A new biotechnology for articular cartilage repair: subchondral implantation of a composite of interconnected porous hydroxyapatite, synthetic polymer (PLA-PEG), and bone morphogenetic protein-2 (rhBMP-2).
OBJECTIVE
Articular cartilage repair remains a major obstacle in tissue engineering. We recently developed a novel tool for articular cartilage repair, consisting of a triple composite of an interconnected porous hydroxyapatite (IP-CHA), recombinant human bone morphogenetic protein-2 (rhBMP-2), and a synthetic biodegradable polymer [poly-d,l-lactic acid/polyethylene glycol (PLA-PEG)] as a carrier for rhBMP-2. In the present study, we evaluated the capacity of the triple composite to induce the regeneration of articular cartilage.


METHODS
Full-thickness cartilage defects were created in the trochlear groove of 52 New Zealand White rabbits. Sixteen defects were filled with the bone morphogenetic protein (BMP)/PLA-PEG/IP-CHA composite (group I), 12 with PLA-PEG/IP-CHA (group II), 12 with IP-CHA alone (group III), and 12 were left empty (group IV). The animals were killed 1, 3, and 6 weeks after surgery, and the gross appearance of the defect sites was assessed. The harvested tissues were examined radiographically and histologically.


RESULTS
One week after implantation with the BMP/PLA-PEG/IP-CHA composite (group I), vigorous repair had occurred in the subchondral defect. It contained an agglomeration of mesenchymal cells which had migrated from the surrounding bone marrow either directly, or indirectly via the interconnecting pores of the IP-CHA scaffold. At 6 weeks, these defects were completely repaired. The regenerated cartilage manifested a hyaline-like appearance, with a mature matrix and a columnar organization of chondrocytes.


CONCLUSIONS
The triple composite of rhBMP-2, PLA-PEG, and IP-CHA promotes the repair of full-thickness articular cartilage defects within as short a period as 3 weeks in the rabbit model. Hence, this novel cell-free implant biotechnology could mark a new development in the field of articular cartilage repair.
Tamai
Noriyuki
N
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Myoui
Akira
A
Hirao
Makoto
M
Kaito
Takashi
T
Ochi
Takahiro
T
Tanaka
Junzo
J
Takaoka
Kunio
K
Yoshikawa
Hideki
H
D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D001861:Bone Regeneration / Q000187:drug effects / Q000502:physiology; D002357:Cartilage Diseases / Q000188:drug therapy* / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology*; D019902:Chondrocytes / Q000187:drug effects / Q000502:physiology; D004337:Drug Carriers; D017886:Durapatite / Q000008:administration & dosage*; D007773:Lactates / Q000008:administration & dosage*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology; D008855:Microscopy, Electron, Scanning / Q000379:methods; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
C525718:BMP2 protein, human; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D007773:Lactates; D016212:Transforming Growth Factor beta; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols; D017886:Durapatite