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1.
Pharm Res ; 31(12): 3335-47, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24852896

RESUMEN

PURPOSE: For building functional vasculature, controlled delivery of fibroblast growth factor-9 (FGF9) from electrospun fibers is an appealing strategy to overcome challenges associated with its short half-life. FGF9 sustained delivery could potentially drive muscularization of angiogenic sprouts and help regenerate stable functional neovasculature in ischemic vascular disease patients. METHODS: Electrospinning parameters of FGF9-loaded poly(ester amide) (PEA) fibers have been optimized, using blend and emulsion electrospinning techniques. In vitro PEA matrix degradation, biocompatibility, FGF9 release kinetics, and bioactivity of the released FGF9 were evaluated. qPCR was employed to evaluate platelet-derived growth factor receptor-ß (PDGFRß) gene expression in NIH-3T3 fibroblasts, 10T1/2 cells, and human coronary artery smooth muscle cells cultured on PEA fibers at different FGF9 concentrations. RESULTS: Loaded PEA fibers exhibited controlled release of FGF9 over 28 days with limited burst effect while preserving FGF9 bioactivity. FGF9-loaded and unloaded electrospun fibers were found to support the proliferation of fibroblasts for five days even in serum-depleted conditions. Cells cultured on FGF9-supplemented PEA mats resulted in upregulation of PDGFRß in concentration and cell type-dependent manner. CONCLUSION: This study supports the premise of controlled delivery of FGF9 from PEA electrospun fibers for potential therapeutic angiogenesis applications.


Asunto(s)
Factor 9 de Crecimiento de Fibroblastos/administración & dosificación , Factor 9 de Crecimiento de Fibroblastos/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Amidas , Animales , Supervivencia Celular/efectos de los fármacos , Vasos Coronarios/citología , Vasos Coronarios/efectos de los fármacos , Preparaciones de Acción Retardada , Ratones , Microscopía Confocal , Músculo Liso Vascular/efectos de los fármacos , Células 3T3 NIH , Poliésteres
2.
Polymers (Basel) ; 16(6)2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38543353

RESUMEN

Calcium-containing organic-inorganic nanocomposites play an essential role in developing bioactive bone biomaterials. Ideally, bone substitute materials should mimic the organic-inorganic composition of bone. In this study, the roles of calcium chloride (CaCl2) and calcium ethoxide (Ca(OEt)2) were evaluated for the development of sol-gel-derived organic-inorganic biomaterials composed of gelatin, bioactive glass (BG) and multiwall carbon nanotubes (MWCNTs) to create nanocomposites that mimic the elemental composition of bone. Nanocomposites composed of either CaCl2 or Ca(OEt)2 were chemically different but presented uniform elemental distribution. The role of calcium sources in the matrix of the nanocomposites played a major role in the swelling and degradation properties of biomaterials as a function of time, as well as the resulting porous properties of the nanocomposites. Regardless of the calcium source type, biomineralization in simulated body fluid and favorable cell attachment were promoted on the nanocomposites. 10T1/2 cell viability studies using standard media (DMEM with 5% FBS) and conditioned media showed that Ca(OEt)2-based nanocomposites seemed more favorable biomaterials. Collectively, our study demonstrated that CaCl2 and Ca(OEt)2 could be used to prepare sol-gel-derived gelatin-BG-MWCNT nanocomposites, which have the potential to function as bone biomaterials.

