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Spinal cord injuries (SCI) have devastating physical, psychological, and psychosocial consequences for patients. One challenge of nerve tissue repair is the lack of a natural extracellular matrix (ECM) that guides the regenerating axons. Hyaluronic acid (HA) is a major ECM component and plays a fundamental role in facilitating lesion healing. Herein, we developed HA-based adhesive hydrogels by modification of HA with dopamine, a mussel-inspired compound with excellent adhesive properties in an aqueous environment. The hydrogels were loaded with the anti-inflammatory drug ibuprofen and the response of neuronal cells (SH-SY5Y) was evaluated in terms of viability, morphology, and adhesion. The obtained results suggested that the developed materials can bridge lesion gaps, guide axonal growth, and simultaneously act as a vehicle for the delivery of bioactive compounds.
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Neuroblastoma , Traumatismos de la Médula Espinal , Humanos , Ácido Hialurónico , Hidrogeles , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/patología , Neuronas/patología , Médula Espinal/patologíaRESUMEN
Ligaments and tendons are fibrous tissues with poor vascularity and limited regeneration capacity. Currently, a ligament/tendon injury often require a surgical procedure using auto- or allografts that present some limitations. These inadequacies combined with the significant economic and health impact have prompted the development of tissue engineering approaches. Several natural and synthetic biodegradable polymers as well as composites, blends and hybrids based on such materials have been used to produce tendon and ligament scaffolds. Given the complex structure of native tissues, the production of fiber-based scaffolds has been the preferred option for tendon/ligament tissue engineering. Electrospinning and several textile methods such as twisting, braiding and knitting have been used to produce these scaffolds. This review focuses on the developments achieved in the preparation of tendon/ligament scaffolds based on different biodegradable polymers. Several examples are overviewed and their processing methodologies, as well as their biological and mechanical performances, are discussed.
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Materiales Biocompatibles/química , Ligamentos/cirugía , Nanocompuestos/química , Polímeros/química , Tendones/cirugía , Andamios del Tejido/química , Animales , Productos Biológicos/química , Fenómenos Biomecánicos , Adhesión Celular , Línea Celular , Proliferación Celular , Humanos , Regeneración , Relación Estructura-Actividad , Propiedades de Superficie , Ingeniería de TejidosRESUMEN
The authors wish to make changes to the published paper [...].
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Freestanding films based on catechol functionalized chitosan (CHI), hyaluronic acid (HA), and bioglass nanoparticles (BGNPs) were developed by spin-coating layer-by-layer assembly (SA-LbL). The catechol groups of 3,4-dihydroxy-l-phenylalanine (DOPA) present in the marine mussels adhesive proteins (MAPs) are the main factors responsible for their characteristic strong wet adhesion. Then, the produced films were cross-linked with genipin to improve their stability in wet state. Overall, the incorporation of BGNPs resulted in thicker and bioactive films, hydrophilic and rougher surfaces, reduced swelling, higher weight loss, and lower stiffness. The incorporation of catechol groups onto the films showed a significant increase in the films' adhesion and stiffness, lower swelling, and weight loss. Interestingly, a synergetic effect on the stiffness increase was observed upon the combined incorporation of BGNPs with catechol-modified polymers, given that such films were the stiffest. Regarding the biological assays, the films exhibited no negative effects on cellular viability, adhesion, and proliferation, and the BGNPs seemed to promote higher cellular metabolic activity. These bioactive LbL freestanding films combine enhanced adhesion with improved mechanical properties and could find applications in the biomedical field, such as guided hard tissue regeneration membranes.
