RESUMEN
PURPOSE: To develop a biomaterial composite for promoting proliferation and migration of neural stem cells (NSCs), as well as angiogenesis on the materials, to rescue central nervous system (CNS) injuries. METHODS: A delivery system was constructed based on cross-linked hyaluronic acid (HA) hydrogels, containing embedded BDNF and VEGF-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres for controlled delivery and support for NSCs in the CNS. The surface morphologies were evaluated by SEM and AFM, mechanical property was investigated by rheological tests, and release kinetics were performed by ELISA. Bioactivity of released BDNF and VEGF was assessed by neuron and endothelial cell culture, respectively. Compatibility with NSCs was studied by immunofluorescent staining. RESULTS: Release kinetics showed the delivery of BDNF and VEGF from PLGA microspheres and HA hydrogel composite were sustainable and stable, releasing ~20-30% within 150 h. The bioactivities preserved well to promote survival and growth of the cells. Evaluation of structure and mechanical properties showed the hydrogel composite possessed an elastic scaffold structure. Biocompatibility assay showed NSCs adhered and proliferated well on the hydrogel. CONCLUSIONS: Our created HA hydrogel/PLGA microsphere systems have a good potential for controlled delivery of varied biofactors and supporting NSCs for brain repair and implantation.
Asunto(s)
Ácido Hialurónico/química , Hidrogeles/química , Ácido Láctico/química , Microesferas , Células-Madre Neurales/citología , Ácido Poliglicólico/química , Andamios del Tejido , Animales , Materiales Biocompatibles/química , Factor Neurotrófico Derivado del Encéfalo/administración & dosificación , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Preparaciones de Acción Retardada , Células Endoteliales/efectos de los fármacos , Humanos , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/trasplante , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ratas , Ratas Sprague-Dawley , Factor A de Crecimiento Endotelial Vascular/administración & dosificaciónRESUMEN
The using of layer-by-layer assembly polyelectrolyte (PE) films has been suggested as a new versatile technique for surface modification aimed at tissue engineering and cell-based chips. In this study, we investigated the surface morphology of the hyaluronic acid (HA)-based PE films deposited on the amino-functionalized glass slides using atomic force microscopy. These thin films (bilayer number <9) were measured to have nanoscale roughness ranging from 10 to 100 nm. Then the primary hippocampal and cortical neural cells were cultured on the PE films, respectively. After 5 days of culturing, the cytocompatibility to neural cells was evaluated by cellular morphology, neurite outgrowth, and microtubule-associated protein 2 expressions. From the present results, the HA-based PE films were found to be able to support neural cell adhesion and neurite development, especially for the polycation-ending films. It is suggested these HA-based multilayer PE films or similar build-ups could thus be used in the future as a way to modify surfaces for nerve scaffolds and neuron-based chips.