3.
Biomimetics (Basel) ; 9(6)2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38921218

RESUMEN

The ability of bone biomaterials to promote osteogenic differentiation is crucial for the repair and regeneration of osseous tissue. The development of a temporary bone substitute is of major importance in enhancing the growth and differentiation of human-derived stem cells into an osteogenic lineage. In this study, nanocomposite hydrogels composed of gelatin methacryloyl (GelMA), bioactive glass (BG), and multiwall carbon nanotubes (MWCNT) were developed to create a bone biomaterial that mimics the structural and electrically conductive nature of bone that can promote the differentiation of human-derived stem cells. GelMA-BG-MWCNT nanocomposite hydrogels supported mesenchymal stem cells derived from human induced pluripotent stem cells, hereinafter named iMSCs. Cell adhesion was improved upon coating nanocomposite hydrogels with fibronectin and was further enhanced when seeding pre-differentiated iMSCs. Osteogenic differentiation and mature mineralization were promoted in GelMA-BG-MWCNT nanocomposite hydrogels and were most evidently observed in the 70-30-2 hydrogels, which could be due to the stiff topography characteristic from the addition of MWCNT. Overall, the results of this study showed that GelMA-BG-MWCNT nanocomposite hydrogels coated with fibronectin possessed a favorable environment in which pre-differentiated iMSCs could better attach, proliferate, and further mature into an osteogenic lineage, which was crucial for the repair and regeneration of bone.

4.
Adv Healthc Mater ; : e2401218, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39036851

RESUMEN

Native tissues, comprising multiple cell types and extracellular matrix components, are inherently composites. Mimicking the intricate structure, functionality, and dynamic properties of native composite tissues represents a significant frontier in biomaterials science and tissue engineering research. Biomimetic composite biomaterials combine the benefits of different components, such as polymers, ceramics, metals, and biomolecules, to create tissue-template materials that closely simulate the structure and functionality of native tissues. While the design of composite biomaterials and their in vitro testing are frequently reviewed, there is a considerable gap in whole animal studies that provides insight into the progress toward clinical translation. Herein, we provide an insightful critical review of advanced composite biomaterials applicable in several tissues. The incorporation of bioactive cues and signaling molecules into composite biomaterials to mimic the native microenvironment is discussed. Strategies for the spatiotemporal release of growth factors, cytokines, and extracellular matrix proteins are elucidated, highlighting their role in guiding cellular behavior, promoting tissue regeneration, and modulating immune responses. Advanced composite biomaterials design challenges, such as achieving optimal mechanical properties, improving long-term stability, and integrating multifunctionality into composite biomaterials and future directions, are discussed. We believe that this manuscript provides the reader with a timely perspective on composite biomaterials.

5.
Environ Sci Pollut Res Int ; 31(6): 8736-8750, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38180650

RESUMEN

A single-step dye removal strategy from wastewater is inadequate for concentrations above 100 mg/L. In order to address this limitation, the adsorption of high dye concentrations followed by phytoremediation is a potential approach for the treatment of dye-contaminated wastewater. This combined method utilizes physical adsorption and biological processes to remove dyes from wastewater. Herein, we investigated a pilot-scale multi-step cascaded process where batch adsorption and fixed-bed column adsorption were combined with phytoremediation to remove cellulose-reactive blue dye at 200 to 500 mg/L concentrations. The batch adsorption utilized low-cost water hyacinth root powder (WHRP) bioadsorbent having 670 m2/g surface area, whereas the fixed-bed column adsorption used sand having a surface area of 75 m2/g. The phytoremediation process utilized water hyacinth plants in a series of ponds. The effluent from one unit is fed to the next until the dye is removed to more than 98% for all concentrations considered in this study. Pilot-scale experimental data fitting to adsorption isotherms and kinetics were performed to gain insight into the pilot-scale adsorption mechanism. The fixed-bed sand column adsorption was conducted at different inlet dye concentrations, flow rates, and bed heights. The breakthrough curves were fit to the Thomas, Yoon-Nelson, and Bohart-Adams models. The effluent from the fixed-bed column was transferred to phytoremediation ponds, where complete dye removal was achieved. Overall, data collectively presented in this study demonstrated that the combined adsorption and phytoremediation approach offers a potential solution for the remediation of high dye concentration in wastewater, providing an effective and sustainable treatment option.


