Neural restoration has been proved to be difficult after brain stroke especially in its later stage.This is mainly due to the generation of an unpropitious niche in the injured area, including loss of vascular support but production of numerous inhibitors for neuronal regeneration.Reconstruction of a proper niche for promoting local angiogenesis therefore, should be a key approach for neural restoration after stroke.In present study, a new biomaterial composite which could be implanted in injured area of the brain was created for experimental therapy of brain ischemia in the mouse.This composite was using a hyaluronic acid (HA) based biodegradable hydrogel scaffold, mixed with poly(lactic-co-glycolic acid) (PLGA) microspheres containing VEGF and Ang-1, the factors of stimulating angiogenesis.In addition, the antibody of Nogo receptor (NgR-Ab), which can bind to multiple inhibitory myelin proteins and promote neural regeneration, was covalently attached to the hydrogel, for making the hydrogel more bioactive and suitable for neural survives.This composite (HA-PLGA) was implanted into the mouse model with middle cerebral artery occlusion (MCAO), to explore a new approach for restoration of brain function after ischemia.A good survival and proliferation of human umbilicalartery endothelial cells (HUAECs) and neural stem cells (NSCs) were seen on the HA hydrogel with PLGA microspheres in vitro.This new material was shown to have good compatibility with the brain tissue and inhibition to gliosis and inflammation, after its implantation in the normal or ischemic brain of mice.Particularly, a good angiogenesis was found around the implanted HA-PLGA hydrogel, and the mouse models showed clearly a behavior improvement.The results in present study indicate therefore, that the HA-PLGA hydrogel is a promising material which is able to induce angiogenesis in ischemic region by releasing VEGF and Ang-1, thus create a suitable niche for neural restoration in later stage of stroke.