title: Sustained BMP-2 delivery and injectable bone regeneration using thermosensitive polymeric nanoparticle hydrogel bearing dual interactions with BMP-2.
abstract: 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.
authors.affiliation: Center for Biomaterials, Korea Institute of Science & Technology, Seoul 130-650, Republic of Korea; Department of Biomolecular Science, University of Science and Technology (UST), Seoul 136-791, Republic of Korea.
authors.forename: Bo-Bae
authors.initials: BB
authors.lastname: Seo
authors.affiliation: Department of Pharmacology and Dental Therapeutics, and Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Hyuck
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Pharmacology and Dental Therapeutics, and Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Jeong-Tae
authors.initials: JT
authors.lastname: Koh
authors.affiliation: Center for Biomaterials, Korea Institute of Science & Technology, Seoul 130-650, Republic of Korea; Department of Biomolecular Science, University of Science and Technology (UST), Seoul 136-791, Republic of Korea. Electronic address: scsong@kist.re.kr.
authors.forename: Soo-Chang
authors.initials: SC
authors.lastname: Song
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D065546:Drug Liberation; D020100:Hydrogels / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D007267:Injections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry; D015675:Osteocalcin / Q000378:metabolism; D011108:Polymers / Q000737:chemistry
chemical_list: D055396:Bone Morphogenetic Protein 2; D003692:Delayed-Action Preparations; D020100:Hydrogels; D009943:Organophosphorus Compounds; D011108:Polymers; C515246:poly(organophosphazene); D015675:Osteocalcin
keywords: Bone morphogenetic protein-2 (BMP-2); Dual interactions; Injectable hydrogel; Polymeric nanoparticles; Sustained BMP-2 release