of the art of the utilization of bio-inks based on natural polymers (biopolymers), such as cellulose, agarose, alginate, decellularized matrix, in 3D bioprinting. Discussions regarding progress in bioprinting, techniques and approaches employed in the bioprinting of natural polymers, and limitations and prospects concerning future trends in human-scale tissue and organ fabrication are also presented.
RESUMO
Alginates are widely used polysaccharides for biomaterials engineering, which functional properties depend on guluronic and mannuronic acid as the building blocks. In this study, enzymatically crosslinked hydrogels based on sodium alginate (Na-Alg) and the exopolysaccharide (EPS) derived from Cryptococcus laurentii 70766 with glucuronic acid residues were synthesized and characterized as a new potential source of polysaccharide for biomaterials engineering. The EPS was extracted (1.05 ± 0.57 g/L) through ethanol precipitation. Then the EPS and Na-Alg were functionalized with tyramine hydrochloride to produce enzymatically crosslinked hydrogels in the presence of horseradish peroxidase (HRP) and H2O2. Major characteristics of the hydrogels such as gelling time, swelling ratio, rheology, cell viability, and biodegradability were studied. The swelling ratio and degradation profile of both hydrogels showed negative values, indicating an increased crosslinking degree and a lower water uptake percentage. The EPS hydrogel showed similar gelation kinetics compared to the Alg hydrogel. The EPS and its hydrogel were found cytocompatible. The results indicate the potential of EPS from C. laurentii 70766 for biomedical engineering due to its biocompatibility and degradability. Further studies are needed to confirm this EPS as an alternative for Alg in tissue engineering applications, particularly in the development of wound dressing products.
Assuntos
Alginatos , Hidrogéis , Alginatos/química , Basidiomycota , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Hidrogéis/química , Peróxido de Hidrogênio/química , Íons , Engenharia Tecidual/métodosRESUMO
Polysaccharides are highly heat-sensitive macromolecules, so high temperature treatments are greatly destructive and cause considerable damage, such as a great decrease in both viscosity and molecular weight of the polymer. The technical feasibility of the production of exopolysaccharides by deep-sea bacteria Vibrio diabolicus and Alteromonas infernus was previously demonstrated using a bioproduct manufacturing process. The objective of this study was to determine which sterilization method, other than heat sterilization, was the most appropriate for these marine exopolysaccharides and was in accordance with bioprocess engineering requirements. Chemical sterilization using low-temperature ethylene oxide and a mixture of ionized gases (plasmas) was compared to the sterilization methods using gamma and beta radiations. The changes to both the physical and chemical properties of the sterilized exopolysaccharides were analyzed. The use of ethylene oxide can be recommended for the sterilization of polysaccharides as a weak effect on both rheological and structural properties was observed. This low-temperature gas sterilizing process is very efficient, giving a good Sterility Assurance Level (SAL), and is also well suited to large-scale compound manufacturing in the pharmaceutical industry.
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Alteromonas/química , Polissacarídeos Bacterianos/química , Esterilização/métodos , Vibrio/química , Animais , Partículas beta , Produtos Biológicos/química , Sequência de Carboidratos , Óxido de Etileno/química , Óxido de Etileno/toxicidade , Raios gama , Temperatura Alta , Dados de Sequência Molecular , Peso Molecular , Oceanos e Mares , Gases em Plasma/química , Polissacarídeos Bacterianos/isolamento & purificação , Polissacarídeos Bacterianos/efeitos da radiação , Polissacarídeos Bacterianos/toxicidade , Coelhos , Espectroscopia de Infravermelho com Transformada de Fourier , ViscosidadeRESUMO
Calcium phosphate ceramics are widely used as bone substitutes in dentistry and orthopedic applications. For minimally invasive surgery an injectable calcium phosphate ceramic suspension (ICPCS) was developed. It consists in a biopolymer (hydroxypropylmethylcellulose: HPMC) as matrix and bioactive calcium phosphate ceramics (biphasic calcium phosphate: BCP) as fillers. The stability of the suspension is essential to this generation of "ready to use" injectable biomaterial. But, during storage, the particles settle down. The engineering sciences have long been interested in models describing the settling (or sedimentation) of particles in viscous fluids. Our work is dedicated to the comprehension of the effect of the formulation on the stability of calcium phosphate suspension before and after steam sterilization. The rheological characterization revealed the macromolecular behavior of the suspending medium. The investigations of settling kinetics showed the influence of the BCP particle size and the HPMC concentration on the settling velocity and sediment compactness before and after sterilization. To decrease the sedimentation process, the granule size has to be smaller and the polymer concentration has to increase. A much lower sedimentation velocity, as compared to Stokes law, is observed and interpreted in terms of interactions between the polymer network in solution and the particles. This experimentation highlights the granules spacer property of hydrophilic macromolecules that is a key issue for interconnection control, one of the better ways to improve osteoconduction and bioactivity.