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Materiales Biomiméticos/química , Materiales Biocompatibles Revestidos/química , Nanopartículas/química , Polisacáridos/farmacología , Adhesivos/química , Adhesivos/farmacología , Catecoles/química , Adhesión Celular/efectos de los fármacos , Cerámica/química , Quitosano/química , Materiales Biocompatibles Revestidos/farmacología , Ácido Hialurónico/química , Ensayo de Materiales , Membranas Artificiales , Polímeros/química , Polisacáridos/química , Proteínas/químicaRESUMEN
Inspired by nature, in particular by the marine mussels adhesive proteins (MAPs) and by the tough brick-and-mortar nacre-like structure, novel multilayered films are prepared in the present work. Organic-inorganic multilayered films, with an architecture similar to nacre based on bioactive glass nanoparticles (BG), chitosan, and hyaluronic acid modified with catechol groups, which are the main components responsible for the outstanding adhesion in MAPs, are developed for the first time. The biomimetic conjugate is prepared by carbodiimide chemistry and analyzed by ultraviolet-visible spectrophotometry. The buildup of the multilayered films is monitored with a quartz crystal microbalance with dissipation monitoring, and their topography is characterized by atomic force microscopy. The mechanical properties reveal that the films containing catechol groups and BG present an enhanced adhesion. Moreover, the bioactivity of the films upon immersion in a simulated body fluid solution is evaluated by scanning electron microscopy coupled with energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. It was found that the constructed films promote the formation of bonelike apatite in vitro. Such multifunctional mussel inspired LbL films, which combine enhanced adhesion and bioactivity, could be potentially used as coatings of a variety of implants for orthopedic applications.
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Adhesivos/química , Materiales Biomiméticos/química , Bivalvos/química , Materiales Biocompatibles Revestidos/química , Nácar/química , Adhesividad , Animales , Organismos Acuáticos , Bivalvos/fisiología , Quitosano/química , Vidrio/química , Ácido Hialurónico/química , Microscopía de Fuerza Atómica , Nanopartículas/química , Nanopartículas/ultraestructura , Proteínas/química , Proteínas/metabolismo , Tecnicas de Microbalanza del Cristal de CuarzoRESUMEN
Chitosan (CHI), a biocompatible and biodegradable polysaccharide with the ability to provide a non-protein matrix for tissue growth, is considered to be an ideal material in the biomedical field. However, the lack of good mechanical properties limits its applications. In order to overcome this drawback, CHI has been combined with different polymers and fillers, leading to a variety of chitosan-based nanocomposites. The extensive research on CHI nanocomposites as well as their main biomedical applications are reviewed in this paper. An overview of the different fillers and assembly techniques available to produce CHI nanocomposites is presented. Finally, the properties of such nanocomposites are discussed with particular focus on bone regeneration, drug delivery, wound healing and biosensing applications.
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We investigated the pH-dependent properties of multilayered films made of chitosan (CHI) and alginate (ALG) and focused on their postassembly response to different pH environments using a quartz crystal microbalance with dissipation monitoring (QCM-D), swelling studies, ζ potential measurements, and dynamic mechanical analysis (DMA). In an acidic environment, the multilayers presented lower dissipation values and, consequently, higher moduli when compared with the values obtained for the pH used during the assembly (5.5). When the multilayers were exposed to alkaline environments, the opposite behavior occurred. These results were further corroborated by the ability of this multilayered system to exhibit a reversible swelling-deswelling behavior within the pH range from 3 to 9. The changes in the physicochemical properties of the multilayer system were gradual and different from those of individual solubilized polyelectrolytes. This behavior is related to electrostatic interactions between the ionizable groups combined with hydrogen bonding and hydrophobic interactions. Beyond the pH range of 3-9, the multilayers were stabilized by genipin cross-linking. The multilayered films also became more rigid while the pH responsiveness conferred by the ionizable moieties of the polyelectrolytes was preserved. This work demonstrates the versatility and feasibility of LbL methodology to generate inherently pH stimulus-responsive nanostructured films. Surface functionalization using pH responsiveness endows several biomedical applications with abilities such as drug delivery, diagnostics, microfluidics, biosensing, and biomimetic implantable membranes.
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Alginatos/química , Quitosano/química , Electrólitos/química , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Enlace de Hidrógeno , Concentración de Iones de Hidrógeno , Tecnicas de Microbalanza del Cristal de Cuarzo , Electricidad EstáticaRESUMEN
In a marine environment, specific proteins are secreted by mussels and used as a bioglue to stick to a surface. These mussel proteins present an unusual amino acid 3,4-dihydroxyphenylalanine (known as DOPA). The outstanding adhesive properties of these materials in the sea harsh conditions have been attributed to the presence of the catechol groups present in DOPA. Inspired by the structure and composition of these adhesive proteins, dopamine-modified hyaluronic acid (HA-DN) prepared by carbodiimide chemistry is used to form thin and surface-adherent dopamine films. This conjugate was characterized by distinct techniques, such as nuclear magnetic resonance and ultraviolet spectrophotometry. Multilayer films are developed based on chitosan and HA-DN to form polymeric coatings using the layer-by-layer methodology. The nanostructured films formation is monitored by quartz crystal microbalance. The film surface is characterized by atomic force microscopy and scanning electron microscopy. Water contact angle measurements are also conducted. The adhesion properties are analyzed showing that the nanostructured films with dopamine promote an improved adhesion. In vitro tests show an enhanced cell adhesion, proliferation and viability for the biomimetic films with catechol groups, demonstrating their potential to be used in distinct biomedical applications.