Asunto(s)
Contaminantes Químicos del Agua , Purificación del Agua , Aguas Residuales , Celulosa , Adsorción , Colorantes , Biodegradación Ambiental , Arena , Purificación del Agua/métodos , Contaminantes Químicos del Agua/análisis , Cinética
6.
Adv Healthc Mater ; 13(17): e2304523, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38345186

RESUMEN

Achieving hemostasis in penetrating and irregular wounds is challenging because the hemostasis factor cannot arrive at the bleeding site, and substantial bleeding will wash away the blood clot. Since the inherently gradual nature of blood clot formation takes time, a physical barrier is needed before blood clot formation. Herein, an ultra-light and shape memory hemostatic aerogel consisting of oxidized bacterial cellulose (OBC) and platelet extracellular vesicles (pVEs) is reported. The OBC-pVEs aerogel provides a physical barrier for the bleeding site by self-expansion, absorbing the liquid from blood to concentrate platelets and clotting factors and accelerating the clot formation by activating platelets and transforming fibrinogen into fibrin. In the rat liver and tail injury models, the blood loss decreases by 73% and 59%, and the bleeding times are reduced by 55% and 62%, respectively. OBC-pVEs aerogel has also been shown to accelerate wound healing. In conclusion, this work introduces an effective tool for treating deep, non-compressible, and irregular wounds and offers valuable strategies for trauma bleeding and wound treatment.


Asunto(s)
Plaquetas , Geles , Hemostasis , Cicatrización de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Hemostasis/efectos de los fármacos , Ratas , Plaquetas/metabolismo , Geles/química , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/química , Masculino , Ratas Sprague-Dawley , Celulosa/química , Coagulación Sanguínea/efectos de los fármacos , Celulosa Oxidada/química , Celulosa Oxidada/farmacología , Hemorragia , Hemostáticos/farmacología , Hemostáticos/química , Humanos
7.
Adv Sci (Weinh) ; 11(21): e2306917, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38439601

RESUMEN

Nature presents the most beautiful patterns through evolving. Here, a layered porous pattern in golden ratio (0.618) is reported from a type of mushroom -Dictyophora Rubrovalvata stipe (DRS). The hierarchical structure shows a mathematical correlation with the golden ratio. This unique structure leads to superior mechanical properties. The gradient porous structure from outside to innermost endows it with asymmetrical hydrophilicity. A mathematical model is then developed to predict and apply to 3D printed structures. The mushroom is then explored to repair gastric perforation because the stomach is a continuous peristaltic organ, and the perforated site is subject to repeated mechanical movements and pressure changes. At present, endoscopic clipping is ineffective in treating ulcerative perforation with fragile surrounding tissues. Although endoscopic implant occlusion provides a new direction for the treatment of gastric ulcers, but the metal or plastic occluder needs to be removed, requiring a second intervention. Decellularized DRS (DDRS) is found with asymmetric water absorption rate, super-compressive elasticity, shape memory, and biocompatibility, making it a suitable occluder for the gastric perforation. The efficacy in blocking gastric perforation and promoting healing is confirmed by endoscopic observation and tissue analysis during a 2-month study.


Asunto(s)
Agaricales , Animales , Estómago/cirugía , Estómago/lesiones , Hemostáticos/uso terapéutico , Cicatrización de Heridas/fisiología , Impresión Tridimensional , Modelos Teóricos
8.
Adv Mater ; 36(40): e2405290, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39011814

RESUMEN

In an emergency, nonvariceal upper gastrointestinal bleeding (NVUGIB), endoscopic hemostasis is considered the gold standard intervention. However, current endoscopic hemostasis is very challenging to manage bleeding in large-diameter or deep lesions highly prone to rebleeding risk. Herein, a novel hemostatic peptide hydrogel (HPH) is reported, consisting of a self-assembly peptide sequence CFLIVIGSIIVPGDGVPGDG (PFV) and gelatin methacryloyl (GelMA), which can be triggered by blue laser endoscopy (BLE) for nonvariceal upper gastrointestinal bleeding treatment without recurring bleeding concerns. Upon contact with GelMA solution, PFV immediately fibrillates into ß-sheet nanofiber and solvent-induced self-assembly to form HPH gel. HPH nanofiber networks induced ultrafast coagulation by enveloping blood cells and activating platelets and coagulation factors even to the blood with coagulopathy. Besides its remarkable hemostatic performance in artery and liver injury models, HPH achieves instant bleeding management in porcine NVUGIB models within 60 s by preventing the rebleeding risk. This work demonstrates an extraordinary hemostatic agent for NVUGIB intervention by BLE for the first time, broadening potential application scenarios, including patients with coagulopathy and promising clinical prospects.


