RESUMEN

Hydrogels based on natural polymers have aroused interest from the scientific community. The aim of this investigation was to obtain natural extracts from mango peels and to evaluate their addition (1, 3, and 5%) on the rheological behavior of mango starch hydrogels. The total phenolic content, antioxidant activities, and phenolic acid profile of the natural extracts were evaluated. The viscoelastic and thixotropic behavior of hydrogels with the addition of natural extracts was evaluated. The total phenol content and antioxidant activity of the extracts increased significantly (p<0.05) with the variation of the ethanol-water ratio; the phenolic acid profile showed the contain of p-coumaric, ellagic, ferulic, chlorogenic acids, epicatechein, catechin, querecetin, and mangiferin. The viscoelastic behavior of the hydrogels showed that the storage modulus G' is larger than the loss modulus G'' indicating a viscoelastic solid behavior. The addition of extract improved the thermal stability of the hydrogels. 1% of the extracts increase viscoelastic and thixotropic properties, while concentrations of 3 to 5% decreased. The recovery percentage (%Re) decreases at concentrations from 0% to 1% of natural extracts, however, at concentrations from 3% to 5% increased.

Asunto(s)

Antioxidantes , Hidrogeles , Mangifera , Extractos Vegetales , Reología , Almidón , Mangifera/química , Hidrogeles/química , Extractos Vegetales/química , Almidón/química , Antioxidantes/química , Viscosidad , Frutas/química , Fenoles/química

RESUMEN

Herein, four different grafted chitosans were synthesized by covalent attachment of glycine, L-arginine, L-glutamic acid, or L-cysteine to the chitosan chains. All products were subsequently permethylated to obtain their corresponding quaternary ammonium salts to enhance the inherent antimicrobial properties of native chitosan. In all cases, transparent hydrogels with the following remarkable characteristics were obtained: i) high-water absorption capacity (32-44 g H2O per g of polymer), ii) viscoelastic behavior at low deformations, iii) flexibility when subjected to deformations and iv) stability over long time scales. All the permethylated derivatives successfully inhibited 100 % of the growth of S. aureus. They also exhibited higher antimicrobial activity against E. coli than native chitosan. The structure of the chemically crosslinked products was more stable under external perturbations than that of the physically crosslinked ones. Between the chemically crosslinked products, the permethylated glutamic acid-grafted chitosan exhibited a noteworthy higher water absorption capacity with respect to that modified with cysteine, which makes it the most promising material for various industrial applications, including biomedical and food industries. Regarding biomedical applications, this derivative met the required physicochemical criteria for wound dressings, which encourages the pursuit of biological studies necessary to ensure the safety of its use for this application.

Asunto(s)

Vendajes , Quitosano , Hidrogeles , Quitosano/química , Quitosano/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Hidrogeles/síntesis química , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Agua/química , Cicatrización de Heridas/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología

RESUMEN

Large bone defects are a significant health problem today with various origins, including extensive trauma, tumours, or congenital musculoskeletal disorders. Tissue engineering, and in particular bone tissue engineering, aims to respond to this demand. As such, we propose a specific model based on Elastin-Like Recombinamers-based click-chemistry hydrogels given their high biocompatibility and their potent on bone regeneration effect conferred by different bioactive sequences. In this work we demonstrate, using biochemistry, histology, histomorphometry and imaging techniques, the biocompatibility of our matrix and its potent effect on bone regeneration in a model of bone parietal lesion in female New Zealand rabbits.

Asunto(s)

Materiales Biocompatibles , Regeneración Ósea , Elastina , Hidrogeles , Ingeniería de Tejidos , Animales , Femenino , Conejos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Regeneración Ósea/efectos de los fármacos , Química Clic/métodos , Elastina/química , Hidrogeles/química , Hidrogeles/farmacología , Ingeniería de Tejidos/métodos , Andamios del Tejido/química

