期刊
JOURNAL OF CONTROLLED RELEASE
卷 172, 期 1, 页码 1-11出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2013.07.032
关键词
Stroke; Tissue regeneration; Controlled delivery; Hydrogel composite; Epidermal growth factor; Erythropoietin
资金
- Heart and Stroke Foundation
- Natural Science and Engineering Research Council
- Ontario Neurotrauma Foundation
- Stem Cell Network
Stroke is a leading cause of disability with no effective regenerative treatment. One promising strategy for achieving tissue repair involves the stimulation of endogenous neural stem/progenitor cells through sequential delivery of epidermal growth factor (EGF) followed by erythropoietin (EPO). Yet currently available delivery strategies such as intracerebroventricular (ICV) infusion cause significant tissue damage. We designed a novel delivery system that circumvents the blood brain barrier and directly releases growth factors to the brain. Sequential release of the two growth factors is a key in eliciting tissue repair. To control release, we encapsulate pegylated EGF (EGF-PEG) in poly(lactic-co-glycolic acid) (PLGA) nanoparticles and EPO in biphasic microparticles comprised of a PLGA core and a poly(sebacic acid) coating. EGF-PEG and EPO polymeric particles are dispersed in a hyaluronan methylcellulose (HAMC) hydrogel which spatially confines the particles and attenuates the inflammatory response of brain tissue. Our composite-mediated, sequential delivery of EGF-PEG and EPO leads to tissue repair in a mouse stroke model and minimizes damage compared to ICV infusion. (C) 2013 Elsevier B. V. All rights reserved.
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