Asunto(s)
Hemorragia Gastrointestinal , Hemostáticos , Hidrogeles , Péptidos , Hidrogeles/química , Animales , Hemorragia Gastrointestinal/terapia , Péptidos/química , Hemostáticos/química , Hemostáticos/farmacología , Porcinos , Rayos Láser , Humanos , Gelatina/química , Nanofibras/química
9.
Nat Commun ; 15(1): 4133, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755124

RESUMEN

Conductive cardiac patches can rebuild the electroactive microenvironment for the infarcted myocardium but their repair effects benefit by carried seed cells or drugs. The key to success is the effective integration of electrical stimulation with the microenvironment created by conductive cardiac patches. Besides, due to the concerns in a high re-admission ratio of heart patients, a remote medicine device will underpin the successful repair. Herein, we report a miniature self-powered biomimetic trinity triboelectric nanogenerator with a unique double-spacer structure that unifies energy harvesting, therapeutics, and diagnosis in one cardiac patch. Trinity triboelectric nanogenerator conductive cardiac patches improve the electroactivity of the infarcted heart and can also wirelessly monitor electrocardiosignal to a mobile device for diagnosis. RNA sequencing analysis from rat hearts reveals that this trinity cardiac patches mainly regulates cardiac muscle contraction-, energy metabolism-, and vascular regulation-related mRNA expressions in vivo. The research is spawning a device that truly integrates an electrical stimulation of a functional heart patch and self-powered e-care remote diagnostic sensor.


Asunto(s)
Infarto del Miocardio , Animales , Infarto del Miocardio/terapia , Infarto del Miocardio/fisiopatología , Ratas , Miocardio/metabolismo , Miocardio/patología , Masculino , Ratas Sprague-Dawley , Estimulación Eléctrica , Humanos , Contracción Miocárdica
10.
J Vasc Res ; 50(1): 35-51, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23154615

RESUMEN

Therapeutic angiogenesis is a new revascularization strategy involving the administration of growth factors to induce new vessel formation. The biology and delivery of angiogenic growth factors involved in vessel formation have been extensively studied but success in translating the angiogenic capacity of growth factors into benefits for vascular disease patients is still limited. This could be attributed to issues related to patient selection, growth factor delivery methods or lack of vessel maturation. Comprehensive understanding of the cellular and molecular cross-talk during the different stages of vascular development is needed for the design of efficient therapeutic strategies. The presentation of angiogenic factors either in series or in parallel using a strategy that mimics physiological events, such as concentration and spatio-temporal profiles, is an immediate requirement for functional blood vessel formation. This review provides an overview of the recent delivery strategies of angiogenic factors and discusses targeting neovascular maturation as a promising approach to induce stable and functional vessels for therapeutic angiogenesis.


Asunto(s)
Inductores de la Angiogénesis/administración & dosificación , Proteínas Angiogénicas/administración & dosificación , Proteínas Angiogénicas/genética , Portadores de Fármacos , Terapia Genética , Isquemia Miocárdica/terapia , Neovascularización Fisiológica , Proteínas Angiogénicas/biosíntesis , Animales , Preparaciones de Acción Retardada , Humanos , Terapia Molecular Dirigida , Isquemia Miocárdica/genética , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatología , Neovascularización Fisiológica/efectos de los fármacos , Neovascularización Fisiológica/genética , Regeneración
11.
Proc Inst Mech Eng H ; 227(4): 402-20, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23637216

