Reguera-Nuñez, ElaineRoca, CarlotaHardy, EugenioFuente, María de laCsaba, Noemi StefaniaGarcía-Fuentes, Marcos2014-02-122017-08-292014-01-07Reguera-Nuñez et al. Biomaterials 35, pp. 2859-2867 (2014)0142-9612http://hdl.handle.net/10347/9865Designing therapeutic devices capable of manipulating glioblastoma initiating cells (GICs) is critical to stop tumor recurrence and its associated mortality. Previous studies have indicated that bone morphogenetic protein-7 (BMP-7) acts as an endogenous suppressor of GICs, and thus, it could become a treatment for this cancer. In this work, we engineer an implantable microsphere system optimized for the controlled release of BMP-7 as a bioinspired therapeutic device against GICs. This microsphere delivery system is based on the formation of a heparin- BMP-7 nanocomplex, first coated with Tetronic® and further entrapped in a biodegradable polyester matrix. The obtained microspheres can efficiently encapsulate BMP-7, and release it in a controlled manner with minimum burst effect for over two months while maintaining protein bioactivity. Released BMP-7 showed a remarkable capacity to stop tumor formation in a GICs cell culture model, an effect that could be mediated by forced reprogramming of tumorigenic cells towards a non-tumorigenic astroglial lineage.engCancer initiating cellsGlioblastomaControlled releaseBone morphogenetic proteinMicrospheresPLGAMaterias::Investigación::32 Ciencias médicasMaterias::Investigación::33 Ciencias tecnológicas::3312 Tecnología de materiales::331299 Otras (biomateriales)journal article10.1016/j.biomaterials.2013.12.001open access