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1.
J Mol Cell Cardiol ; 182: 75-85, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37482238

RESUMEN

Cardiovascular disease is the leading cause of mortality and morbidity worldwide. Despite improvements in the standard of care for patients with heart diseases, including innovation in pharmacotherapy and surgical interventions, none have yet been proven effective to prevent the progression to heart failure. Cardiac transplantation is the last resort for patients with severe heart failure, but donor shortages remain a roadblock. Cardiac regenerative strategies include cell-based therapeutics, gene therapy, direct reprogramming of non-cardiac cells, acellular biologics, and tissue engineering methods to restore damaged hearts. Significant advancements have been made over the past several decades within each of these fields. This review focuses on the advancements of: 1) cell-based cardiac regenerative therapies, 2) the use of noncoding RNA to induce endogenous cell proliferation, and 3) application of bioengineering methods to promote retention and integration of engrafted cells. Different cell sources have been investigated, including adult stem cells derived from bone marrow and adipose cells, cardiosphere-derived cells, skeletal myoblasts, and pluripotent stem cells. In addition to cell-based transplantation approaches, there have been accumulating interest over the past decade in inducing endogenous CM proliferation for heart regeneration, particularly with the use of noncoding RNAs such as miRNAs and lncRNAs. Bioengineering applications have focused on combining cell-transplantation approaches with fabrication of a porous, vascularized scaffold using biomaterials and advanced bio-fabrication techniques that may offer enhanced retention of transplanted cells, with the hope that these cells would better engraft with host tissue to improve cardiac function. This review summarizes the present status and future challenges of cardiac regenerative therapies.


Asunto(s)
Enfermedades Cardiovasculares , Cardiopatías , Insuficiencia Cardíaca , Adulto , Humanos , Miocitos Cardíacos/trasplante , Trasplante de Células Madre/métodos , Cardiopatías/genética
2.
Adv Healthc Mater ; 12(18): e2203233, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36929644

RESUMEN

Managing slow-healing wounds and associated complications is challenging, time-consuming, and expensive. Systematic collection, analysis, and dissemination of correct wound status data are critical for enhancing healing outcomes and reducing complications. However, traditional data collection approaches are often neither accurate nor user-friendly and require diverse skill levels, resulting in the collection of inconsistent and unreliable data. As an advancement to the authors' previously developed hydrogel-based smart wound dressing, here is reported an enhanced integration of drug delivery and sensing (pH and glucose) modules for accelerated treatment and continuous monitoring of cutaneous wounds. In the current study, growth factor delivery modules and an array of colorimetric glucose sensors are incorporated into the dressing to promote wound healing and extend the dressing's utility for diabetic wound treatment. Furthermore, the efficacy of the wound dressing in monitoring infection and supporting wound healing via antibiotic and growth factor delivery is investigated in mice models. The updated dressing reveals excellent healing benefits on non-infected and infected wounds, as well as real-time monitoring and early detection of wound infection.


Asunto(s)
Vendajes , Traumatismos de los Tejidos Blandos , Infección de la Herida Quirúrgica , Animales , Ratones , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Traumatismos de los Tejidos Blandos/terapia , Infección de la Herida Quirúrgica/terapia
3.
Am Heart J Plus ; 27: 100279, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38511100

