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1.
Int J Biomater ; 2022: 3255039, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35154326

RESUMEN

In the last decades, cell-based approaches for bone tissue engineering (BTE) have relied on using models that cannot replicate the complexity of the bone microenvironment. There is an ongoing amount of research on scaffold development responding to the need for feasible materials that can mimic the bone extracellular matrix (ECM) and aid bone tissue regeneration (BTR). In this work, a porous cellulose acetate (CA) fiber mat was developed using the electrospinning technique and the mats were chemically modified to bioactivate their surface and promote osteoconduction and osteoinduction. The mats were characterized using FTIR and SEM/EDS to validate the chemical modifications and assess their structural integrity. By coupling adhesive peptides KRSR, RGD, and growth factor BMP-2, the fiber mats were bioactivated, and their induced biological responses were evaluated by employing immunocytochemical (ICC) techniques to study the adhesion, proliferation, and differentiation of premature osteoblast cells (hFOB 1.19). The biological assessment revealed that at short culturing periods of 48 hours and 7 days, the presence of the peptides was significant for proliferation and adhesion, whereas at longer culture times of 14 days, it had no significant effect on differentiation and maturation of the osteogenic progenitor cells. Based on the obtained results, it is thus concluded that the CA porous fiber mats provide a promising surface morphology that is both biocompatible and can be rendered bioactive upon the addition of osteogenic peptides to favor osteoconduction leading to new tissue formation.

2.
Science ; 375(6576): 91-96, 2022 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-34990237

RESUMEN

Fibrosis affects millions of people with cardiac disease. We developed a therapeutic approach to generate transient antifibrotic chimeric antigen receptor (CAR) T cells in vivo by delivering modified messenger RNA (mRNA) in T cell­targeted lipid nanoparticles (LNPs). The efficacy of these in vivo­reprogrammed CAR T cells was evaluated by injecting CD5-targeted LNPs into a mouse model of heart failure. Efficient delivery of modified mRNA encoding the CAR to T lymphocytes was observed, which produced transient, effective CAR T cells in vivo. Antifibrotic CAR T cells exhibited trogocytosis and retained the target antigen as they accumulated in the spleen. Treatment with modified mRNA-targeted LNPs reduced fibrosis and restored cardiac function after injury. In vivo generation of CAR T cells may hold promise as a therapeutic platform to treat various diseases.


Asunto(s)
Ingeniería Celular , Endopeptidasas/inmunología , Cardiopatías/terapia , Inmunoterapia Adoptiva , Liposomas , Proteínas de la Membrana/inmunología , Nanopartículas , Receptores Quiméricos de Antígenos/inmunología , Linfocitos T/inmunología , Traslado Adoptivo , Animales , Antígenos CD5/inmunología , Endopeptidasas/metabolismo , Fibroblastos/inmunología , Fibroblastos/patología , Fibrosis/terapia , Células HEK293 , Cardiopatías/patología , Insuficiencia Cardíaca/terapia , Humanos , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Miocardio/patología , ARN Mensajero/genética , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/metabolismo , Bazo/inmunología , Trogocitosis
3.
ACS Omega ; 7(3): 2774-2785, 2022 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-35097274

RESUMEN

Polyphenols are natural compounds with strong antioxidant properties synthesized by plants and widely distributed in plant tissues. They compose a broad class of compounds that are commonly employed for multiple applications such as food, pharmaceutical, adhesives, biomedical, agricultural, and industrial purposes. Runoffs from these sources result in the introduction of polyphenols into aquatic environments where they further transform into highly toxic pollutants that can negatively affect aquatic ecosystems and humans. Therefore, the development of extraction and remediation methods for such compounds must be addressed. This study describes the identification and operation of a method to recover polyphenolic compounds from water environments by utilizing membrane-based separation. Composite membranes derived from electrospun cellulose acetate (CA) fibers and diblock copolymer (DiBCP) PEO-b-P4VP were prepared to evaluate the adsorption of polyphenolic compounds from aqueous environments. The highly porous CA fibers were developed using the electrospinning technique, and the fabricated DiBCP/CA membranes were characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared (FT-IR) spectroscopy, and tensile testing. Finally, the ability of the composite membranes to adsorb the soluble polyphenolic compounds catechol (CAT) and gallic acid (GA), from a wetland environment, was studied via batch adsorption experiments and by solid-phase extraction (SPE). Results revealed a successful recovery of both polyphenols, at concentrations within the parts per million (ppm) range, from the aqueous media. This suggests a novel approach to recover these compounds to prevent their transformation into toxic pollutants upon entrance to water environments.

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