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Fosfatos de Cálcio/farmacologia , Materiais Biocompatíveis/farmacologia , Substitutos Ósseos/farmacologia , Cerâmica/farmacologia , Derivados da Hipromelose , Injeções , Metilcelulose/análogos & derivados , Tamanho da Partícula , Polímeros/farmacologia , Reologia , ViscosidadeRESUMO
This paper describes the rheological properties of silated hydroxypropylmethylcellulose (HPMC-Si) used in biomaterials domain as a three-dimensional synthetic matrix for tissue engineering. The HPMC-Si is an HPMC grafted with 3-glycidoxypropyltrimethoxysilane (GPTMS). HPMC and HPMC-Si were studied. It is shown that although silanization reduces the hydrodynamic volume in dilute solution, it does not affect significantly the rheological behavior of the concentrated solutions. The HPMC-Si viscous solution (pH 12.8) cross-links by decreasing the pH using an acid buffer, since HPMC-Si solution transforms into an elastic state. The kinetics of cross-linking and final elastic properties is influenced by several parameters such as polymer concentration, pH and temperature. pH and temperature play an important role in the silanol condensation, mainly responsible for network formation. The study of the gelation process revealed the dependence of the final concentration of HPMC-Si hydrogel on cross-linking kinetics and viscoelastic properties. The percolation theory was applied to determine gel point and to discuss the dependence of storage (G') and loss (G'') moduli on frequency. Results showed that both G' and G'' exhibit a power-law behavior with an exponent (0.68) which extends over the entire frequency range. This method is the only one to characterize the time where a liquid viscous phase shifts to hydrogel with elastic properties. In this case it was about 23 min for a final pH of 7.4.
Assuntos
Metilcelulose/análogos & derivados , Dióxido de Silício/química , Engenharia Tecidual , Elasticidade , Derivados da Hipromelose , Metilcelulose/química , Estrutura Molecular , Reologia , Soluções , Espectroscopia de Infravermelho com Transformada de Fourier , Fatores de Tempo , ViscosidadeRESUMO
PURPOSE: To compare the efficacy of an embolization agent with sclerosing properties (made of chitosan and sodium tetradecyl sulfate, CH-STS) with a similar embolization agent but without sclerosing properties (made of chitosan, CH) in treating endoleaks in a canine endovascular aneurysm repair model. METHODS: Two chitosan-based radiopaque hydrogels were prepared, one with STS and one without STS. Their rheological, injectability, and embolizing properties were assessed in vitro; afterwards, their efficacy in occluding endoleaks was compared in a canine bilateral aneurysm model reproducing type I endoleaks (n = 9 each). The primary endpoint was endoleak persistence at 3 or 6 months, assessed on a CT scan and macroscopic examination. Secondary endpoints were the occurrence of stent-graft (SG) thrombosis, the evolution of the aneurysm mean diameter, as well as aneurysm healing and inflammation scores in pathology examinations. RESULTS: In vitro experiments showed that both products gelled rapidly and presented initial storage moduli greater than 800 Pa, which increased with time. Both gels were compatible with microcatheter injection and occlude flow up to physiological pressure in vitro. In a type I endoleak model, the injection of CH-STS sclerosing gel tended to reduce the risk of occurrence of endoleaks, compared to CH non-sclerosing agent (2/9 vs. 6/9, p = 0.069). No case of SG thrombosis was observed. Moderate inflammation was found around both gels, with a comparable intensity score in both CH and CH-STS groups (2.6 ± 0.9 and 2.7 ± 0.9, respectively; p = 0.789). CONCLUSIONS: Flow occlusion combined with chemical endothelial denudation appears promising for the treatment of endoleaks. LEVEL OF EVIDENCE: N/A.
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Quitosana/administração & dosagem , Embolização Terapêutica/métodos , Endoleak/terapia , Hidrogéis/administração & dosagem , Soluções Esclerosantes/administração & dosagem , Tetradecilsulfato de Sódio/administração & dosagem , Animais , Modelos Animais de Doenças , Cães , Procedimentos Endovasculares/métodosRESUMO
Chitosan-thermosensitive hydrogels present interesting features for the embolization of blood vessels, but need to be better characterized and optimized. Chitosan polymer (degree of deacetylation (DDA) of 94%) was purified and combined with Visipaque (VIS), a nonionic isotonic contrast agent composed of iodixanol. A beta-glycerolphosphate (ßGP) solution was then added to induce gelation at body temperature. The gelation process was monitored by rheometry, measuring the evolution of the sample storage (G') and loss (Gâ³) moduli as a function of VIS and ßGP concentration. Adding VIS significantly slowed down gelation kinetics, but a 12% and higher ßGP concentration provided a radiopaque solution, which at 37°C, gels immediately. A custom-made in vitro embolization bench test was developed to assess the gel's occlusive properties, and its injectability through a small diameter catheter was verified. Results show that the short-term occlusive properties of the gel were insufficient when using a ßGP concentration of 12% w/v (about 0.4M), but that increasing the ßGP to 20% (0.6M) allowed an acceleration of the gelation and the immediate blocking of flow above physiological pressure. The contrast agent was rapidly released in solution, such that it would not interfere with future follow-up imaging. In accordance with the literature data, the cytotoxicity of gel extracts increased with ßGP concentration and to a lesser extent with VIS concentration. Preliminary in vivo testing showed easy injection by catheter and good visibility under fluoroscopy. These results suggest that radiopaque CH/ßGP20%/VIS hydrogels present significant potential as embolizing agents for blood vessels and aneurysms. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1551-1562, 2016.
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Quitosana , Embolização Terapêutica/métodos , Hidrogéis , Ácidos Tri-Iodobenzoicos , Animais , Linhagem Celular , Quitosana/química , Quitosana/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Ácidos Tri-Iodobenzoicos/química , Ácidos Tri-Iodobenzoicos/farmacologiaRESUMO
A new injectable radiopaque embolizing agent has been developed, based on chitosan thermogelling properties. Different commercial contrast agents (Isovue®, Visipaque®, and Conray®) were associated with chitosan-ß-glycerophosphate. Their impact on gelation kinetic, mechanical properties, radiopacity, and cytotoxicity was tested to evaluate the best candidate and its feasibility for the treatment of endoleaks after endovascular aneurysm repair (EVAR). Addition of contrast agents did not prevent gelation at body temperature, but it significantly increased the viscosity of the solution before gelation, delayed gelation, and reduced the gelation rate. However, using chitosan with a high degree of deacetylation and 20 vol % contrast agent made it possible to obtain a gel with rapid gelation that was visible during X-ray based guided intervention. Hydrogels exhibit relatively low mechanical properties, which are only slightly modified by the addition of contrast agents. In vitro studies have demonstrated rapid release of contrast agents from hydrogels when immersed in a saline solution (>50% within 4 h). This is suitable for embolization, as radiopacity is required only to follow the embolization procedure, while long-term radiopacity would hamper further imaging and endoleak detection. Cytotoxicity and osmolality testing of extracts demonstrated some toxicity of products released by the gel during the first few hours, which is mainly related to their hypertonicity. After the first 24 h incubation, hydrogels released no more cytotoxic compounds, suggesting that the hydrogel rapidly becomes biocompatible. Altogether, this study suggests that the new radiopaque thermogels present interesting characteristics as embolizing agents for EVAR, although their mechanical properties require improvement.
