RESUMEN
The purpose of this study is to design and evaluate a series of porous hydrogels by considering three independent variables using the Box-Behnken method. Accordingly, concentrations of the constituent macromolecules of the hydrogels, Polyvinyl Alcohol and Gelatin, and concentration of the crosslinking agent are varied to fabricate sixteen different porous samples utilizing the lyophilization process. Subsequently, the porous hydrogels are subjected to a battery of tests, including Fourier Transform Infrared spectroscopy, morphology assessment, pore-size study, porosimetry, uniaxial compression, and swelling measurements. Additionally, in-vitro cell assessments are performed by culturing mouse fibroblast cells (L-929) on the hydrogels, where viability, proliferation, adhesion, and morphology of the L-929 cells are monitored over 24, 48, and 72 h to evaluate the biocompatibility of these biomaterials. To better understand the mechanical behavior of the hydrogels under compressive loadings, Deep Neural Networks (DNNs) are implemented to predict and capture their compressive stress-strain responses as a function of the constituent materials' concentrations and duration of the performed mechanical tests. Overall, this study emphasizes the importance of considering multiple variables in the design of porous hydrogels, provides a comprehensive evaluation of their mechanical and biological properties, and, particularly, implements DNNs in the prediction of the hydrogels' stress-strain responses.
Asunto(s)
Materiales Biocompatibles , Gelatina , Ratones , Animales , Gelatina/química , Porosidad , Materiales Biocompatibles/química , Alcohol Polivinílico/química , Hidrogeles/química , Aprendizaje Automático SupervisadoRESUMEN
In this work, a series of new biodegradable and biocompatible hydrogels were synthesized by photopolymerization of dextran-methacrylate (DXM) with poly(ethylene glycol)-maleic acid copolymer (poly(PEG-co-MA, PEGMA)) using (-)-riboflavin as a visible light photoinitiator and L-arginine as a co-photoinitiator. DXM was prepared by acylation of dextran (DX) with methacryloyl chloride (MAC), and PEGMA was synthesized by polycondensation of poly(ethylene glycol) (PEG) and maleic acid (MA). The DXM and PEGMA were characterized by FT-IR and 1HNMR spectroscopy. Different types of hydrogels from various ratios of DXM and PEGMA were prepared and characterized by SEM. The results showed that the prepared hydrogel by photo-cross-linking of DXM (DPHG0) was transparent and flexible, and its physical shape was excellent, but it was sticky. The stickiness was reduced by increasing the PEGMA contents, and different types of DXM/PEGMA hydrogels (DPHG1-4) with various properties were prepared. For example, DPHG2 (PEGMA content was 0.25 g) was transparent and flexible, its physical shape was excellent, and it was not sticky. The prepared hydrogels showed excellent cytocompatibility, and their tensile and compressive strength were also evaluated. Additionally, the in vitro degradation and swelling ratios of the prepared hydrogels were studied in buffer solution at different pHs.
Asunto(s)
Hidrogeles , Polietilenglicoles , Polietilenglicoles/química , Hidrogeles/química , Dextranos/química , Espectroscopía Infrarroja por Transformada de Fourier , Materiales Biocompatibles/química , Polímeros/química , Metacrilatos/química , LuzRESUMEN
The use of hydrogels as scaffolds for three-dimensional (3D) cell growth is an active area of research in tissue engineering. Herein, we report the self-assembly of an ultrashort peptide, a tetrapeptide, Asp-Leu-IIe-IIe, the shortest peptide sequence from a highly fibrillogenic protein TDP-43, into the hydrogel. The hydrogel was mechanically strong and highly stable, with storage modulus values in MPa ranges. The hydrogel supported the proliferation and successful differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) in its matrix as assessed by cell viability, calcium deposition, alkaline phosphatase (ALP) activity, and the expression of osteogenic marker gene studies. To check whether the hydrogel supports 3D growth and regeneration in in vivo conditions, a rabbit critical bone defect model was used. Micro-computed tomography (CT) and X-ray analysis demonstrated the formation of mineralized neobone in the defect areas, with significantly higher bone mineralization and relative bone densities in animals treated with the peptide hydrogel compared to nontreated and matrigel treatment groups. The ultrashort peptide-based hydrogel developed in this work holds great potential for its further development as tissue regeneration and/or engineering scaffolds.
