Bioengineered sequential growth factor delivery stimulates brain tissue regeneration after stroke

Yuanfei Wang; Michael J Cooke; Nadia Sachewsky; Cindi M Morshead; Molly S Shoichet

doi:10.1016/j.jconrel.2013.07.032

Bioengineered sequential growth factor delivery stimulates brain tissue regeneration after stroke

J Control Release. 2013 Nov 28;172(1):1-11. doi: 10.1016/j.jconrel.2013.07.032. Epub 2013 Aug 9.

Authors

Yuanfei Wang¹, Michael J Cooke¹, Nadia Sachewsky², Cindi M Morshead³, Molly S Shoichet⁴

Affiliations

¹ Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada; Institute of Biomaterials and Biomedical Engineering, 164 College Street, Room 407, Toronto, ON M5S 3G9, Canada.
² Department of Surgery, University of Toronto, 160 College Street, Room 1006, Toronto, ON M5S 3E1, Canada.
³ Department of Surgery, University of Toronto, 160 College Street, Room 1006, Toronto, ON M5S 3E1, Canada; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6, Canada.
⁴ Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada; Institute of Biomaterials and Biomedical Engineering, 164 College Street, Room 407, Toronto, ON M5S 3G9, Canada; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6, Canada. Electronic address: molly.shoichet@utoronto.ca.

PMID: 23933523
DOI: 10.1016/j.jconrel.2013.07.032

Abstract

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.

Keywords: Controlled delivery; Epidermal growth factor; Erythropoietin; Hydrogel composite; Stroke; Tissue regeneration.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Absorbable Implants
Animals
Brain / drug effects*
Brain / physiology
Brain / physiopathology
Delayed-Action Preparations / chemistry
Drug Delivery Systems / methods*
Epidermal Growth Factor / administration & dosage*
Epidermal Growth Factor / therapeutic use
Erythropoietin / administration & dosage*
Erythropoietin / therapeutic use
Humans
Lactic Acid / chemistry
Male
Methylcellulose / chemistry
Mice
Mice, Inbred C57BL
Nanoparticles / chemistry
Polyglycolic Acid / chemistry
Polylactic Acid-Polyglycolic Acid Copolymer
Recombinant Proteins / administration & dosage
Recombinant Proteins / therapeutic use
Regeneration
Stroke / drug therapy*
Stroke / physiopathology
Stroke / surgery

Substances

Delayed-Action Preparations
Recombinant Proteins
Erythropoietin
Polylactic Acid-Polyglycolic Acid Copolymer
Polyglycolic Acid
Lactic Acid
Epidermal Growth Factor
Methylcellulose