RESUMEN

Introduction: Abdominal Aortic Aneurysm (AAA) is a highly morbid condition and is the 11th leading cause of death in the United States. Treatment options are limited to operative interventions, with minimal non-operative options. Prior literature has demonstrated a benefit to the use of mesenchymal stem cells (MSCs) in attenuating AAA formation. We demonstrate the utility of MSCs in treating AAA in swine, focusing on the mechanical and structural characteristics of aortic tissue after treatment. Methods: 16 Yorkshire pigs underwent retroperitoneal exposure of the infrarenal aorta, with subsequent induction of AAA with peri-adventitial elastase and collagenase. A 1 × 4 cm piece of Gelfoam, an absorbable gelatin-based hemostatic agent, was soaked in media or human MSCs and placed directly on the vessel for control and experimental animals. At postoperative day 21, animals were sacrificed and the infrarenal aorta at this location was harvested for analysis. Tensile strength was measured using a tensiometer, from which Young's modulus and maximum strain were calculated. Results: All animals survived the surgery and post-operative course. Young's elastic modulus for the aneurysm control group was 15.83 ± 1.61 compared to 22.13 ± 2.34 for the stem cell treated segment, p = 0.0316. There was no significant difference in the peak stress between groups. Conclusions: This is the first study to demonstrate the mechanical effects of stem cell therapy on a model of AAA in swine. Young's modulus, which characterizes the intrinsic capacity of a tissue to withstand stress, was greater in the animals treated with MSCs compared to control animals with aneurysms. This methodology can be utilized in future large animal models to develop cell and drug-based therapies for AAA.

4.
Biomolecules ; 12(12)2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36551224

RESUMEN

A heterogenous Palladium anchored Resorcinol-formaldehyde-hyperbranched PEI mesoporous catalyst, made by one-pot synthesis, was used successfully for in situ Suzuki-Miyaura cross coupling synthesis of anticancer prodrug PP-121 from iodoprazole and boronic ester precursors. The mesoporous catalyst with the non-cytotoxic precursors were tested in 2D in vitro model with excellent cytocompatibility and a strong suppression of PC3 cancer cell proliferation, underscored by 50% reduction in PC3 cells viability and 55% reduction in cell metabolism activity and an enhanced rate of early and late apoptosis in flow cytometry, that was induced only by successful in situ pro drug PP121 synthesis from the precursors. The 3D gelatin methacrylate hydrogel encapsulated in vitro cell models underscored the results with a 52% reduction in cell metabolism and underscored apoptosis of PC3 cells when the Pd anchored catalyst was combined with the precursors. In situ application of Suzuki-Miyaura cross coupling of non-cytotoxic precursors to cancer drug, along with their successful encapsulation in an injectable hydrogel could be applied for tumor point drug delivery strategies that can circumvent deleterious side effects and poor bioavailability chemotherapy routes with concomitant enhanced efficacy.


Asunto(s)
Hidrogeles , Paladio , Hidrogeles/farmacología , Catálisis , Paladio/farmacología
5.
Sci Rep ; 12(1): 11451, 2022 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-35794165

RESUMEN

AMPylation is an emerging post-translational modification that occurs on the hydroxyl group of threonine, serine, or tyrosine via a phosphodiester bond. AMPylators catalyze this process as covalent attachment of adenosine monophosphate to the amino acid side chain of a peptide. Recent studies have shown that this post-translational modification is directly responsible for the regulation of neurodevelopment and neurodegeneration and is also involved in many physiological processes. Despite the importance of this post-translational modification, there is no peptide sequence dataset available for conducting computation analysis. Therefore, so far, no computational approach has been proposed for predicting AMPylation. In this study, we introduce a new dataset of this distinct post-translational modification and develop a new machine learning tool using a deep convolutional neural network called DeepAmp to predict AMPylation sites in proteins. DeepAmp achieves 77.7%, 79.1%, 76.8%, 0.55, and 0.85 in terms of Accuracy, Sensitivity, Specificity, Matthews Correlation Coefficient, and Area Under Curve for AMPylation site prediction task, respectively. As the first machine learning model, DeepAmp demonstrate promising results which highlight its potential to solve this problem. Our presented dataset and DeepAmp as a standalone predictor are publicly available at https://github.com/MehediAzim/DeepAmp .