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Quitosano/química , Materiales Biocompatibles Revestidos/síntesis química , Dopamina/química , Ácido Hialurónico/química , Membranas Artificiales , Nanoestructuras/química , Animales , Biomimética , Adhesión Celular/efectos de los fármacos , Células Cultivadas , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Humanos , Ensayo de Materiales , Ratones , Microscopía de Fuerza Atómica , Microscopía Electrónica de Rastreo , Polímeros/síntesis química , Polímeros/química , Polímeros/farmacología , Tecnicas de Microbalanza del Cristal de Cuarzo , Propiedades de Superficie , Andamios del Tejido/químicaRESUMEN
Targeted breast cancer therapies hold the potential to improve the efficiency of drug delivery to the pathology site without impacting the viability and function of healthy cells. Herein, we developed multifunctional nanocarriers that target simultaneously several downstream signaling processes in triple negative breast cancer cells. The system comprises pH sensitive CaCO3 nanoparticles (NPs) as carriers of the anticancer drug doxorubicin (DOX). The NPs were coated in a layer-by-layer (LbL) fashion using poly-l-lysine and hyaluronic acid to target receptors overexpressed in breast cancer (e.g. CD44, RHAMM). Spheroids of the triple-negative Hs578T cell line were used as a 3D model to assess the therapeutic potential of this system. Our results showed that the NPs act via a synergistic mechanism that combines Ca2+ overload causing cell calcification and DNA damage by DOX. The LbL coating was crucial for the protection of the healthy cells, i.e. it provides NPs with targeting capacity. The overall data suggests that the LbL-coated NPs loaded with DOX hold great potential for the treatment of breast cancer.
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Carbonato de Calcio , Doxorrubicina , Portadores de Fármacos , Nanopartículas , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Doxorrubicina/farmacología , Doxorrubicina/química , Doxorrubicina/administración & dosificación , Nanopartículas/química , Portadores de Fármacos/química , Carbonato de Calcio/química , Femenino , Supervivencia Celular/efectos de los fármacos , Línea Celular Tumoral , Calcio/metabolismo , Calcio/química , Tamaño de la Partícula , Polilisina/química , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/administración & dosificación , Propiedades de Superficie , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Ácido Hialurónico/químicaRESUMEN
The current treatments for wounds often fail to induce adequate healing, leaving wounds vulnerable to persistent infections and development of drug-resistant microbial biofilms. New natural-derived nanoparticles were studied to impair bacteria colonization and hinder the formation of biofilms in wounds. The nanoparticles were fabricated through polyelectrolyte complexation of chitosan (CS, polycation) and hyaluronic acid (HA, polyanion). UV-induced photo-crosslinking was used to enhance the stability of the nanoparticles. To achieve this, HA was methacrylated (HAMA, degree of modification of 20 %). Photo-crosslinked nanoparticles obtained from HAMA and CS had a diameter of 478 nm and a more homogeneous size distribution than nanoparticles assembled solely through complexation (742 nm). The nanoparticles were loaded with the antimicrobial agent bacitracin (BC), resulting in nanoparticles with a diameter of 332 nm. The encapsulation of BC was highly efficient (97 %). The BC-loaded nanoparticles showed significant antibacterial activity against gram-positive bacteria Staphylococcus aureus, Methicillin-resistant S. aureus and S. epidermidis. Photo-crosslinked HAMA/CS nanoparticles loaded with BC demonstrated inhibition of biofilm formation and a positive effect on the proliferation of mammalian cells (L929). These crosslinked nanoparticles have potential for the long-term treatment of wounds and controlled antibiotic delivery at the location of a lesion.
