Local BMP-7 release from a PLGA scaffolding-matrix for the repair of osteochondral defects in rabbits.
The use of tissue engineering to repair large osteochondral defects has been impeded by the limited regenerative capacity of cartilage. Herein, we describe the local release of bone morphogenetic protein 7 (BMP-7) to stimulate the bone marrow-derived progenitors to repair osteochondral defects. BMP-7-releasing poly(D,L-lactide-co-glycolide) (PLGA) matrix was specially designed to retain the dual-function of local BMP-7 release and progenitor-scaffolding with its defect-fitting architecture. To optimize the release kinetics during the repair period, BMP-7/PLGA film was cast on the surface of a cylindrical PLGA matrix. The matrix demonstrated a release profile of BMP-7 in a sustained manner over 28 days, maintaining its biological activity. The cylindrical PLGA matrices loaded with BMP-7 were implanted into the osteochondral defects (2 mm in diameter, 3 mm in depth) in rabbit knees. Histological observations revealed that neo-cartilage generation was completed in a well-integrated morphology with its surrounding normal cartilage and subchondral bone at 12 weeks post-implantation. Partial degradation of the PLGA matrix during the repair period guided neo-cartilage formation, which verified the effective scaffolding function of the matrix. Regenerated cartilage in BMP-7-treated defects stained positive for type II collagen and glycosaminoglycan (GAG). Adjacent BMP-7-untreated defects were also repaired with cartilage regeneration, suggesting the effect of local BMP-7 release in the synovial fluid. The BMP-7-unloaded PLGA matrix demonstrated guided cartilage regeneration to a certain extent, whereas the adjacent defects without the matrix revealed only fibrous tissue infiltration. These results indicated that a strategy employing the combined functions of local BMP-7 release and the cell scaffolding of a PLGA matrix might be a potential modality for osteochondral repair.
Department of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, Republic of Korea.
Mi Ra
MR
Jung
In Kyong
IK
Shim
Hye Jin
HJ
Chung
Hye Rim
HR
Lee
Yoon Jeong
YJ
Park
Myung Chul
MC
Lee
Young Il
YI
Yang
Sun Hee
SH
Do
Seung Jin
SJ
Lee
D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000008:administration & dosage* / Q000737:chemistry; D001861:Bone Regeneration / Q000187:drug effects*; D002356:Cartilage / Q000187:drug effects* / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D005269:Femur / Q000293:injuries; D006025:Glycosaminoglycans / Q000378:metabolism; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D054457:Tissue Scaffolds
D055419:Bone Morphogenetic Protein 7; D024043:Collagen Type II; D006025:Glycosaminoglycans; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid