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1.
Nanoscale ; 11(43): 20766-20776, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31651003

RESUMO

A major impediment in the clinical translation of stem cell therapy has been the inability to efficiently and reproducibly direct differentiation of a large population of stem cells. Thus, we aimed to engineer a substrate for culturing stem cells to efficiently induce cardiomyogenic lineage commitment. In this work, we present a nanopillar array on the surface of titanium that was prepared by mask-less reactive ion etching. Scanning electron and atomic force microscopy revealed that the surface was covered by vertically aligned nanopillars each of ≈1 µm with a diameter of ≈80 nm. The nanopillars supported the attachment and proliferation of human mesenchymal stem cells (hMSCs). Cardiomyogenic lineage commitment of the stem cells was more enhanced on the nanopillars than on the smooth surface. When co-cultured with neonatal rat cardiomyocytes, the cyclic pattern of calcium transport observed distinctly in cells differentiated on the arrays compared to the cells cultured on the smooth surface was the functional validation of differentiation. The use of small molecule inhibitors revealed that integrins namely, α2ß1 and αvß3, are essential for cardiomyogenesis on the nanostructured surface, which is further mediated by FAK, Erk and Akt cell signaling pathways. This study demonstrates that the nanopillar array efficiently promotes the cardiomyogenic lineage commitment of stem cells via integrin-mediated signaling and can potentially serve as a platform for the ex vivo differentiation of stem cells toward cell therapy in cardiac tissue repair and regeneration.


Assuntos
Diferenciação Celular , Nanoestruturas/química , Titânio/química , Animais , Cálcio/metabolismo , Linhagem da Célula , Proliferação de Células , Técnicas de Cocultura , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteína Homeobox Nkx-2.5/metabolismo , Humanos , Integrina alfa2beta1/antagonistas & inibidores , Integrina alfa2beta1/metabolismo , Integrina alfaVbeta3/antagonistas & inibidores , Integrina alfaVbeta3/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Microscopia Confocal , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Propriedades de Superfície
2.
ACS Appl Mater Interfaces ; 11(7): 7566-7575, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30681825

RESUMO

Unique two-dimensional water channels formed by stacked graphene oxide (GO) sheets that are "nonleachable" and nonswellable can show great potential for water remediation. The interlayer spacing controls the solute or ion sieving and plays a crucial role in water transport in GO-based membranes. Herein, the sub-nano-channels adjacent to the sheets are altered by either ionic or covalent cross-linking using magnesium hydroxide (Mg(OH)2) and graphene oxide quantum dots (GQDs) (named GOM and G-GQD), respectively. In aqueous solution, these cross-linkers prevent the GO sheets from swelling and precisely control the interlayer spacing required for water permeation. In addition, these narrowed GO sheets facilitate significant improvement in salt rejection of a divalent ion by forward osmosis and selective dye rejection and are resistive toward biofouling and bacterial growth. The cross-linked GO membranes are robust enough to withstand strong cross-flow velocity and aided in unimpeded water transport through the nanochannels. Among the membranes, the G-GQD membranes (G-GQD) show better antifouling characteristics, dye separation performance over 95-97% for various dyes, divalent ion rejection by 97%, and no cytotoxicity against HaCaT cells as compared with other GO membranes. Our findings on interlocking the domains of nanoslits of the GO structure by small ecofriendly molecules portray these materials as potential candidates for water separation applications.


Assuntos
Grafite/química , Membranas Artificiais , Osmose , Pontos Quânticos/química , Purificação da Água/métodos , Linhagem Celular , Grafite/farmacologia , Humanos , Teste de Materiais , Porosidade
3.
ACS Appl Mater Interfaces ; 10(26): 21816-21824, 2018 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-29877694

RESUMO

Phytochemicals constitute a promising class of therapeutics for the treatment of various diseases, but their delivery poses significant challenges. In this work, a nanoscale polyactive emulsion was designed for smart, cell-responsive delivery of a curcumin prodrug (curcumin dicarboxylate, CDA) that was chemically conjugated to enzymatically labile oligo-peptides with polycaprolactone (PCL) as the carrier. Matrix metalloproteinase (MMP)-sensitive (PLGLYAL) or nonsensitive (GPYYPLG) peptides were used as spacers for conjugating CDA and PCL. This CDA nanoemulsion incorporating the MMP-sensitive sequence exhibited markedly higher anti-cancer activity, cell internalization, and generation of reactive oxygen species in cancer cells in vitro than the control with the nonsensitive oligopeptide. Moreover, the nanopolyactives induced minimal cytotoxicity in noncancerous cell line. This work presents a unique strategy to engineer smart nano-polyactives for efficient and targeted delivery of phytochemicals.


Assuntos
Compostos Fitoquímicos/química , Antineoplásicos , Curcumina , Portadores de Fármacos , Micelas , Nanopartículas , Polímeros
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