Asunto(s)
Aprendizaje Automático , Redes Neurales de la Computación , Secuencia de Aminoácidos , Aminoácidos , Procesamiento Proteico-Postraduccional
6.
Mater Today Bio ; 13: 100199, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35028556

RESUMEN

Controlling bleeding from a raptured tissue, especially during the surgeries, is essentially important. Particularly for soft and dynamic internal organs where use of sutures, staples, or wires is limited, treatments with hemostatic adhesives have proven to be beneficial. However, major drawbacks with clinically used hemostats include lack of adhesion to wet tissue and poor mechanics. In view of these, herein, we engineered a double-crosslinked sealant which showed excellent hemostasis (comparable to existing commercial hemostat) without compromising its wet tissue adhesion. Mechanistically, the engineered hydrogel controlled the bleeding through its wound-sealing capability and inherent chemical activity. This mussel-inspired hemostatic adhesive hydrogel, named gelatin methacryloyl-catechol (GelMAC), contained covalently functionalized catechol and methacrylate moieties and showed excellent biocompatibility both in vitro and in vivo. Hemostatic property of GelMAC hydrogel was initially demonstrated with an in vitro blood clotting assay, which showed significantly reduced clotting time compared to the clinically used hemostat, Surgicel®. This was further assessed with an in vivo liver bleeding test in rats where GelMAC hydrogel closed the incision rapidly and initiated blood coagulation even faster than Surgicel®. The engineered GelMAC hydrogel-based seaalant with excellent hemostatic property and tissue adhesion can be utilized for controlling bleeding and sealing of soft internal organs.

7.
Adv Funct Mater ; 31(42)2021 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-34924912

RESUMEN

Bioengineering of tissues and organs has the potential to generate functional replacement organs. However, achieving the full-thickness vascularization that is required for long-term survival of living implants has remained a grand challenge, especially for clinically sized implants. During the pre-vascular phase, implanted engineered tissues are forced to metabolically rely on the diffusion of nutrients from adjacent host-tissue, which for larger living implants results in anoxia, cell death, and ultimately implant failure. Here it is reported that this challenge can be addressed by engineering self-oxygenating tissues, which is achieved via the incorporation of hydrophobic oxygen-generating micromaterials into engineered tissues. Self-oxygenation of tissues transforms anoxic stresses into hypoxic stimulation in a homogenous and tissue size-independent manner. The in situ elevation of oxygen tension enables the sustained production of high quantities of angiogenic factors by implanted cells, which are offered a metabolically protected pro-angiogenic microenvironment. Numerical simulations predict that self-oxygenation of living tissues will effectively orchestrate rapid full-thickness vascularization of implanted tissues, which is empirically confirmed via in vivo experimentation. Self-oxygenation of tissues thus represents a novel, effective, and widely applicable strategy to enable the vascularization living implants, which is expected to advance organ transplantation and regenerative medicine applications.

8.
J Surg Res ; 268: 79-86, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34289418

RESUMEN

INTRODUCTION: Producing a reliable large-animal model of AAA has proven challenging. We sought to create a reproducible swine model of AAA using enzymatic degradation of the aortic wall. METHODS: Twelve male Yorkshire swine received periadventitial injections of type 1 collagenase and porcine pancreatic elastase into a 4 cm segment of infrarenal aorta. Nine survived until postoperative day (POD) 21. Aortic growth was monitored at 7 and 14 days using ultrasound. The animals were euthanized on POD 21, and the suprarenal (control) and infrarenal aorta were harvested for analysis, after gross measurement of aortic diameter (AD). Tensile strength was measured and additional segments were collected for histopathological analysis. PCR of matrix metalloproteinases (MMP9) was conducted. Groups were compared with paired t-tests, or ANOVA, where appropriate. RESULTS: Average percent growth of AD at POD 21 for treated segments was 27% versus 4.5% for control tissue. The average difference in AD by subject, was 26.7% (P<0.001). Aortic medial thickness was decreased in treated tissue; 235 µm versus 645 µm (P<0.0001). Quantities of both medial elastin fibers, and smooth muscles cells were decreased in treated tissue; 1.8% compared to 9.9% (P<0.0001), and 24% versus 37.4%, respectively. Tensile strength was also decreased in treated tissue; 16.7 MPa versus 29.5 MPa (P=0.0002). A 12-fold increase in expression of MMP9 mRNA was also demonstrated in aneurysmal tissue (P=0.002) CONCLUSION: A reproducible, large-animal model of AAA, with anatomical, histopathological, and biomechanical properties that are clinically translatable, can be achieved with extraluminal enzymatic degradation.


Asunto(s)
Aneurisma de la Aorta Abdominal , Animales , Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/metabolismo , Modelos Animales de Enfermedad , Masculino , Miocitos del Músculo Liso/patología , Elastasa Pancreática/metabolismo , Porcinos
9.
Molecules ; 26(7)2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33807301

RESUMEN

To address the issue of global warming and climate change issues, recent research efforts have highlighted opportunities for capturing and electrochemically converting carbon dioxide (CO2). Despite metal doped polymers receiving widespread attention in this respect, the structures hitherto reported lack in ease of synthesis with scale up feasibility. In this study, a series of mesoporous metal-doped polymers (MRFs) with tunable metal functionality and hierarchical porosity were successfully synthesized using a one-step copolymerization of resorcinol and formaldehyde with Polyethyleneimine (PEI) under solvothermal conditions. The effect of PEI and metal doping concentrations were observed on physical properties and adsorption results. The results confirmed the role of PEI on the mesoporosity of the polymer networks and high surface area in addition to enhanced CO2 capture capacity. The resulting Cobalt doped material shows excellent thermal stability and promising CO2 capture performance, with equilibrium adsorption of 2.3 mmol CO2/g at 0 °C and 1 bar for at a surface area 675.62 m2/g. This mesoporous polymer, with its ease of synthesis is a promising candidate for promising for CO2 capture and possible subsequent electrochemical conversion.

10.
J Mech Behav Biomed Mater ; 110: 103960, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32957251

RESUMEN

Three-dimensional (3D) printing is an efficient technique for the fabrication of electronic devices. It also enables the use conductive of biomaterials in various applications, such as implants and flexible devices. Designing a new bioink is extremely challenging. For bioelectronics devices, bioink materials should be printable, flexible, conductive, harmless to cells, and sufficiently strong to maintain their shape when immersed in nutrients or under pressure. Over the past few years, several flexible conductive bioinks have been developed that are based on composite pastes containing a biopolymer and conductive micro- and nanoscale materials in the form of metallic particles, conducting polymers, or a mixture of them. Herein, we report a new strategy for the fabrication of a bioink for a commercial 3D printer with the desired conductivity, mechanical properties, and biocompatibility, using a poly(glycerol-co-sebacate) (PGS)-based polymer and zinc. The PGS-based polymer and lithium phenyl-2,4,6-trimethylbenzoylphosphinate (as a photoinitiator) were added to the zinc, and then, the prepared bioink was polymerized during 3D printing under visible light. According to a microstructural investigation using scanning electron microscopy, the zinc particles were homogeneously distributed in the PGSA matrix. The conductivity of bioink increases with chemical sintering and with an increase in the amount of zinc particles. Based on rheology tests, the appropriate printable composition is 60% zinc and 40% PGS-based polymer. This bioink exhibited remarkable mechanical and adhesive properties in comparison with the PGS-based polymer without zinc, according to tensile, compression, lap shear, wound closure, and burst pressure modules. In vitro and in vivo results indicated that the bioink was not toxic to the cells or the animal over a period of culturing.


Asunto(s)
Tinta , Impresión Tridimensional , Animales , Conductividad Eléctrica , Electrónica , Reología
11.
ACS Appl Mater Interfaces ; 11(42): 38373-38384, 2019 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-31523968

RESUMEN

Adhesion to wet and dynamic surfaces is vital for many biomedical applications. However, the development of effective tissue adhesives has been challenged by the required combination of properties, which includes mechanical similarity to the native tissue, high adhesion to wet surfaces, hemostatic properties, biodegradability, high biocompatibility, and ease of use. In this study, we report a novel bioinspired design with bioionic liquid (BIL) conjugated polymers to engineer multifunctional highly sticky, biodegradable, biocompatible, and hemostatic adhesives. Choline-based BIL is a structural precursor of the phospholipid bilayer in the cell membrane. We show that the conjugation of choline molecules to naturally derived polymers (i.e., gelatin) and synthetic polymers (i.e., polyethylene glycol) significantly increases their adhesive strength and hemostatic properties. Synthetic or natural polymers and BILs were mixed at room temperature and cross-linked via visible light photopolymerization to make hydrogels with tunable mechanical, physical, adhesive, and hemostatic properties. The hydrogel adhesive exhibits a close to 50% decrease in the total blood volume loss in tail cut and liver laceration rat animal models compared to the control. This technology platform for adhesives is expected to have further reaching application vistas from tissue repair to wound dressings and the attachment of flexible electronics.


Asunto(s)
Hidrogeles/química , Adhesivos Tisulares/química , Heridas y Lesiones/terapia , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/uso terapéutico , Línea Celular , Supervivencia Celular/efectos de los fármacos , Colina/química , Modelos Animales de Enfermedad , Hidrogeles/farmacología , Hidrogeles/uso terapéutico , Concentración de Iones de Hidrógeno , Hidrólisis , Luz , Hígado/efectos de los fármacos , Hígado/lesiones , Hígado/patología , Ratones , Polietilenglicoles/química , Polímeros/química , Ratas , Resistencia al Corte , Porcinos , Adhesivos Tisulares/farmacología , Adhesivos Tisulares/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos
12.
ACS Biomater Sci Eng ; 4(7): 2528-2540, 2018 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-33435116

RESUMEN

Hydrogel-based biomaterials have been widely used for tissue engineering applications because of their high water content, swellability, and permeability, which facilitate transport and diffusion of essential nutrients, oxygen, and waste across the scaffold. These characteristics make hydrogels suitable for encapsulating cells and creating a cell supportive environment that promotes tissue regeneration when implanted in vivo. This is particularly important in the context of tissues whose intrinsic regenerative capacity is limited, such as cartilage. However, the clinical translation of hydrogels has been limited by their poor mechanical performance, low adhesive strength, uncontrolled degradation rates, and their susceptibility to bacterial colonization. Here, we introduce an elastic, antimicrobial, and adhesive hydrogel comprised of methacrylated hyaluronic acid (MeHA) and an elastin-like polypeptide (ELP), which can be rapidly photo-cross-linked in situ for the regeneration and repair of different tissues. Hybrid hydrogels with a wide range of physical properties were engineered by varying the concentrations of MeHA and ELP. In addition, standard adhesion tests demonstrated that the MeHA/ELP hydrogels exhibited higher adhesive strength to the tissue than commercially available tissue adhesives. MeHA/ELP hydrogels were then rendered antimicrobial through the incorporation of zinc oxide (ZnO) nanoparticles, and were shown to significantly inhibit the growth of methicillin-resistant Staphylococcus aureus (MRSA), as compared to controls. Furthermore, the composite adhesive hydrogels supported in vitro mammalian cellular growth, spreading, and proliferation. In addition, in vivo subcutaneous implantation demonstrated that MeHA/ELP hydrogels did not elicit any significant inflammatory response, and could be efficiently biodegraded while promoting the integration of new autologous tissue. In summary, we demonstrated for the first time that MeHA/ELP-ZnO hydrogel can be used as an adhesive and antimicrobial biomaterial for tissue engineering applications, because of its highly tunable physical characteristics, as well as remarkable adhesive and antimicrobial properties.

13.
J Mech Behav Biomed Mater ; 77: 360-374, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28985616

RESUMEN

This study was aimed to improve of the corrosion resistance and mechanical properties of Mg/15TiO2/5HA nanocomposite by silicon and magnesium oxide coatings prepared using a powder metallurgy method. The phase evolution, chemical composition, microstructure and mechanical properties of uncoated and coated samples were characterized. Electrochemical and immersion tests used to investigate the in vitro corrosion behavior of the fabricated samples. The adhesion strength of ~36MPa for MgO and ~32MPa for Si/MgO coatings to substrate was measured by adhesion test. Fabrication a homogenous double layer coating with uniform thicknesses consisting micro-sized particles of Si as outer layer and flake-like particles of MgO as the inner layer on the surface of Mg/15TiO2/5HA nanocomposite caused the corrosion resistance and ductility increased whereas the ultimate compressive stress decreased. However, after immersion in SBF solution, Si/MgO-coated sample indicates the best mechanical properties compared to those of the uncoated and MgO-coated samples. The increase of cell viability percentage of the normal human osteoblast (NHOst) cells indicates the improvement in biocompatibility of Mg/15TiO2/5HA nanocomposite by Si/MgO coating.


Asunto(s)
Aleaciones/química , Materiales Biocompatibles Revestidos/química , Durapatita/química , Óxido de Magnesio/química , Nanocompuestos/química , Osteoblastos/efectos de los fármacos , Resorción Ósea , Adhesión Celular , Supervivencia Celular , Fuerza Compresiva , Corrosión , Electroquímica , Humanos , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Potenciometría , Presión , Silicio , Solubilidad , Estrés Mecánico , Propiedades de Superficie , Temperatura , Resistencia a la Tracción , Titanio , Difracción de Rayos X
14.
Mater Sci Eng R Rep ; 119: 1-35, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29200661

RESUMEN

Recent years have seen tremendous advances in the field of hydrogel-based biomaterials. One of the most prominent revolutions in this field has been the integration of elements or techniques that enable spatial and temporal control over hydrogels' properties and functions. Here, we critically review the emerging progress of spatiotemporal control over biomaterial properties towards the development of functional engineered tissue constructs. Specifically, we will highlight the main advances in the spatial control of biomaterials, such as surface modification, microfabrication, photo-patterning, and three-dimensional (3D) bioprinting, as well as advances in the temporal control of biomaterials, such as controlled release of molecules, photocleaving of proteins, and controlled hydrogel degradation. We believe that the development and integration of these techniques will drive the engineering of next-generation engineered tissues.

15.
Biomater Sci ; 5(10): 2093-2105, 2017 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-28805830

RESUMEN

Photocrosslinkable materials have been frequently used for constructing soft and biomimetic hydrogels for tissue engineering. Although ultraviolet (UV) light is commonly used for photocrosslinking such materials, its use has been associated with several biosafety concerns such as DNA damage, accelerated aging of tissues, and cancer. Here we report an injectable visible light crosslinked gelatin-based hydrogel for myocardium regeneration. Mechanical characterization revealed that the compressive moduli of the engineered hydrogels could be tuned in the range of 5-56 kPa by changing the concentrations of the initiator, co-initiator and co-monomer in the precursor formulation. In addition, the average pore sizes (26-103 µm) and swelling ratios (7-13%) were also shown to be tunable by varying the hydrogel formulation. In vitro studies showed that visible light crosslinked GelMA hydrogels supported the growth and function of primary cardiomyocytes (CMs). In addition, the engineered materials were shown to be biocompatible in vivo, and could be successfully delivered to the heart after myocardial infarction in an animal model to promote tissue healing. The developed visible light crosslinked hydrogel could be used for the repair of various soft tissues such as the myocardium and for the treatment of cardiovascular diseases with enhanced therapeutic functionality.


Asunto(s)
Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Gelatina/química , Gelatina/farmacología , Hidrogeles/química , Luz , Procesos Fotoquímicos , Animales , Caprolactama/química , Proliferación Celular/efectos de los fármacos , Masculino , Ensayo de Materiales , Fenómenos Mecánicos , Ratones , Miocitos Cardíacos/citología , Miocitos Cardíacos/efectos de los fármacos , Células 3T3 NIH , Polimerizacion , Ratas , Ratas Sprague-Dawley
16.
Sci Rep ; 7(1): 4345, 2017 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-28659629

RESUMEN

Conventional methods to engineer electroconductive hydrogels (ECHs) through the incorporation of conductive nanomaterials and polymers exhibit major technical limitations. These are mainly associated with the cytotoxicity, as well as poor solubility, processability, and biodegradability of their components. Here, we describe the engineering of a new class of ECHs through the functionalization of non-conductive polymers with a conductive choline-based bio-ionic liquid (Bio-IL). Bio-IL conjugated hydrogels exhibited a wide range of highly tunable physical properties, remarkable in vitro and in vivo biocompatibility, and high electrical conductivity without the need for additional conductive components. The engineered hydrogels could support the growth and function of primary cardiomyocytes in both two dimentinal (2D) and three dimensional (3D) cultures in vitro. Furthermore, they were shown to be efficiently biodegraded and possess low immunogenicity when implanted subcutaneously in rats. Taken together, our results suggest that Bio-IL conjugated hydrogels could be implemented and readily tailored to different biomedical and tissue engineering applications.

17.
Biomaterials ; 140: 115-127, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28646685

RESUMEN

Conventional surgical techniques to seal and repair defects in highly stressed elastic tissues are insufficient. Therefore, this study aimed to engineer an inexpensive, highly adhesive, biocompatible, and biodegradable sealant based on a modified and naturally derived biopolymer, gelatin methacryloyl (GelMA). We tuned the degree of gelatin modification, prepolymer concentration, photoinitiator concentration, and crosslinking conditions to optimize the physical properties and adhesion of the photocrosslinked GelMA sealants. Following ASTM standard tests that target wound closure strength, shear resistance, and burst pressure, GelMA sealant was shown to exhibit adhesive properties that were superior to clinically used fibrin- and poly(ethylene glycol)-based glues. Chronic in vivo experiments in small as well as translational large animal models proved GelMA to effectively seal large lung leakages without the need for sutures or staples, presenting improved performance as compared to fibrin glue, poly(ethylene glycol) glue and sutures only. Furthermore, high biocompatibility of GelMA sealant was observed, as evidenced by a low inflammatory host response and fast in vivo degradation while allowing for adequate wound healing at the same time. Combining these results with the low costs, ease of synthesis and application of the material, GelMA sealant is envisioned to be commercialized not only as a sealant to stop air leakages, but also as a biocompatible and biodegradable hydrogel to support lung tissue regeneration.


Asunto(s)
Materiales Biocompatibles/química , Gelatina/química , Hidrogeles/química , Metacrilatos/química , Adhesivos Tisulares/química , Cicatrización de Heridas , Células 3T3 , Animales , Materiales Biocompatibles/uso terapéutico , Gelatina/uso terapéutico , Hidrogeles/uso terapéutico , Lesión Pulmonar/terapia , Masculino , Ensayo de Materiales , Metacrilatos/uso terapéutico , Ratones , Ratas Wistar , Porcinos , Resistencia a la Tracción , Adhesivos Tisulares/uso terapéutico
18.
Langmuir ; 32(44): 11573-11579, 2016 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-27797206

RESUMEN

Polycatalytic enzyme complexes made by immobilization of industrial enzymes on polymer- or nanoparticle-based scaffolds are technologically attractive due to their recyclability and their improved substrate binding and catalytic activities. Herein, we report the synthesis of polycatalytic complexes by the immobilization of nonprocessive cellulases on the surface of colloidal polymers with a magnetic nanoparticle core and the study of their binding and catalytic activities. These polycatalytic cellulase complexes have increased binding affinity for the substrate. But due to their larger size, these complexes were unable to access to the internal surfaces of cellulose and have significantly lower binding capacity when compared to those of the corresponding free enzymes. Analysis of released soluble sugars indicated that the formation of complexes may promote the prospect of having consistent, multiple attacks on cellulose substrate. Once bound to the substrate, polycatalytic complexes tend to remain on the surface with very limited mobility due to their strong, multivalent binding to cellulose. Hence, the overall performance of polycatalytic complexes is limited by its substrate accessibility as well as mobility on the substrate surface.


