Enhancement of ectopic bone formation by bone morphogenetic protein-2 released from a heparin-conjugated poly(L-lactic-co-glycolic acid) scaffold.
In this study, a heparin-conjugated poly(l-lactic-co-glycolic acid) (HP-PLGA) scaffold was developed for the sustained delivery of bone morphogenetic protein-2 (BMP-2), and then used to address the hypothesis that BMP-2 delivered from this scaffold could enhance ectopic bone formation. We found the amount of heparin conjugated to the PLGA scaffolds could be increased up to 3.2-fold by using scaffolds made from star-shaped PLGA, as compared to scaffolds made from linear PLGA, and that the release of BMP-2 from the HP-PLGA scaffold was sustained for at least 14 days in vitro. The BMP-2 released from the HP-PLGA scaffold stimulated an increase in alkaline phosphatase (ALP) activity of osteoblasts for 14 days in vitro, suggesting that the HP-PLGA scaffold delivery system releases BMP-2 in a bioactive form for a prolonged period. By contrast, BMP-2 release from unmodified (no heparin) PLGA scaffolds induced a transient increase in ALP activity for the first 3 days and a decrease thereafter. In vivo bone formation studies showed the BMP-2-loaded HP-PLGA scaffolds induced bone formation to a much greater extent than did either BMP-2-loaded unmodified PLGA scaffolds or unloaded (no BMP-2) HP-PLGA scaffolds, with 9-fold greater bone formation area and 4-fold greater calcium content in the BMP-2-loaded HP-PLGA scaffold group compared to the BMP-2-loaded unmodified PLGA scaffold group. Collectively, these results demonstrate that the HP-PLGA delivery system is capable of potentiating the osteogenic efficacy of BMP-2, and underscore its importance as a possible bone regeneration strategy.
Jeon
Oju
O
Department of Chemical Engineering, Hanyang University, Sungdong-Gu, Seoul, Korea.
Song
Su Jin
SJ
Kang
Sun-Woong
SW
Putnam
Andrew J
AJ
Kim
Byung-Soo
BS
D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology*; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006493:Heparin / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D019344:Lactic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D018482:Muscle, Skeletal / Q000166:cytology; D010012:Osteogenesis / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D016062:Porosity; D019736:Prostheses and Implants; D051381:Rats; D017208:Rats, Wistar; D023822:Tissue Engineering / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology*
C525718:BMP2 protein, human; D001672:Biocompatible Materials; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011108:Polymers; D016212:Transforming Growth Factor beta; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006493:Heparin; D002118:Calcium