Potentiation of the activity of bone morphogenetic protein-2 in bone regeneration by a PLA-PEG/hydroxyapatite composite.
Bone morphogenetic proteins (BMPs) are biologically active molecules capable of inducing new bone formation, and show potential for clinical use in bone defect repair. However, an ideal system for delivering BMPs that can potentiate their bone-inducing ability and provide initial mechanical strength and scaffold for bone ingrowth has not yet been developed. In this study, to construct a carrier/scaffold system for BMPs, we combined two biomaterials: interconnected-porous calcium hydroxyapatite ceramics (IP-CHA), and the synthetic biodegradable polymer poly D,L,-lactic acid-polyethyleneglycol block co-polymer (PLA-PEG). We used a rabbit radii model to evaluate the bone-regenerating efficacy of rhBMP-2/PLA-PEG/IP-CHA composite. At 8 weeks after implantation, all bone defects in groups treated with 5 or 20 microg of BMP were completely repaired with sufficient strength. Furthermore, using this carrier scaffold system, we reduced the amount of BMP necessary for such results to about a tenth of the amount needed in previous studies, probably due to the superior osteoconduction ability of IP-CHA and the optimal drug delivery system provided by PLA-PEG, inducing new bone formation in the interconnected pores. The present findings indicate that the synthetic biodegradable polymer/IP-CHA composite is an excellent combination carrier/scaffold delivery system for rhBMP-2, and that it strongly promotes the clinical effects of rhBMP-2 in bone tissue regeneration.
Kaito
Takashi
T
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. t-kaito@let.eonet.ne.jp
Myoui
Akira
A
Takaoka
Kunio
K
Saito
Naoto
N
Nishikawa
Masataka
M
Tamai
Noriyuki
N
Ohgushi
Hajime
H
Yoshikawa
Hideki
H
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000737:chemistry; D001861:Bone Regeneration / Q000187:drug effects*; D018786:Bone Substitutes / Q000008:administration & dosage / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004343:Drug Implants / Q000737:chemistry; D017102:Fracture Healing / Q000187:drug effects / Q000502:physiology; D006882:Hydroxyapatites / Q000737:chemistry*; D007773:Lactates / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011817:Rabbits; D011885:Radius Fractures / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery*; D023822:Tissue Engineering / Q000379:methods; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D004337:Drug Carriers; D004343:Drug Implants; D006882:Hydroxyapatites; D007773:Lactates; D016212:Transforming Growth Factor beta; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols