Orthotopic bone formation by implantation of apatite-coated poly(lactide-co-glycolide)/hydroxyapatite composite particulates and bone morphogenetic protein-2.
Bone morphogenetic proteins (BMPs) are the most potent osteoinductive growth factors. However, a delivery system is essential to take advantage of the osteoinductive effect of BMPs. In the present study, we tested the suitability of apatite-coated poly(D,L-lactide-co-glycolide)/nanohydroxyapatite (PLGA/HA) particulates as carriers for the controlled release of BMP-2. The release of BMP-2 from apatite-coated PLGA/HA particulates was sustained for at least 4 weeks in vitro. A delivery system of apatite-coated PLGA/HA particulates suspended in fibrin gel further slowed the BMP-2 release rate. In vivo implantation of either Fibrin gel + BMP-2 or Fibrin gel + apatite-coated PLGA/HA particulates showed enhanced new bone formation in critical-sized calvarial defects of rats 8 weeks after implantation, compared to implantation of fibrin gel only. Importantly, new bone formation was much higher in the defects treated with BMP-2 delivery using apatite-coated PLGA/HA particulates in fibrin gel (Fibrin gel + PLGA/HA + BMP-2 group) than in the defects treated either with apatite-coated PLGA/HA particulates in fibrin gel (Fibrin gel + BMP-2 group) or with BMP-2 delivery using fibrin gel alone (Fibrin gel + BMP-2 group). BMP-2 and osteoinductive HA had an additive effect on orthotopic bone formation. In conclusion, the apatite-coated PLGA/HA particulates showed good results as carriers for BMP-2. The BMP-2 delivery system showed high osteogenic capability in a rat calvarial bone defect model. The local and sustained delivery system for BMP-2 developed in this study may be useful as a carrier for BMP-2 and would enhance bone regeneration efficacy for the treatment of large bone defects.
Kim
Sang-Soo
SS
Department of Bioengineering, Hanyang University, Seoul 133-791, Korea. bskim@hanyang.ac.kr
Gwak
So-Jung
SJ
Kim
Byung-Soo
BS
D000818:Animals; D001826:Body Fluids; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002113:Calcification, Physiologic / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D004337:Drug Carriers / Q000494:pharmacology; D004343:Drug Implants / Q000494:pharmacology; D017886:Durapatite / Q000494:pharmacology*; D005337:Fibrin / Q000494:pharmacology; D005782:Gels; D019344:Lactic Acid / Q000494:pharmacology*; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D004343:Drug Implants; D005782:Gels; D016212:Transforming Growth Factor beta; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005337:Fibrin; D017886:Durapatite