Journal
JOURNAL OF CONTROLLED RELEASE
Volume 209, Issue -, Pages 67-76Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2015.04.023
Keywords
Polymeric nanoparticles; Dual interactions; Injectable hydrogel; Bone morphogenetic protein-2 (BMP-2); Sustained BMP-2 release
Funding
- Korea Institute of Science and Technology (KIST)
- National Research Foundation of Korea
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Localized and continuous osteogenic stimulation to defected sites is required for effective bone regeneration. Here, we suggest an injectable and sustained bone morphogenetic protein-2 (BMP-2) release system using thermosensitive polymeric nanoparticles bearing dual interacting forces with BMP-2. For sustained BMP-2 release, hydrophobic and ionic interactions were introduced to thermosensitive poly(phosphazene). Hydrophobic isoleucine ethyl ester and hydrophilic poly-ethylene glycol were mainly substituted to the poly(phosphazene) back bone for amphiphilicity and hydrophobic interaction with BMP-2. Carboxylic acid moiety was additionally substituted to the back bone for ionic interaction with BMP-2. These dual interacting polymeric nanoparticles (D-NPs) formed compact nanocomplexes with BMP-2. The aqueous solution of BMP-2/D-NP nanocomplexes was transformed to hydrogel when the temperature of the solution increased. Loaded BMP-2 was sustain-released for three weeks from the BMP-2/D-NP nanocomplex hydrogel. The extended BMP-2 exposure caused higher osteocalcin secretion in C2C12 cells. Significant bone generations were observed at the target site by single injection of BMP-2/D-NP nanocomplexes in vivo. (C) 2015 Elsevier B.V. All rights reserved.
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