Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/172754
COMPARTIR / EXPORTAR:
logo share SHARE logo core CORE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE

Invitar a revisión por pares abierta
Título

Pro-angiogenic near infrared-responsive hydrogels for deliberate transgene expression

AutorMartín-Saavedra, Francisco; Escudero-Duch, Clara; Prieto, Martín; Sánchez-Casanova, S.; López García, Daniel CSIC ORCID ; Arruebo, Manuel CSIC ORCID; Voellmy, Richard; Santamaría, J.; Ricote, J. CSIC ORCID; Vilaboa, Nuria
Palabras claveAngiogenesis
Near-infrared
Copper
Scaffold
Hydrogel
Gene therapy
Fecha de publicación2018
EditorElsevier
CitaciónActa Biomaterialia 78: 123-136 (2018)
ResumenCuS nanoparticles (CuSNP) are degradable, readily prepared, inexpensive to produce and efficiently cleared from the body. In this work, we explored the feasibility of CuSNP to function as degradable near infrared (NIR) nanotransducers within fibrin-based cellular scaffolds. To prepare NIR-responsive CuSNP hydrogels, fibrinogen was dissolved in cell culture medium and supplemented with aqueous dispersions of CuSNP. Fibrinogen polymerization was catalyzed by the addition of thrombin. In some experiments, HUVEC, C3H/10T1/2 or C3H/10T1/2-fLuc cells, that harbor a heat-activated and rapamycin-dependent gene switch for regulating the expression of firefly luciferase transgene, were incorporated to the sol phase of the hydrogel. For in vivo experiments, hydrogels were injected subcutaneously in the back of adult C3H/HeN mice. Upon NIR irradiation, CuSNP hydrogels allowed heat-inducible and rapamycin-dependent transgene expression in cells contained therein, in vitro and in vivo. C3H/10T1/2 cells cultured in CuSNP hydrogels increased metabolic activity, survival rate and fibrinolytic activity, which correlated with changes at the transcriptome level. Media conditioned by CuSNP hydrogels increased viability of HUVEC which formed pseudocapillary structures and remodeled protein matrix when entrapped within these hydrogels. After long-term implantation, the skin patches that covered the CuSNP hydrogels showed increased capillary density which was not detected in mice implanted with matrices lacking CuSNP. In summary, NIR-responsive scaffolds harboring CuSNP offer compelling features in the tissue engineering field, as degradable implants with enhanced integration capacity in host tissues that can provide remote controlled deployment of therapeutic gene products. Statement of Significance: Hydrogels composed of fibrin embedding copper sulfide nanoparticles (CuSNP) efficiently convert incident near infrared (NIR) energy into heat and can function as cellular scaffolding. NIR laser irradiation of CuSNP hydrogels can be employed to remotely induce spatiotemporal patterns of transgene expression in genetically engineered multipotent stem cells. CuSNP incorporation in hydrogel architecture accelerates the cell-mediated degradation of the fibrin matrix and induces pro-angiogenic responses that may facilitate the integration of these NIR-responsive scaffolds in host tissues. CuSNP hydrogels that harbor cells capable of controlled expression of therapeutic gene products may be well suited for tissue engineering as they are biodegradable, enhance implant vascularization and can be used to deploy growth factors in a desired spatiotemporal fashion.
Versión del editorhttp://dx.doi.org/10.1016/j.actbio.2018.08.006
URIhttp://hdl.handle.net/10261/172754
DOI10.1016/j.actbio.2018.08.006
Identificadoresdoi: 10.1016/j.actbio.2018.08.006
issn: 1742-7061
e-issn: 1878-7568
Aparece en las colecciones: (ICTP) Artículos




Ficheros en este ítem:
Fichero Descripción Tamaño Formato
accesoRestringido.pdf15,38 kBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo

CORE Recommender

SCOPUSTM   
Citations

11
checked on 19-mar-2024

WEB OF SCIENCETM
Citations

11
checked on 20-feb-2024

Page view(s)

253
checked on 19-abr-2024

Download(s)

119
checked on 19-abr-2024

Google ScholarTM

Check

Altmetric

Altmetric


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.