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Antibacterianos , Bacitracina , Biopelículas , Quitosano , Ácido Hialurónico , Nanopartículas , Quitosano/química , Quitosano/farmacología , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Nanopartículas/química , Antibacterianos/farmacología , Antibacterianos/química , Bacitracina/farmacología , Bacitracina/química , Biopelículas/efectos de los fármacos , Portadores de Fármacos/química , Metacrilatos/química , Metacrilatos/farmacología , Animales , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Reactivos de Enlaces Cruzados/química , RatonesRESUMEN
The central nervous system (CNS) has a limited ability to regenerate after a traumatic injury or a disease due to the low capacity of the neurons to re-grow and the inhibitory environment formed in situ. Current therapies include the use of drugs and rehabilitation, which do not fully restore the CNS functions and only delay the pathology progression. Tissue engineering offers a simple and versatile solution for this problem through the use of bioconstructs that promote nerve tissue repair by bridging cavity spaces. In this approach, the choice of biomaterial is crucial. Herein, we present recent advances in the design and development of adhesive and self-healing materials that support CNS healing. The adhesive materials have the advantage of promoting recovery without the use of needles or sewing, while the self-healing materials have the capacity to restore the tissue integrity without the need for external intervention. These materials can be used alone or in combination with cells and/or bioactive agents to control the inflammation, formation of free radicals, and proteases activity. We discuss the advantages and drawbacks of different systems. The remaining challenges that can bring these materials to clinical reality are also briefly presented.
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Adhesivos , Materiales Biocompatibles , Adhesivos/uso terapéutico , Materiales Biocompatibles/uso terapéutico , Sistema Nervioso Central/lesiones , Ingeniería de Tejidos , NeuronasRESUMEN
Breast cancer is resistant to conventional treatments due to the specific tumour microenvironment, the associated acidic pH and the overexpression of receptors that enhance cells tumorigenicity. Herein, we optimized the synthesis of acidic resorbable calcium carbonate (CaCO3) nanoparticles and the encapsulation of a low molecular weight model molecule (Rhodamine). The addition of ethylene glycol during the synthetic process resulted in a particle size decrease: we obtained homogeneous CaCO3 particles with an average size of 564 nm. Their negative charge enabled the assembly of layer-by-layer (LbL) coatings with surface-exposed hyaluronic acid (HA), a ligand of tumour-associated receptor CD44. The coating decreased Rhodamine release by two-fold compared to uncoated nanoparticles. We demonstrated the effect of nanoparticles on two breast cancer cell lines with different aggressiveness - SK-BR-3 and the more aggressive MDA-MB-231 - and compared them with the normal breast cell line MCF10A. CaCO3 nanoparticles (coated and uncoated) significantly decreased the metabolic activity of the breast cancer cells. The interactions between LbL-coated nanoparticles and cells depended on HA expression on the cell surface: more particles were observed on the surface of MDA-MB-231 cells, which had the thickest endogenous HA coating. We concluded that CaCO3 nanoparticles are potential candidates to carry low molecular weight chemotherapeutics and deliver them to aggressive breast cancer sites with an HA-abundant pericellular matrix.
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Neoplasias de la Mama , Nanopartículas , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Carbonato de Calcio/farmacología , Carbonato de Calcio/química , Células MCF-7 , Rodaminas , Nanopartículas/química , Microambiente TumoralRESUMEN
Three-dimensional (3D) printing technology has become a popular tool to produce complex structures. It has great potential in the regenerative medicine field to produce customizable and reproducible scaffolds with high control of dimensions and porosity. This study was focused on the investigation of new biocompatible and biodegradable 3D-printed scaffolds with suitable mechanical properties to assist tendon and ligament regeneration. Polylactic acid (PLA) scaffolds were reinforced with 0.5 wt.% of functionalized graphite nanoplatelets decorated with silver nanoparticles ((f-EG)+Ag). The functionalization of graphene was carried out to strengthen the interface with the polymer. (f-EG)+Ag exhibited antibacterial properties against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), an important feature for the healing process and prevention of bacterial infections. The scaffolds' structure, biodegradation, and mechanical properties were assessed to confirm their suitability for tendon and ligamentregeneration. All scaffolds exhibited surface nanoroughness created during printing, which was increased by the filler presence. The wet state dynamic mechanical analysis proved that the incorporation of reinforcement led to an increase in the storage modulus, compared with neat PLA. The cytotoxicity assays using L929 fibroblasts showed that the scaffolds were biocompatible. The PLA+[(f-EG)+Ag] scaffolds were also loaded with human tendon-derived cells and showed their capability to maintain the tenogenic commitment with an increase in the gene expression of specific tendon/ligament-related markers. The results demonstrate the potential application of these new 3D-printed nanocomposite scaffolds for tendon and ligament regeneration.
