title: Tuning physical properties and BMP-2 release rates of injectable hydrogel systems for an optimal bone regeneration effect.
abstract: For a substance to be used as a drug delivery carrier and tissue inducible material for a target disease, its drug release rate and physical properties should be optimized to facilitate the healing process. We developed multi-tunable hydrogel systems with various physical properties and release behaviors to determine the optimal conditions for bone regeneration. Five injectable poly(phosphazene) hydrogels were developed with different types and amounts of anionic side-chains. The five polymer hydrogels showed considerably different in vitro and in vivo performances for sol-gel phase transition, dissolution/degradation, water uptake, and pore size. Furthermore, bone morphogenetic protein-2 (BMP-2) was loaded into the polymer hydrogels by forming nano-sized ionic-complexes with each polymer. The five types of nanocomplex hydrogels showed completely different BMP-2 release rates. By administering each nanocomplex hydrogel to mouse calvarial, we identified the most adapted nanocomplex hydrogel system for effective bone regeneration. The BMP-2 release rate was the most important factor in effective bone regeneration. Finally, the bone regeneration effect of the optimized hydrogel system was investigated in a critical-sized calvarial defect model.
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: 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: D020341:Absorbable Implants; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000737:chemistry; D001861:Bone Regeneration / Q000187:drug effects / Q000502:physiology*; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D004058:Diffusion; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry*; D007267:Injections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry; D012887:Skull Fractures / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D003692:Delayed-Action Preparations; D020100:Hydrogels; D053769:Nanocapsules
keywords: Bone morphogenetic protein-2 (BMP-2); Bone regeneration; Controlled BMP-2 release rate; Injectable hydrogel; Poly(phosphazene); Tuning physical properties