RESUMEN

This review focuses on the modeling of articular cartilage (at the tissue level), chondrocyte mechanobiology (at the cell level) and a combination of both in a multiscale computation scheme. The primary objective is to evaluate the advantages and disadvantages of conventional models implemented to study the mechanics of the articular cartilage tissue and chondrocytes. From monophasic material models as the simplest form to more complicated multiscale theories, these approaches have been frequently used to model articular cartilage and have contributed significantly to modeling joint mechanics, addressing and resolving numerous issues regarding cartilage mechanics and function. It should be noted that attentiveness is important when using different modeling approaches, as the choice of the model limits the applications available. In this review, we discuss the conventional models applicable to some of the mechanical aspects of articular cartilage such as lubrication, swelling pressure and chondrocyte mechanics and address some of the issues associated with the current modeling approaches. We then suggest future pathways for a more realistic modeling strategy as applied for the simulation of the mechanics of the cartilage tissue using multiscale and parallelized finite element method.


Asunto(s)
Cartílago Articular/patología , Modelos Biológicos , Animales , Materiales Biocompatibles/química , Cartílago/patología , Cartílago Articular/citología , Condrocitos/citología , Condrocitos/patología , Sulfatos de Condroitina/química , Fuerza Compresiva , Simulación por Computador , Análisis de Elementos Finitos , Humanos , Sulfato de Queratano/química , Articulación de la Rodilla/patología , Modelos Estadísticos , Modelos Teóricos , Porosidad , Estrés Mecánico , Propiedades de Superficie
12.
Pharmaceutics ; 15(11)2023 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-38004526

RESUMEN

This study investigates the mechanical properties, degradation behavior, and biocompatibility of poly[(α-amino acid ester) phosphazene] electrospun fibers based on the ethyl ester of L-methionine (PαAPz-M), a material with potential applications in tissue engineering. We utilized atomic force microscopy (AFM) to evaluate the fiber mechanical characteristics and calculate its Young's modulus, revealing it to closely mimic the stiffness of a natural extracellular matrix (ECM). We also studied the degradation behavior of PαAPz-M scaffolds over 21 days, showing that they maintain the highly porous structure required for tissue engineering. Further evaluation of mesenchymal multipotent 10T1/2 cell and mesenchymal stem cell (MSC) behavior on the scaffolds demonstrated significant cell viability, proliferation, and successful MSC differentiation into smooth muscle cells. Expression of collagen and elastin by MSCs on the fiber mats highlighted potential ECM formation during scaffold degradation, confirming PαAPz-M as a promising material for vascular tissue engineering.

13.
Biomater Adv ; 154: 213616, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37708668

RESUMEN

Natural bone is a complex organic-inorganic composite tissue that possesses endogenous electrically conductive properties in response to mechanical forces. Mimicking these unique properties collectively in a single synthetic biomaterial has so far remained a formidable task. In this study, we report a synthesis strategy that comprised gelatin methacryloyl (GelMA), sol-gel derived tertiary bioactive glass (BG), and uniformly dispersed multiwall carbon nanotubes (MWCNTs) to create nanocomposite hydrogels that mimic the organic-inorganic composition of bone. Using this strategy, biomaterials that are electrically conductive and possess electro-mechanical properties similar to endogenous bone were prepared without affecting their biocompatibility. Nanocomposite hydrogel biomaterials were biodegradable and promoted biomineralization, and supported multipotent mesenchymal progenitor cell (10T1/2) cell interactions and differentiation into an osteogenic lineage. To the best of our knowledge, this work presents the first study to functionally characterize suitable electro-mechanical responses in nanocomposite hydrogels, a key process that occurs in the natural bone to drive its repair and regeneration. Overall, the results demonstrated GelMA-BG-MWCNT nanocomposite hydrogels have the potential to become promising bioactive biomaterials for use in bone repair and regeneration.