RESUMEN

Osteomyelitis is an inflammation of bone tissue usually caused by pyogenic bacteria. The most recurrent clinical approach consists of bone debridement followed by parenteral administration of antibiotics. However, systemic antibiotic treatment has limitations regarding absorption rate and bioavailability over time. The main challenge of osteomyelitis treatment consists of coupling the persistent infection treatment with the regeneration of the bone debrided. In this work, we developed an injectable drug delivery system based on poloxamer 407 hydrogel containing undoped Mg, Zn-doped tricalcium phosphate (ß-TCP), and teicoplanin, a broad-spectrum antibiotic. We evaluated how the addition of teicoplanin and ß-TCP affected the micellization, gelation, particle size, and surface charge of the hydrogel. Later, we studied the hydrogel degradation and drug delivery kinetics. Finally, the bactericidal, biocompatibility, and osteogenic properties were evaluated through in vitro studies and confirmed by in vivo Wistar rat models. Teicoplanin was found to be encapsulated in the corona portions of the hydrogel micelles, yielding a bigger hydrodynamics radius. The encapsulated teicoplanin showed a sustained release over the evaluated period, enough to trigger antibacterial properties against Gram-positive bacteria. Besides, the formulations were biocompatible and showed bone healing ability and osteogenic properties. Finally, in vivo studies confirmed that the proposed locally injected formulations yielded osteomyelitis treatment with superior outcomes than parenteral administration while promoting bone regeneration. In conclusion, the presented formulations are promising drug delivery systems for osteomyelitis treatment and deserve further technological improvements.

Asunto(s)

Antibacterianos , Fosfatos de Calcio , Hidrogeles , Osteogénesis , Osteomielitis , Ratas Wistar , Teicoplanina , Osteomielitis/tratamiento farmacológico , Osteomielitis/microbiología , Animales , Fosfatos de Calcio/química , Teicoplanina/administración & dosificación , Teicoplanina/farmacología , Teicoplanina/química , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Antibacterianos/química , Ratas , Hidrogeles/química , Hidrogeles/administración & dosificación , Osteogénesis/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Humanos , Staphylococcus aureus/efectos de los fármacos , Poloxámero/química

RESUMEN

Actinic cheilitis (AC) is a lip disorder, with no standard treatment. Imiquimod (IMIQ) is an immunomodulator that treat precancerous lesions; however, its commercial form causes severe adverse effects. This study aimed to assess IMQ release from a chitosan hydrogel containing 0.05 % nanoencapsulated (NANO) imiquimod (IMIQ-0.05 %-NANO) and its efficacy in AC treatment. The hydrogels were prepared by incorporating chitosan into polymeric nanocapsules (NCimiq) loaded with IMQ, produced using the interfacial deposition of preformed polymer method. IMQ release was evaluated using automated Franz Cells. A triple-blind randomized controlled trial (49 subjects) compared the efficacy of: IMIQ-0.05 %-NANO, 5 % free imiquimod (IMIQ-5 %), 0.05 % free imiquimod (IMIQ-0.05 %), and placebo hydrogel. The IMIQ-NANO-0.05 % and IMIQ-5 % groups exhibited significantly higher rates of clinical improvement (p < 0.05); however, the IMIQ-5 % group experienced more adverse effects (92.3 % of subjects) compared to other groups (p < 0.05). In conclusion, in the studied sample, IMIQ-NANO-0.05 % was a safe and effective option to treat AC.

Asunto(s)

Queilitis , Hidrogeles , Imiquimod , Humanos , Imiquimod/administración & dosificación , Queilitis/tratamiento farmacológico , Queilitis/patología , Masculino , Femenino , Persona de Mediana Edad , Hidrogeles/química , Nanocápsulas/química , Quitosano/química , Liberación de Fármacos , Adulto , Resultado del Tratamiento , Anciano

RESUMEN

Producing food in quantity and quality to meet the growing population demand is a challenge for the coming years. In addition to the need to improve the use and efficiency of conventional agricultural inputs, we face climate change and disparity in access to food. In this context, creating innovative, efficient, and ecologically approaches is necessary to transform this global scenario. Several delivery systems are being developed to encapsulate agrochemicals, aiming to improve the controlled release of active ingredients and protect them against environmental biotic and abiotic factors. Among these systems, hydrogel spheres are particularly notable for their ability to be fabricated from biodegradable materials, allowing the encapsulation of molecules, nanomaterials, and even organisms (e.g., bacteria and fungi). This review provides an overview of the latest progress in developing polysaccharide-based hydrogel spheres for agriculture. In addition, we describe methods for preparing hydrogel spheres and discuss the encapsulation and release of agricultural inputs in the field. Finally, we put hydrogel spheres into perspective and seek to highlight some current challenges in the field to spark new inspiration and improve the development of environmentally friendly and cost-effective delivery systems for the agricultural sector.