Asunto(s)
Celulasas/química , Celulosa/química , Enzimas Inmovilizadas/química , Proteínas Fúngicas/química , Nanopartículas de Magnetita/química , Ácidos Polimetacrílicos/química , Celobiosa/química , Coloides , Glucosa/química , Cinética , Nanopartículas de Magnetita/ultraestructura , Unión Proteica , Especificidad por Sustrato
19.
Nanotechnology ; 26(8): 085705, 2015 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-25656872

RESUMEN

Visible light active and stable nanoporous polymeric base-crystalline TiO2 nanocomposites were solvothermally synthesized from in situ copolymerization of divinylbenzene (DVB) with 1-vinylimidazolate (VI) or 4-vinylpyridine (Py) in the presence of tetrabutyl titanate without the use of any other additives (PDVB-VI-TiO2-x, PDVB-Py-TiO2-x, where x stands for the molar ratio of TiO2 to VI or Py), which showed excellent activity with respect to catalyzing the degradation of organic pollutants of p-nitrophenol (PNP) and rhodamine-B (RhB). TEM and SEM images show that PDVB-VI-TiO2-x and PDVB-Py-TiO2-x have abundant nanopores, and TiO2 nanocrystals with a high degree of crystallinity were homogeneously embedded in the PDVB-VI-TiO2-x and PDVB-Py-TiO2-x, forming a stable 'brick-and-mortar' nanostructure. PDVB-VI and PDVB-Py supports act as the glue linking TiO2 nanocrystals to form nanopores and constraining the agglomeration of TiO2 nanocrystals. XPS spectra show evidence of unique interactions between TiO2 and basic sites in these samples. UV diffuse reflectance shows that PDVB-VI-TiO2-x and PDVB-Py-TiO2-x exhibit a unique response to visible light. Catalytic tests show that the PDVB-VI-TiO2-x and PDVB-Py-TiO2-x were active in catalyzing the degradation of PNP and RhB organic pollutants under visible light irradiation. The enhanced activities of the PDVB-VI-TiO2-x and PDVB-Py-TiO2-x were ascribed to synergistic effects between abundant nanopores and the unique optical adsorption of visible light in the samples.

20.
Appl Microbiol Biotechnol ; 99(5): 2105-17, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25480510

RESUMEN

1,3-propanediol (1,3-PD) was produced with a robust fermentation process using waste glycerol feedstock from biodiesel production and a soil-based bacterial inoculum. An iterative inoculation method was developed to achieve independence from soil and selectively breed bacterial populations capable of glycerol metabolism to 1,3-PD. The inoculum showed high resistance to impurities in the feedstock. 1,3-PD selectivity and yield in batch fermentations was optimized by appropriate nutrient compositions and pH control. The batch yield of 1,3-PD was maximized to ~0.7 mol/mol for industrial glycerol which was higher than that for pure glycerin. 16S rDNA sequencing results show a systematic selective enrichment of 1,3-PD producing bacteria with iterative inoculation and subsequent process control. A statistical design of experiments was carried out on industrial glycerol batches to optimize conditions, which were used to run two continuous flow stirred-tank reactor (CSTR) experiments over a period of >500 h each. A detailed analysis of steady states at three dilution rates is presented. Enhanced specific 1,3-PD productivity was observed with faster dilution rates due to lower levels of solvent degeneration. 1,3-PD productivity, specific productivity, and yield of 1.1 g/l hr, 1.5 g/g hr, and 0.6 mol/mol of glycerol were obtained at a dilution rate of 0.1 h(-1)which is bettered only by pure strains in pure glycerin feeds.


Asunto(s)
Glicerol/metabolismo , Consorcios Microbianos , Glicoles de Propileno/metabolismo , Microbiología del Suelo , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , Medios de Cultivo/química , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Fermentación , Concentración de Iones de Hidrógeno , Residuos Industriales , Datos de Secuencia Molecular , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
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