Asunto(s)
Materiales Biocompatibles , Nanotubos de Carbono , Materiales Biocompatibles/farmacología , Nanogeles , Hidrogeles/farmacología
14.
Gels ; 9(4)2023 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-37102946

RESUMEN

Tetrazolium salts provide an appealing candidate for 3D gel dosimeters as they exhibit a low intrinsic color, no signal diffusion and excellent chemical stability. However, a previously developed commercial product (the ClearView 3D Dosimeter) based on a tetrazolium salt dispersed within a gellan gum matrix presented a noticeable dose rate effect. The goal of this study was to find out whether ClearView could be reformulated in order to minimize the dose rate effect by optimizing of the tetrazolium salt and gellan gum concentrations and by the addition a thickening agent, ionic crosslinkers, and radical scavengers. To that goal, a multifactorial design of experiments (DOE) was conducted in small-volume samples (4-mL cuvettes). It showed that the dose rate could be effectively minimized without sacrificing the integrity, chemical stability, or dose sensitivity of the dosimeter. The results from the DOE were used to prepare candidate formulations for larger-scale testing in 1-L samples to allow for fine-tuning the dosimeter formulation and conducting more detailed studies. Finally, an optimized formulation was scaled-up to a clinically relevant volume of 2.7 L and tested against a simulated arc treatment delivery with three spherical targets (diameter 3.0 cm), requiring different doses and dose rates. The results showed excellent geometric and dosimetric registration, with a gamma passing rate (at 10% minimum dose threshold) of 99.3% for dose difference and distance to agreement criteria of 3%/2 mm, compared to 95.7% in the previous formulation. This difference may be of clinical importance, as the new formulation may allow the quality assurance of complex treatment plans, relying on a variety of doses and dose rates; thus, expanding the potential practical application of the dosimeter.

15.
ACS Nano ; 17(1): 111-126, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36343209

RESUMEN

Gastrointestinal tract perforation is a full-thickness injury that causes bleeding and fatal infection of the peritoneum. This condition worsens in an acidic gastric environment which interferes with the normal coagulation cascade. Current endoscopic clips to repair gastric perforations are ineffective, and metal or plastic occluders need secondary surgery to remove them. Herein, we report a self-expandable, endoscopy deliverable, adhesive hydrogel to block gastric perforation. We found the nanosilica coating significantly enhanced the adhesive strength even under a simulated strong acidic stomach environment. The developed device was disulfide cross-linked for the reducible degraded gel. By loading with vonoprazan fumarate (VF) and acidic fibroblast growth factor (AFGF), the hyperboloid-shaped device can have a sustained drug release to regulate intragastric pH and promote wound healing. The gel device can be compressed and then expanded like a mushroom when applied in an acute gastric perforation model in both rabbits and minipigs. By utilizing a stomach capsule robot for remotely monitoring the pH and by immunohistochemical analysis, we demonstrated that the compressible hyperboloid-shaped gel could stably block the perforation and promoted wound healing during the 28 days of observation. The real-time pH meter demonstrated that the gel could control intragastric pH above 4 for nearly 60 h to prevent bleeding.


Asunto(s)
Agaricales , Gastropatías , Animales , Porcinos , Conejos , Hidrogeles , Porcinos Enanos , Endoscopía , Estómago , Adhesivos/farmacología
16.
Acta Biomater ; 158: 583-598, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36586500

RESUMEN

Gold nanoparticles (AuNPs) are prospective tools for nano-based medicine that can directly target cellular biological processes to influence cell fate and function. Studies have revealed the essential role of AuNPs in metabolic remodeling for macrophage polarization. Nevertheless, as a hallmark of cancer cells, metabolic changes in tumor cells in response to AuNPs have not yet been reported. In the present study, polymer- and folate-conjugated AuNPs with satisfactory biocompatibility and tumor-targeting activity were synthesized to investigate their underlying roles in tumor metabolism. Tumor cells were significantly suppressed by AuNPs in vitro and in vivo, with little cytotoxicity in non-tumor cells. Subcellular localization showed that AuNPs localized in the mitochondria of tumor cells and impaired their structure and function, leading to excessive oxidative stress and mitochondrial apoptosis. Metabolic stress, with decreased glycolysis and insufficient nutrients, was also caused by AuNPs exposure in tumor cells. Mechanistically, the key enzymes (GLUT1 and HK2) for glycolysis modulation were remarkably reduced by AuNPs in a c-Myc-dependent manner. The present study demonstrated a new mechanism for AuNPs in the inhibition of tumor growth, that is, via directly targeting glycolysis and depriving energy. These findings provide new strategies for the design of nano-based medicines and anti-glycolytic therapeutics to inhibit the development of malignant tumors. STATEMENT OF SIGNIFICANCE: Gold nanoparticles (AuNPs) have acquired ever-increasing interest for applications in cancer treatment and diagnosis due to their high biosafety and facile surface modification. Recent studies have shown that AuNPs can work as active agents to directly target the cellular processes and harbor antitumor properties, while the underlying mechanisms remain largely unknown. From the present findings, the stabilized AuNPs showed direct inhibition effects on tumor growth by glycolysis inhibition and energy deprivation. These results provide new insights of AuNPs for tumor treatments, which will further contribute to the development of promising nano-based medicines and anti-glycolytic therapies.