Asunto(s)

Agricultura , Preparaciones de Acción Retardada , Hidrogeles , Polisacáridos , Hidrogeles/química , Agricultura/métodos , Polisacáridos/química , Agroquímicos/química

RESUMEN

Envisaging to improve the evaluation of ophthalmic drug products while minimizing the need for animal testing, our group developed the OphthalMimic device, a 3D-printed device that incorporates an artificial lacrimal flow, a cul-de-sac area, a moving eyelid, and a surface that interacts effectively with ophthalmic formulations, thereby providing a close representation of human ocular conditions. An important application of such a device would be its use as a platform for dissolution/release tests that closely mimic in vivo conditions. However, the surface that artificially simulates the cornea should have a higher resistance (10 min) than the previously described polymeric films (5 min). For this key assay upgrade, we describe the process of obtaining and thoroughly characterizing a hydrogel-based hybrid membrane to be used as a platform base to simulate the cornea artificially. Also, the OphthalMimic device suffered design improvements to fit the new membrane and incorporate the moving eyelid. The results confirmed the successful synthesis of the hydrogel components. The membrane's water content (86.25 ± 0.35 %) closely mirrored the human cornea (72 to 85 %). Furthermore, morphological analysis supported the membrane's comparability to the natural cornea. Finally, the performance of different formulations was analysed, demonstrating that the device could differentiate their drainage profile through the viscosity of PLX 14 (79 ± 5 %), PLX 16 (72 ± 4 %), and PLX 20 (57 ± 14 %), and mucoadhesion of PLXCS0.5 (69 ± 1 %), PLX16CS1.0 (65 ± 3 %), PLX16CS1.25 (67 ± 3 %), and the solution (97 ± 8 %). In conclusion, using the hydrogel-based hybrid membrane in the OphthalMimic device represents a significant advancement in the field of ophthalmic drug evaluation, providing a valuable platform for dissolution/release tests. Such a platform aligns with the ethical mandate to reduce animal testing and promises to accelerate the development of safer and more effective ophthalmic drugs.

Asunto(s)

Hidrogeles , Humanos , Hidrogeles/química , Soluciones Oftálmicas/química , Impresión Tridimensional , Córnea/efectos de los fármacos , Córnea/metabolismo , Administración Oftálmica , Membranas Artificiales

RESUMEN

The objective of this study was to create injectable photo-crosslinkable biomaterials, using gelatin methacryloyl (GelMA) hydrogel, combined with a decellularized bone matrix (BMdc) and a deproteinized (BMdp) bovine bone matrix. These were intended to serve as bioactive scaffolds for dentin regeneration. The parameters for GelMA hydrogel fabrication were initially selected, followed by the incorporation of BMdc and BMdp at a 1% (w/v) ratio. Nano-hydroxyapatite (nHA) was also included as a control. A physicochemical characterization was conducted, with FTIR analysis indicating that the mineral phase was complexed with GelMA, and BMdc was chemically bonded to the amide groups of gelatin. The porous structure was preserved post-BMdc incorporation, with bone particles incorporated alongside the pores. Conversely, the mineral phase was situated inside the pore opening, affecting the degree of porosity. The mineral phase did not modify the degradability of GelMA, even under conditions of type I collagenase-mediated enzymatic challenge, allowing hydrogel injection and increased mechanical strength. Subsequently, human dental pulp cells (HDPCs) were seeded onto the hydrogels. The cells remained viable and proliferative, irrespective of the GelMA composition. All mineral phases resulted in a significant increase in alkaline phosphatase activity and mineralized matrix deposition. However, GelMA-BMdc exhibited higher cell expression values, significantly surpassing those of all other formulations. In conclusion, our results showed that GelMA-BMdc produced a porous and stable hydrogel, capable of enhancing odontoblastic differentiation and mineral deposition when in contact with HDPCs, thereby showing potential for dentin regeneration.

Asunto(s)

Pulpa Dental , Dentina , Gelatina , Ingeniería de Tejidos , Dentina/química , Ingeniería de Tejidos/métodos , Animales , Bovinos , Gelatina/química , Humanos , Pulpa Dental/citología , Metacrilatos/química , Reactivos de Enlaces Cruzados/química , Hidrogeles/química , Andamios del Tejido/química , Huesos , Células Cultivadas , Porosidad