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Aneurisma/cirurgia , Quitosana/química , Meios de Contraste , Embolização Terapêutica , Géis , Animais , Linhagem Celular , Sobrevivência Celular , Camundongos , Concentração Osmolar , ReologiaRESUMO
Endovascular repair of abdominal aortic aneurysms with a stent graft is limited by the persistence or recurrence of endoleaks. These are believed to be related to the recanalization of the aneurismal sac by endothelialized neochannels, which could lead to late type I and II endoleaks. Embolization has been proposed to treat or prevent endoleaks, but presently commercialized embolizing materials have several drawbacks and do not fully prevent endoleak recurrence. A novel chitosan hydrogel that is injectable, radiopaque and contains sodium tetradecyl sulfate (STS), a well-known sclerosing agent, was developed in order to combine blood flow occlusion and endothelium ablation properties. chitosan/STS hydrogels were characterized and optimized using rheometry, scanning electron microscopy, swelling and ex vivo embolization assay. They were shown to exhibit rapid gelation and good mechanical properties, as well as sclerosing properties. Their potential for the embolization of aneurysms was subjected to preliminary in vivo evaluation in a bilateral iliac aneurysm model (three dogs) reproducing persistent endoleaks after endovascular aneurysm repair (EVAR). At 3 months no endoleak was detected in any of the three aneurysms treated with chitosan/STS hydrogels. In contrast, type I endoleaks were detected in two of the three aneurysms treated with chitosan hydrogels. Generally, chitosan/STS hydrogels have great potential as embolizing and sclerosing agents for EVAR and possibly other endovascular therapies.
Assuntos
Quitosana/química , Meios de Contraste/farmacologia , Embolização Terapêutica , Procedimentos Endovasculares/métodos , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Aneurisma Ilíaco/terapia , Soluções Esclerosantes/farmacologia , Animais , Meios de Contraste/administração & dosagem , Modelos Animais de Doenças , Cães , Módulo de Elasticidade/efeitos dos fármacos , Fator VIII/metabolismo , Hidrogel de Polietilenoglicol-Dimetacrilato/administração & dosagem , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Técnicas In Vitro , Injeções , Microscopia Eletrônica de Varredura , Reologia , Soluções Esclerosantes/administração & dosagem , Tetradecilsulfato de Sódio/administração & dosagem , Tetradecilsulfato de Sódio/química , Tetradecilsulfato de Sódio/farmacologia , Fatores de TempoRESUMO
The present paper investigates the rheological properties of silated hydroxypropylmethylcellulose (Si-HPMC) biohydrogel used for biomaterials and tissue engineering applications. The general property of this modified cellulose ether is the occurrence of self-hardening due to silanol condensation subsequent to a decrease in pH (from 12.4 to nearly 7.4). The behavior of unsterilized and sterilized Si-HPMC solutions in diluted and concentrated domains is first described and compared. In addition, the influence of physiological parameters such as pH and temperature on the rate of the gelation process is studied. In dilute solution, the intrinsic viscosity ([eta]) of different pre-steam sterilization Si-HPMC solutions indicates that macromolecular chains occupy a larger hydrodynamic volume than the post-steam sterilization Si-HPMC solutions. Although the unsterilized Si-HPMC solutions demonstrate no detectable influence of pH upon the rheological behavior, a decrease in the limiting viscosities (eta(0)) of solutions with increasing pH is observed following steam sterilization. This effect can be explained by the formation of intra- and intermolecular associations during the sterilization stage originating from the temperature-induced phase separation. The formation of Si-HPMC hydrogels from injectable aqueous solution is studied after neutralization by different acid buffers leading to various final pHs. Gelation time (t(gel)) decreases when pH increases (t(gel) varies from 872 to 11s at pH 7.4 and 11.8, respectively). The same effect is observed by increasing the temperature from 20 to 45 degrees C. This is a consequence of the synergistic effect of the increased reaction rate and acid buffer diffusion. pH and temperature are important parameters in the gelation process and their influence is a key factor in controlling gelation time. By adapting the gel parameters one could propose hydrogels with cross-linking properties adapted to clinical applications by controlling the amount of pH of neutralization and temperature.
Assuntos
Celulose/química , Hidrogéis/química , Concentração de Íons de Hidrogênio , Teste de Materiais , Estrutura Molecular , Transição de Fase , Reologia , Esterilização , Temperatura , Termodinâmica , ViscosidadeRESUMO
In this paper we report a new method that permitted for the first time to selectively track a polysaccharide-based hydrogel on bone tissue explants, several weeks after its implantation. The hydrogel, which was developed for bone healing and tissue engineering, was labelled with a ruthenium complex and implanted into rabbit bone defects in order to investigate its in vivo degradation. 1, 2, 3 and 8 weeks after surgery, the bone explants were analyzed by synchrotron X-ray microfluorescence, infrared mapping spectroscopy, scanning electron microscopy, and optical microscopy after histological coloration. The results showed that the labelled polysaccharide-based hydrogel was likely to undergo phagocytosis that seemed to occur from the edge to the center of the implantation site up to at least the 8th week.