Asunto(s)
Nanopartículas del Metal , Neoplasias , Humanos , Oro/farmacología , Oro/química , Nanopartículas del Metal/uso terapéutico , Nanopartículas del Metal/química , Neoplasias/tratamiento farmacológico , Apoptosis , Línea Celular Tumoral
17.
Am J Pathol ; 179(5): 2189-98, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21907695

RESUMEN

Efficient deposition of type I collagen is fundamental to healing after myocardial infarction. Whether there is also a role for cleavage of type I collagen in infarct healing is unknown. To test this, we undertook coronary artery occlusion in mice with a targeted mutation (Col1a1(r/r)) that yields collagenase-resistant type I collagen. Eleven days after infarction, Col1a1(r/r) mice had a lower mean arterial pressure and peak left ventricular systolic pressure, reduced ventricular systolic function, and worse diastolic function, compared with wild-type littermates. Infarcted Col1a1(r/r) mice also had greater 30-day mortality, larger left ventricular lumens, and thinner infarct walls. Interestingly, the collagen fibril content within infarcts of mutant mice was not increased. However, circular polarization microscopy revealed impaired collagen fibril organization and mechanical testing indicated a predisposition to scar microdisruption. Three-dimensional lattices of collagenase-resistant fibrils underwent cell-mediated contraction, but the fibrils did not organize into birefringent collagen bundles. In addition, time-lapse microscopy revealed that, although cells migrated smoothly on wild-type collagen fibrils, crawling and repositioning on collagenase-resistant collagen was impaired. We conclude that type I collagen cleavage is required for efficient healing of myocardial infarcts and is critical for both dynamic positioning of collagen-producing cells and hierarchical assembly of collagen fibrils. This seemingly paradoxical requirement for collagen cleavage in fibrotic repair should be considered when designing potential strategies to inhibit matrix degradation in cardiac disease.


Asunto(s)
Colágeno Tipo I/metabolismo , Colagenasas/fisiología , Fibroblastos/enzimología , Infarto del Miocardio/enzimología , Cicatrización de Heridas/fisiología , Animales , Movimiento Celular , Colágeno Tipo I/genética , Cadena alfa 1 del Colágeno Tipo I , Colagenasas/genética , Constricción , Vasos Coronarios , Fibroblastos/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Mutación/genética
18.
Pharmaceutics ; 14(11)2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36365125

RESUMEN

Albumin is a natural biomaterial that is abundantly available in blood and body fluids. It is clinically used as a plasma expander, thereby increasing the plasma thiol concentration due to its cysteine residues. Albumin is a regulator of intervascular oncotic pressure, serves as an anti-inflammatory modulator, and it has a buffering role due to its histidine imidazole residues. Because of its unique biological and physical properties, albumin has also emerged as a suitable biomaterial for coating implantable devices, for cell and drug delivery, and as a scaffold for tissue engineering and regenerative medicine. As a biomaterial, albumin can be used as surface-modifying film or processed either as cross-linked protein gels or as electrospun fibers. Herein we have discussed how albumin protein can be utilized in regenerative medicine as a hydrogel and as a fibrous mat for a diverse role in successfully delivering drugs, genes, and cells to targeted tissues and organs. The review of prior studies indicated that albumin is a tunable biomaterial from which different types of scaffolds with mechanical properties adjustable for various biomedical applications can be fabricated. Based on the progress made to date, we concluded that albumin-based device coatings, delivery of drugs, genes, and cells are promising strategies in regenerative and personalized medicine.

19.
Chemosphere ; 303(Pt 2): 135024, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35618062

RESUMEN

Cellulose-reactive anionic dyes are one of the dominant colorants used in textile finishing. Unfortunately, they also produce large quantities of wastewater that must be treated before discharge, demanding low-cost and sustainable adsorbents that can easily be implemented, especially for developing countries with thriving cotton-based textile sectors. In this study, a high specific surface area (670 m2/g) water hyacinth root powder (WHRP) bioadsorbent that is neither carbonized nor activated was prepared to remove cellulose-reactive anionic blue dye from an aqueous solution. The effect of adsorption pH (pH = 2-8), adsorbent dose (1 g/L-6 g/L), dye concentration (50 mg/L-500 mg/L), adsorbent particle size (50 µm-1000 µm), mixing speed (100 rpm -200 rpm), and adsorption temperatures (22 °C-60 °C) were systematically studied. It was found that the protonation of lignin polyphenols in WHRP at pH = 2 was responsible for the observed high (∼99%) adsorptive removal of reactive blue dye. The maximum equilibrium adsorption capacity was 128.8 mg/g when 1 g/L WHRP and 500 mg/L dye concentration were used. In addition, adsorption isotherms, kinetic models, and adsorption thermodynamics were investigated. Increasing adsorbent dose, decreasing adsorbent particle size, increasing mixing speed, and lowering temperature favored the adsorption of reactive dye to WHRP adsorbent. The batch adsorption data were best fitted with both Langmuir and Temkin models, especially at 22 °C, while the adsorption kinetic behavior was described best using pseudo-second-order kinetics. Adsorption of cellulose-reactive blue dye to WHRP was spontaneous as characterized by the negative Gibbs energy (-11 kJ/mol to -24 kJ/mol) and exothermic with negative enthalpy (-13 kJ/mol to -23 kJ/mol). The overall adsorption process was controlled by more than one mechanism since the intraparticle diffusion was not the only rate-limiting step under our experimental conditions. Taken together, the abundantly available and sustainable WHRP is an efficient adsorbent that could be scaled up for treating cellulose-reactive dye-contaminated water.


Asunto(s)
Colorantes , Contaminantes Químicos del Agua , Adsorción , Aniones , Celulosa/química , Colorantes/química , Concentración de Iones de Hidrógeno , Cinética , Termodinámica , Contaminantes Químicos del Agua/química
20.
Polymers (Basel) ; 14(8)2022 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-35458303

RESUMEN

Mesenchymal stem cells, derived from human-induced pluripotent stem cells (iPSC), are valuable for generating smooth muscle cells (SMCs) for vascular tissue engineering applications. In this study, we synthesized biodegradable α-amino acid-substituted poly(organophosphazene) polymers and electrospun nano-fibrous scaffolds (~200 nm diameter) to evaluate their suitability as a matrix for differentiation of iPSC-derived mesenchymal stem cells (iMSC) into mature contractile SMCs. Both the polymer synthesis approach and the electrospinning parameters were optimized. Three types of cells, namely iMSC, bone marrow derived mesenchymal stem cells (BM-MSC), and primary human coronary artery SMC, attached and spread on the materials. Although L-ascorbic acid (AA) and transforming growth factor-beta 1 (TGF-ß1) were able to differentiate iMSC along the smooth muscle lineage, we showed that the electrospun fibrous mats provided material cues for the enhanced differentiation of iMSCs. Differentiation of iMSC to SMC was characterized by increased transcriptional levels of early to late-stage smooth muscle marker proteins on electrospun fibrous mats. Our findings provide a feasible strategy for engineering functional vascular tissues.

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