RESUMEN

In this study, a series of hydrogels were synthesized from chitosan(s) that was crosslinking with glutaraldehyde at different concentrations. Ascorbic acid in an acidic medium was used to facilitate non-covalent interactions. The chitosan(s) was obtained from shrimp cytoskeleton; while ascorbic acid was extracted from xoconostle juice. The hydrogel reaction was monitored by UV-vis spectroscopy (550 nm) to determine the reaction kinetics and reaction order at 60 °C. The hydrogels structures were characterized by NMR, FT-IR, HR-MS and SEM, while the degree of cross-linking was examined with TGA-DA. The extracellular matrices were obtained as stable hydrogels where reached maximum crosslinking was of 7 %, independent of glutaraldehyde quantity added. The rheological properties showed a behavior of weak gels and a dependence of crosslinking agent concentration on strength at different temperatures. The cytotoxicity assay showed that the gels had no adverse effects on cellular growth for all concentrations of glutaraldehyde.

Asunto(s)

Materiales Biocompatibles , Quitosano , Hidrogeles , Ingeniería de Tejidos , Hidrogeles/química , Hidrogeles/síntesis química , Materiales Biocompatibles/química , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/farmacología , Quitosano/química , Quitosano/farmacología , Quitosano/síntesis química , Animales , Glutaral/química , Reología , Reactivos de Enlaces Cruzados/química

RESUMEN

PURPOSE: To evaluate using a biocellulose-based hydrogel as an adjuvant in the healing process of arterial ulcers. METHODS: A prospective single group quasi-experimental study was carried out with chronic lower limb arterial ulcer patients. These patients received biocellulose-based hydrogel dressings and outpatient guidance on dressing and periodic reassessments. The primary outcomes were the ulcer-healing rate and product safety, which were assessed by ulcer area measured in photographic records of pre-treatment and posttreatment after 7, 30, and 60 days. Secondary outcomes were related to clinical assessment by the quality-of-life scores (SF-36 and EQ-5D) and pain, evaluated by the visual analogue scale (VAS). RESULTS: Seventeen participants were included, and one of them was excluded. Six patients (37%) had complete wound healing, and all patients had a significant reduction in the ulcer area during follow-up (233.6mm2 versus 2.7mm2) and reduction on the score PUSH 3.0 (p < 0.0001). The analysis of the SF-36 and EQ-5D questionnaires showed a statistically significant improvement in almost all parameters analyzed and with a reduction of pain assessed by the VAS. CONCLUSIONS: The biocellulose-based hydrogel was safe and showed a good perspective to promoting the necessary conditions to facilitate partial or complete healing of chronic arterial ulcers within a 60-day follow-up. Quality of life and pain were positively affected by the treatment.

Asunto(s)

Calidad de Vida , Cicatrización de Heridas , Humanos , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Resultado del Tratamiento , Enfermedad Crónica , Celulosa/uso terapéutico , Celulosa/administración & dosificación , Úlcera de la Pierna/terapia , Vendajes , Anciano de 80 o más Años , Dimensión del Dolor , Hidrogeles/uso terapéutico

RESUMEN

PURPOSE: Bacterial cellulose (BC) has shown high capacity for the treatment of wounds and burns, providing a moisty environment. Calcium alginate can be associated with BC to create gels that aid in wound debridement and contribute to appropriate wound healing. This study is aimed at characterizing and evaluating the use of bacterial cellulose/alginate gel in skin burns in rats. METHODS: Cellulose and cellulose/alginate gels were compared regarding the capacity of liquid absorption, moisture, viscosity, and potential cytotoxicity. The 2nd degree burns were produced using an aluminum metal plate (2.0cm) at 120ºC for 20s on the back of rats. The animals were divided into non-treated, CMC(Carboxymethylcellulose), Cellulose(CMC with bacterial cellulose), and Cellulose/alginate(CMC with bacterial cellulose and alginate). The animals received topical treatment 3 times/week. Biochemical (MPO, NAG and oxidative stress), histomorphometry and immunohistochemical assays (IL-1ß IL-10 and VEGF) were conducted on the 14th, 21st, 28th, and 35th days. RESULTS: Cellulose/Alginate gel showed higher absorption capacity and viscosity compared to Cellulose gel, with no cytotoxic effects. Cellulose/alginate presented lower MPO values, a higher percentage of IL-10, with greater and balanced oxidative stress profile. CONCLUSIONS: The use of cellulose/alginate gel reduced neutrophils and macrophage activation and showed greater anti-inflammatory response, which can contribute to healing chronic wounds and burns.