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OBJECTIVE: To investigate the effects of different physical exercise programs and polymorphisms of the FTO (fat mass and obesity-associated gene) on body composition and cardiovascular risk factors in adolescents with overweight and obesity. METHODS: A randomized, parallel, double-blind clinical trial consisting of the adolescent overweight from the state public network, in a simple representative random sample, who participated in an aerobic exercise or weight training intervention for 10 weeks. Anthropometry, body composition, biochemical markers, sexual maturation, and rs9939609 polymorphism in the FTO gene were assessed. 347 adolescents had their characterization of nutritional status. 72 individuals with overweight and obesity were invited to participate. 39 remained for the start of the program and were randomly allocated to both types of intervention. In the end, 26 subjects participated in the intervention programs, with 12 and 14 in the aerobic and weight training programs, respectively. RESULTS: Heterozygous and homozygous bearers of risk allele A participating in the aerobic program showed improvements in glycemia (p = 0.002) and total cholesterol (p = 0.023) and a reduction in body fat mass (p = 0.041). The weight training program reduced glycemia in patients with the risk allele A (p = 0.027). Cameron's stage four sexual maturation participants were 2.1 times more likely to improve their body fat (CI = 1.31-3.39). CONCLUSION: Aerobic exercises produced exclusively a significant decrease in fat mass and total cholesterol in patients with risk allele A. Distinct physical exercise programs may cause diverse changes in risk variables related to the health of adolescents.
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Enfermedades Cardiovasculares , Obesidad Infantil , Humanos , Adolescente , Sobrepeso , Índice de Masa Corporal , Factores de Riesgo , Ejercicio Físico , Tejido Adiposo , Factores de Riesgo de Enfermedad Cardiaca , Colesterol , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Mussels secrete protein-based byssal threads to tether to rocks, ships, and other organisms underwater. The secreted marine mussel adhesive proteins (MAPs) contain the peculiar amino acid L-3,4-dihydroxyphenylalanine (DOPA), whose catechol group content contributes greatly to their outstanding adhesive properties. Inspired by such mussel bioadhesion, we demonstrate that catechol-modified polysaccharides can be used to obtain adhesive membranes using the compaction of polyelectrolyte complexes (CoPEC) method. It is a simple and versatile approach that uses polyelectrolyte complexes as building blocks that coalesce and dry as membrane constructs simply as a result of sedimentation and mild temperature. We used two natural and biocompatible polymers: chitosan (CHI) as a polycation and hyaluronic acid (HA) as a polyanion. The CoPEC technique also allowed the entrapment of ternary bioactive glass nanoparticles to stimulate mineralization. Moreover, combinations of these polymers modified with catechol groups were made to enhance the adhesive properties of the assembled membranes. Extensive physico-chemical characterization was performed to investigate the successful production of composite CoPEC membranes in terms of surface morphology, wettability, stability, mechanical performance, in vitro bioactivity, and cellular behavior. Considering the promising properties exhibited by the obtained membranes, new adhesives suitable for the regeneration of hard tissues can be envisaged.
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We describe bioadhesive membranes developed from marine renewable biomaterials, namely chitosan and collagen extracted from fish skins. Collagen was functionalized with catechol groups (Coll-Cat) to provide the membranes with superior adhesive properties in a wet environment and blended with chitosan to improve the mechanical properties. The blended membranes were compared to chitosan and chitosan blended with unmodified collagen in terms of surface morphology, wettability, weight loss, water uptake, mechanical and adhesive properties. The metabolic activity, the viability and the morphology of L929 fibroblastic cells seeded on these membranes were also assessed. Our results show that the functionalization with catechol groups improves the adhesive and mechanical properties of the membranes and enhances cell attachment and proliferation. These data suggest that the developed marine origin-raw membranes present a potential towards the restoration of the structural and functional properties of damaged soft tissues.