Asunto(s)
Densidad Ósea , Hidrogeles , Animales , Conejos , Hidrogeles/farmacología , Microtomografía por Rayos X , Péptidos/farmacologíaRESUMEN
In the study, fabrication of Arabic gum (AG) hydrogels via reverse micellization method is reported. AG hydrogels were utilized as capping agents to encapsulate zinc sulphide (ZnS), and cadmium sulphide (CdS) nanoparticles via in-situ reduction. Pristine and nanocomposite hydrogels (AG-ZnS and AG-CdS) were characterized through SEM, EDX, TEM, XRD, FTIR, TGA, UV/Visible, and photoluminescence spectroscopy. The hydrogels were subjected to multiple biological assays including antimicrobial, antioxidant, and anti-diabetic formulation, in addition to biocompatibility test. The hydrogels were found to be more effective against bacterial and fungal strains. For instance, AG-ZnS exhibited excellent growth inhibition activity against Escherichia coli (ZoI: 12 ± 1.04 mm) and Candida albicans (35 ± 0.94 mm). Likewise, the nanocomposites hydrogel also displayed excellent DPPH and ABTS free radical scavenging capacity, total antioxidant capacity (TAC), and total reducing power (TRP) ability. Among the hydrogels, AG-ZnS demonstrated considerable α-amylase, and α-glucosidase inhibition potential. Above all, the hydrogels were found highly compatible with human red blood cells (hRBCs). Owing to remarkable antioxidant, antibacterial, antifungal, and bio-compatible nature, the fabricated nanocomposites hydrogels have the potential to be explored in tissue engineering, wound healing, drug delivery, and in environmentally friendly hygiene products.
Asunto(s)
Nanopartículas del Metal , Nanocompuestos , Antibacterianos/química , Antibacterianos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Escherichia coli , Humanos , Hidrogeles/química , Nanopartículas del Metal/química , Nanocompuestos/química , Nanogeles , Plata/químicaRESUMEN
The mechanoregulated proteins YAP/TAZ are involved in the adipogenic/osteogenic switch of mesenchymal stem cells (MSCs). MSC fate decision can be unbalanced by controlling substrate mechanics, in turn altering the transmission of tension through cell cytoskeleton. MSCs have been proposed for orthopedic and reconstructive surgery applications. Thus, a tight control of their adipogenic potential is required in order to avoid their drifting towards fat tissue. Substrate mechanics has been shown to drive MSC commitment and to regulate YAP/TAZ protein shuttling and turnover. The mechanism by which YAP/TAZ co-transcriptional activity is mechanically regulated during MSC fate acquisition is still debated. Here, we design few bioengineering tools suited to disentangle the contribution of mechanical from biological stimuli to MSC adipogenesis. We demonstrate that the mechanical repression of YAP happens through its phosphorylation, is purely mediated by cell spreading downstream of substrate mechanics as dictated by dimensionality. YAP repression is sufficient to prompt MSC adipogenesis, regardless of a permissive biological environment, TEAD nuclear presence or focal adhesion stabilization. Finally, by harnessing the potential of YAP mechanical regulation, we propose a practical example of the exploitation of adipogenic transdifferentiation in tumors.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adipogénesis , Movimiento Celular , Factores de Transcripción/metabolismo , Actinas/metabolismo , Adipocitos/metabolismo , Tejido Adiposo/citología , Línea Celular Tumoral , Núcleo Celular/metabolismo , Proliferación Celular , Reprogramación Celular , Matriz Extracelular/metabolismo , Adhesiones Focales/metabolismo , Humanos , Fosforilación , Transcripción Genética , Proteínas Señalizadoras YAPRESUMEN
The study is focused on formulation of biocompatible hydrogels with a poorly soluble drug ibuprofen (5%) and comprehensive evaluation and comparison of effect of different bioadhesive polymers on their suitability for application on skin, physical stability during the accelerated and natural aging tests (by performing centrifugation test, light microscopy, differential scanning calorimetry, rheological and pH measurements), and in vitro drug release kinetics. Hydrogels, formulated with xanthan gum 1% (XIB), sodium carboxymethylcellulose 5% (CMCIB), poloxamer 407 16% (PIB), and carbomer 1% (KIB), were soft pseudoplastic semisolids with thixotropy and biocompatible pH. The type of the polymer significantly affected apparent viscosity of the hydrogels and miscibility rate with artificial sweat, their physical stability, and shape, size, and aggregation of the drug crystals and degree of crystallization. The drug release in all investigated hydrogels was diffusion-controlled in accordance with the Higuchi model and sustained for 12 h, with the drug release rate and the amount of drug released depended on the polymer. The described formulation approach enabled discrimination of the hydrogels with unsatisfactory application properties (CMCIB) and physical stability (KIB), and selection of the hydrogel with promising characteristics in terms of all investigated aspects (XIB) which could be considered for further evaluation.