Asunto(s)

Alginatos , Quemaduras , Celulosa , Hidrogeles , Ratas Wistar , Cicatrización de Heridas , Animales , Alginatos/uso terapéutico , Celulosa/uso terapéutico , Quemaduras/tratamiento farmacológico , Quemaduras/terapia , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/uso terapéutico , Masculino , Ratas , Ácido Glucurónico/uso terapéutico , Ácidos Hexurónicos/uso terapéutico , Reproducibilidad de los Resultados , Viscosidad , Estrés Oxidativo/efectos de los fármacos , Inmunohistoquímica , Factores de Tiempo , Piel/lesiones , Piel/efectos de los fármacos

RESUMEN

Scaffolds for the filling and regeneration of osteochondral defects are a current challenge in the biomaterials field, and solutions with greater functionality are still being sought. The novel approach of this work was to obtain scaffolds with biologically active additives possessing microstructural, permeability, and mechanical properties, mimicking the complexity of natural cartilage. Four types of scaffolds with a gelatin/alginate matrix modified with hydroxyapatite were obtained, and the relationship between the modifiers and substrate properties was evaluated. They differed in the type of second modifier used, which was hydrated MgCl2 in two proportions, ZnO, and nanohydroxyapatite. The samples were obtained by freeze-drying by using two-stage freezing. Based on microstructural observations combined with X-ray microanalysis, the microstructure of the samples and the elemental content were assessed. Permeability and mechanical tests were also performed. The scaffolds exhibited a network of interconnected pores and complex microarchitecture, with lower porosity at the surface (15 ± 7 to 29 ± 6%) and higher porosity at the center (67 ± 8 to 75 ± 8%). The additives had varying effects on the pore sizes and permeabilities of the samples. ZnO yielded the most permeable scaffolds (5.92 × 10-11 m2), whereas nanohydroxyapatite yielded the scaffold with the lowest permeability (1.18 × 10-11 m2), values within the range reported for trabecular bone. The magnesium content had no statistically significant effect on the permeability. The best mechanical parameters were obtained for ZnO samples and those containing hydrated MgCl2. The scaffold's properties meet the criteria for filling osteochondral defects. The developed scaffolds follow a biomimetic approach in terms of hierarchical microarchitecture and mechanical parameters as well as chemical composition. The obtained composite materials have the potential as biomimetic scaffolds for the regeneration of osteochondral defects.

Asunto(s)

Hidrogeles , Cloruro de Magnesio , Andamios del Tejido , Óxido de Zinc , Óxido de Zinc/química , Andamios del Tejido/química , Cloruro de Magnesio/química , Hidrogeles/química , Porosidad , Alginatos/química , Durapatita/química , Permeabilidad , Gelatina/química , Ensayo de Materiales

RESUMEN

The significance of accurate determination of ethanol content in hydrogel formulations was accentuated during COVID-19 pandemic coinciding with the heightened demand for sanitizing agents. The present article proposes three robust methodologies for this purpose: Fourier Transform Infrared Spectroscopy (FTIR), Raman spectroscopy, and Densitometry with matrix effect correction by Near-Infrared Spectroscopy (NIR). All three methods demonstrated outstanding linearity (R2 ≥ 0.99) and minimal errors (< 1.7%), offering simplicity and operational efficiency. FTIR and Raman, being non-destructive and requiring minimal preparation, enable practical on-site analysis capabilities, underscoring the potential of the spectroscopic methods to expedite health investigations and inspections, empowering on-site ethanol determination, and relieving the burden on official laboratories. Additionally, the densitometry with NIR-based approach showcased superior accuracy and precision compared to spectroscopic methods, meeting validation criteria while offering operational advantages over the costly official distillation-based method. Therefore, it stands as a reliable and reproducible technique for comprehensive health and criminal compliance assessments, making it a compelling alternative for both industry and official laboratories.

Asunto(s)

Etanol , Hidrogeles , Espectrometría Raman , Hidrogeles/química , Etanol/química , Etanol/análisis , Espectrometría Raman/métodos , Humanos , Espectroscopía Infrarroja por Transformada de Fourier , COVID-19 , Espectroscopía Infrarroja Corta/métodos