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Quitosano , Adhesivos/química , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Catecoles/química , Quitosano/química , Colágeno/química , Membranas ArtificialesRESUMEN
In this paper, we describe the construction and characteristics of thermoresponsive, thin nanostructured films prepared by layer-by-layer sequential assembly of chitosan-graft-NIPAAm and alginate. FTIR and (1)H NMR spectra have confirmed the introduction of NIPAAm moieties onto the chitosan backbone. The LCST of the synthesized copolymer was found to be around 31-33 °C. The formation of the polyelectrolyte multilayers containing the copolymer and alginate was followed in situ by quartz crystal microbalance with dissipation monitoring technique and ex situ by UV-vis measurements. Our results revealed the linear increase of the multilayer film growth and the influence of the presence of salt. Moreover, AFM analysis has confirmed that PNIPAAm is able to reconform upon temperature swaps even when combined with other layers in a polyelectrolyte multilayer, demonstrating that the nanoassemblies are thermoresponsive. Preliminary results showed that, upon reducing culture temperature below PNIPAAm LCST, a gradual detachment of cell sheets from these PNIPAAm-based coatings has occurred.
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Investigación Biomédica , Membranas Artificiales , Nanoestructuras/química , Acrilamidas/química , Resinas Acrílicas , Quitosano/química , Tamaño de la Partícula , Polímeros/química , Tecnicas de Microbalanza del Cristal de Cuarzo , Propiedades de SuperficieRESUMEN
Spin-coating is a widely employed technique for the fabrication of thin-film coatings over large areas with smooth and homogeneous surfaces. In recent years, research has extended the scope of spin-coating by developing methods involving the interface of the substrate and the deposited solution to obtain self-supported films, also called freestanding films. Thereby, such structures have been developed for a wide range of areas. Biomedical applications of spin-coated freestanding films include wound dressings, drug delivery, and biosensing. This review will discuss the fundamental physical and chemical processes governing the conventional spin-coating as well as the techniques to obtain freestanding films. Furthermore, developments within this field with a primary focus on tissue engineering applications will be reviewed.
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Materiales Biocompatibles Revestidos/química , Animales , Vendajes , Portadores de Fármacos/química , Membranas Artificiales , Nanoestructuras/química , Polímeros/química , Ingeniería de TejidosRESUMEN
The anterior cruciate ligament (ACL) is one of the most prone to injury in the human body. Due to its insufficient vascularization and low regenerative capacity, surgery is often required when it is ruptured. Most of the current tissue engineering (TE) strategies are based on scaffolds produced with fibers due to the natural ligament's fibrous structure. In the present work, composite filaments based on poly(L-lactic acid) (PLA) reinforced with graphite nanoplatelets (PLA+EG) as received, chemically functionalized (PLA+f-EG), or functionalized and decorated with silver nanoparticles [PLA+((f-EG)+Ag)] were produced by melt mixing, ensuring good filler dispersion. These filaments were produced with diameters of 0.25 mm and 1.75 mm for textile-engineered and 3D-printed ligament scaffolds, respectively. The resulting composite filaments are thermally stable, and the incorporation of graphite increases the stiffness of the composites and decreases the electrical resistivity, as compared to PLA. None of the filaments suffered significant degradation after 27 days. The composite filaments were processed into 3D scaffolds with finely controlled dimensions and porosity by textile-engineered and additive fabrication techniques, demonstrating their potential for ligament TE applications.
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In this study, composite scaffolds based on poly(caprolactone) (PCL) and non-covalently functionalized few-layer graphene (FLG) were manufactured by an extrusion-based system for the first time. For that, functionalized FLG powder was obtained through the evaporation of a functionalized FLG aqueous suspension prepared from a graphite precursor. Cryomilling was shown to be an efficient mixing method, producing a homogeneous dispersion of FLG particles onto the PCL polymeric matrix. Thereafter, fused deposition modeling (FDM) was used to print 3D scaffolds and their morphology, thermal, biodegradability, mechanical, and cytotoxicity properties were analysed. The presence of functionalized FLG demonstrated to induce slight changes in the microstructure of the scaffold, did not affect the thermal stability and enhanced significantly the compressive modulus. The composite scaffolds presented a porosity of around 40% and a mean pore size in the range of 300 µm. The cell viability and proliferation of SaOs-2 cells were assessed and the results showed good cell viability and long-term proliferation onto produced composite scaffolds. Therefore, these new FLG/PCL scaffolds comprised adequate morphological, thermal, mechanical, and biological properties to be used in bone tissue regeneration.