A biodegradable polymer as a cytokine delivery system for inducing bone formation.
Bone morphogenetic proteins (BMPs) that have the potential to elicit new bone in vivo have been used in a tissue-engineering approach for the repair of bone injuries and bone defects. Although it is now possible to generate large amounts of recombinant human (rh) BMPs for medical use, the major challenge remains in the development of optimal local delivery systems for these proteins. Here we describe the development of a synthetic biodegradable polymer, poly-d,l-lactic acid-p-dioxanone-polyethylene glycol block copolymer (PLA-DX-PEG). This polymer exhibits promising degradation characteristics for BMP delivery systems and good biocompatibility under test conditions. PLA-DX-PEG/rhBMP-2 composite implants induced ectopic new bone formation effectively when tested in vivo, and can repair large bone defects orthotopically. This polymeric delivery system represents an advance in the technology for the enhancement of bone repair.
Saito
N
N
Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. saito@hsp.md.shinshu-u.ac.jp
Okada
T
T
Horiuchi
H
H
Murakami
N
N
Takahashi
J
J
Nawata
M
M
Ota
H
H
Nozaki
K
K
Takaoka
K
K
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001846:Bone Development; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000627:therapeutic use; D001842:Bone and Bones / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000235:genetics* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D006801:Humans; D007085:Ilium / Q000378:metabolism; D007773:Lactates / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D011108:Polymers / Q000737:chemistry*; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta; D014965:X-Rays
C525718:BMP2 protein, human; D001672:Biocompatible Materials; C525719:Bmp2 protein, mouse; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016207:Cytokines; D007773:Lactates; D011108:Polymers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C432470:polylactic acid-dioxanone-polyethylene glycol block copolymer; C499469:recombinant human bone morphogenetic protein-2; D011092:Polyethylene Glycols; D003094:Collagen; D002118:Calcium