RESUMEN

A key strategy in enhancing the efficacy of collagen-based hydrogels involves incorporating polysaccharides, which have shown great promise for wound healing. In this study, semi-interpenetrating polymeric network (semi-IPN) hydrogels comprised of collagen (Col) with the macrocyclic oligosaccharide ß-cyclodextrin (ß-CD) (20-80 wt.%) were synthesised. Fourier-transform infrared (FTIR) spectroscopy confirmed the successful fabrication of these Col/ß-CD hydrogels, evidenced by the presence of characteristic absorption bands, including the urea bond band at ∼1740 cm-1, related with collagen crosslinking. Higher ß-CD content was associated with increased crosslinking, higher swelling, and faster gelation. The ß-CD content directly influenced the morphology and semi-crystallinity. All Col/ß-CD hydrogels displayed superabsorbent properties, enhanced thermal stability, and exhibited slow degradation rates. Mechanical properties were significantly improved with contents higher than ß-CD 40 wt.%. These hydrogels inhibited the growth of Escherichia coli bacteria and facilitated the controlled release of agents, such as malachite green, methylene blue, and ketorolac. The chemical composition of the Col/ß-CD hydrogels did not induce cytotoxic effects on monocytes and fibroblast cells. Instead, they actively promoted cellular metabolic activity, encouraging cell growth and proliferation. Moreover, cell signalling modulation was observed, leading to changes in the expression of TNF-α and IL-10 cytokines. In summary, the results of this research indicate that these novel hydrogels possess multifunctional characteristics, including biocompatibility, super-swelling capacity, good thermal, hydrolytic, and enzymatic degradation resistance, antibacterial activity, inflammation modulation, and the ability to be used for controlled delivery of therapeutic agents, indicating high potential for application in advanced wound dressings.

Asunto(s)

Antibacterianos , Vendajes , Colágeno , Preparaciones de Acción Retardada , Liberación de Fármacos , Escherichia coli , Hidrogeles , beta-Ciclodextrinas , Hidrogeles/química , Hidrogeles/farmacología , beta-Ciclodextrinas/química , Antibacterianos/farmacología , Antibacterianos/química , Preparaciones de Acción Retardada/química , Colágeno/química , Escherichia coli/efectos de los fármacos , Humanos , Cicatrización de Heridas/efectos de los fármacos , Inflamación/tratamiento farmacológico , Animales , Ratones

RESUMEN

Tumor-on-chips (ToCs) are useful platforms for studying the physiology of tumors and evaluating the efficacy and toxicity of anti-cancer drugs. However, the design and fabrication of a ToC system is not a trivial venture. We introduce a user-friendly, flexible, 3D-printed microfluidic device that can be used to culture cancer cells or cancer-derived spheroids embedded in hydrogels under well-controlled environments. The system consists of two lateral flow compartments (left and right sides), each with two inlets and two outlets to deliver cell culture media as continuous liquid streams. The central compartment was designed to host a hydrogel in which cells and microtissues can be confined and cultured. We performed tracer experiments with colored inks and 40 kDa fluorescein isothiocyanate dextran to characterize the transport/mixing performances of the system. We also cultured homotypic (MCF7) and heterotypic (MCF7-BJ) spheroids embedded in gelatin methacryloyl hydrogels to illustrate the use of this microfluidic device in sustaining long-term micro-tissue culture experiments. We further demonstrated the use of this platform in anticancer drug testing by continuous perfusion of doxorubicin, a commonly used anti-cancer drug for breast cancer. In these experiments, we evaluated drug transport, viability, glucose consumption, cell death (apoptosis), and cytotoxicity. In summary, we introduce a robust and friendly ToC system capable of recapitulating relevant aspects of the tumor microenvironment for the study of cancer physiology, anti-cancer drug transport, efficacy, and safety. We anticipate that this flexible 3D-printed microfluidic device may facilitate cancer research and the development and screening of strategies for personalized medicine.

Asunto(s)

Antineoplásicos , Neoplasias de la Mama , Impresión Tridimensional , Esferoides Celulares , Humanos , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/patología , Esferoides Celulares/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Femenino , Células MCF-7 , Hidrogeles/química , Dispositivos Laboratorio en un Chip , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Dextranos/química , Gelatina/química , Doxorrubicina/farmacología , Doxorrubicina/química , Supervivencia Celular/efectos de los fármacos , Metacrilatos

RESUMEN

This study explored the photocatalytic hydrogen evolution reaction (HER) using novel biohydrogel composites comprising chitosan, and a photocatalyst consisting in TiO2 P25 decorated with Au and/or Cu mono- and bimetallic nanoparticles (NPs) to boost its optical and catalytic properties. Low loads of Cu and Au (1 mol%) were incorporated onto TiO2 via a green photodeposition methodology. Characterization techniques confirmed the incorporation of decoration metals as well as improvements in the light absorption properties in the visible light interval (λ > 390 nm) and electron transfer capability of the semiconductors. Thereafter, Au and/or Cu NP-supported TiO2 were incorporated into chitosan-based physically crosslinked hydrogels revealing significant interactions between chitosan functional groups (hydroxyls, amines and amides) with the NPs to ensure its encapsulation. These materials were evaluated as photocatalysts for the HER using water and methanol mixtures under simulated sunlight and visible light irradiation. Sample CuAuTiO2/ChTPP exhibited a maximum hydrogen generation of 1790 µmol g-1 h-1 under simulated sunlight irradiation, almost 12-folds higher compared with TiO2/ChTPP. Also, the nanocomposites revealed a similar tendency under visible light with a maximum hydrogen production of 590 µmol g-1 h-1. These results agree with the efficiency of photoinduced charge separation revealed by transient photocurrent and EIS.

Asunto(s)

Quitosano , Cobre , Hidrogeles , Hidrógeno , Luz Solar , Titanio , Quitosano/química , Titanio/química , Catálisis , Hidrógeno/química , Cobre/química , Hidrogeles/química , Oro/química , Procesos Fotoquímicos , Nanocompuestos/química , Nanopartículas del Metal/química

RESUMEN

3D-printed hydrogel scaffolds biomimicking the extracellular matrix (ECM) are key in cartilage tissue engineering as they can enhance the chondrogenic differentiation of mesenchymal stem cells (MSCs) through the presence of active nanoparticles such as graphene oxide (GO). Here, biomimetic hydrogels were developed by cross-linking alginate, gelatin, and chondroitin sulfate biopolymers in the presence of GO as a bioactive filler, with excellent processability for developing bioactive 3D printed scaffolds and for the bioprinting process. A novel bioink based on our hydrogel with embedded human MSCs presented a cell survival rate near 100% after the 3D bioprinting process. The effects of processing and filler concentration on cell differentiation were further quantitatively evaluated. The nanocomposited hydrogels render high MSC proliferation and viability, exhibiting intrinsic chondroinductive capacity without any exogenous factor when used to print scaffolds or bioprint constructs. The bioactivity depended on the GO concentration, with the best performance at 0.1 mg mL-1. These results were explained by the rational combination of the three biopolymers, with GO nanoparticles having carboxylate and sulfate groups in their structures, therefore, biomimicking the highly negatively charged ECM of cartilage. The bioactivity of this biomaterial and its good processability for 3D printing scaffolds and 3D bioprinting techniques open up a new approach to developing novel biomimetic materials for cartilage repair.

Asunto(s)

Alginatos , Bioimpresión , Diferenciación Celular , Condrogénesis , Sulfatos de Condroitina , Gelatina , Hidrogeles , Células Madre Mesenquimatosas , Nanocompuestos , Impresión Tridimensional , Andamios del Tejido , Humanos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacología , Alginatos/química , Alginatos/farmacología , Gelatina/química , Bioimpresión/métodos , Diferenciación Celular/efectos de los fármacos , Condrogénesis/efectos de los fármacos , Nanocompuestos/química , Andamios del Tejido/química , Hidrogeles/química , Hidrogeles/farmacología , Ingeniería de Tejidos/métodos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Grafito/química , Grafito/farmacología , Proliferación Celular/efectos de los fármacos , Células Cultivadas

RESUMEN

Staphylococcus aureus is a pathogen widely involved in wound infection due to its ability to release several virulence factors that impair the skin healing process, as well as its mechanism of drug resistance. Herein, sodium alginate and chitosan were combined to produce a hydrogel for topical delivery of neomycin to combat S. aureus associated with skin complications. The hydrogel was formulated by combining sodium alginate (50 mg/mL) and chitosan (50 mg/mL) solutions in a ratio of 9:1 (HBase). Neomycin was added to HBase to achieve a concentration of 0.4 mg/mL (HNeo). The incorporation of neomycin into the product was confirmed by scanning electron microscopy, FTIR and TGA analysis. The hydrogels produced are homogeneous, have a high swelling capacity, and show biocompatibility using erythrocytes and fibroblasts as models. The formulations showed physicochemical and pharmacological stability for 60 days at 4 ± 2 °C. HNeo totally inhibited the growth of S. aureus after 4 h. The antimicrobial effects were confirmed using ex vivo (porcine skin) and in vivo (murine) wound infection models. Furthermore, the HNeo-treated mice showed lower severity scores than those treated with HBase. Taken together, the obtained results present a new low-cost bioproduct with promising applications in treating infected wounds.

Asunto(s)

Alginatos , Antibacterianos , Quitosano , Hidrogeles , Neomicina , Staphylococcus aureus , Quitosano/química , Quitosano/farmacología , Alginatos/química , Alginatos/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Staphylococcus aureus/efectos de los fármacos , Animales , Ratones , Neomicina/farmacología , Neomicina/química , Neomicina/administración & dosificación , Antibacterianos/farmacología , Antibacterianos/química , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Infecciones Cutáneas Estafilocócicas/microbiología , Infecciones Cutáneas Estafilocócicas/patología , Portadores de Fármacos/química , Piel/efectos de los fármacos , Piel/microbiología

RESUMEN

Hydrogels based on natural polysaccharides have demonstrated efficacy in epithelial recovery from cutaneous burn wounds. Here, we prepared a double-network hydrogel consisting of galactomannan (from Cassia grandis seeds) and κ-carrageenan (commercially sourced), cross-linked with CaCl2, as a matrix for immobilizing lactoferrin and/or Cramoll, aiming at its applicability as dressings for second-degree burn wounds. The formulations obtained [H - hydrogel, HL - hydrogel + lactoferrin, HC - hydrogel + Cramoll and HLC - hydrogel + lactoferrin + Cramoll] were analyzed rheologically as well as in terms of their stability (pH, color, microbial contamination) for 90 days. The burn was created with an aluminum bar (97 ± 3 °C) in the dorsal region of Wistar rats and subsequently treated with hydrogels (H, HL, HC, HLC) and control saline solution (S). The burn was monitored for 3, 7 and 14 days to evaluate the efficacy of the hydrogels in promoting wound healing. The hydrogels did not reveal significant pH or microbiological changes; there was an increase in brightness and a reduction in opacity for H. The rheological analysis confirmed the gel-like viscoelastic signature of the systems without substantial modification of the basic rheological characteristics, however HLC proved to be more rigid, due to rheological synergy when combining protein biomolecules. Macroscopic analyses confirmed centripetal healing with wound contraction: S < H < HC < HL < HLC. Histopathological analyses showed that hydrogel-treated groups reduced inflammation, tissue necrosis and fibrosis, while promoting re-epithelialization with focal acanthosis, especially in HLC due to a positive synergistic effect, indicating its potential as a promising therapy in the repair of burns.

Asunto(s)

Quemaduras , Carragenina , Galactosa , Hidrogeles , Mananos , Ratas Wistar , Cicatrización de Heridas , Hidrogeles/química , Mananos/química , Mananos/farmacología , Animales , Quemaduras/terapia , Quemaduras/tratamiento farmacológico , Carragenina/química , Cicatrización de Heridas/efectos de los fármacos , Ratas , Galactosa/análogos & derivados , Galactosa/química , Masculino , Lactoferrina/química , Reología

RESUMEN

In situ forming hydrogels are promising for biomedical applications, especially in drug delivery. The precursor solution can be injected at the target site, where it undergoes a sol-gel transition to afford a hydrogel. In this sense, the most significant characteristic of these hydrogels is fast gelation behavior after injection. This study describes an all-polysaccharide, rapidly in situ-forming hydrogel composed of carboxymethyl chitosan (CMCHT) and hydroxyethyl cellulose functionalized with aldehyde groups (HEC-Ald). The HEC-Ald was synthesized through acetal functionalization, followed by acid deprotection. This innovative approach avoids cleavage of pyran rings, as is inherent in the periodate oxidation approach, which is the most common method currently employed for adding aldehyde groups to polysaccharides. The resulting hydrogel exhibited fast stress relaxation, self-healing properties, and pH sensitivity, which allowed it to control the release of an encapsulated model drug in response to the medium pH. Based on the collected data, the HEC-Ald/CMCHT hydrogels show promise as pH-sensitive drug carriers.

Asunto(s)

Aldehídos , Celulosa , Celulosa/análogos & derivados , Quitosano , Quitosano/análogos & derivados , Hidrogeles , Quitosano/química , Concentración de Iones de Hidrógeno , Celulosa/química , Hidrogeles/química , Aldehídos/química , Portadores de Fármacos/química , Liberación de Fármacos , Polisacáridos/química