TY - JOUR
T1 - Direct delayed human adenoviral BMP-2 or BMP-6 gene therapy for bone and cartilage regeneration in a pony osteochondral model
AU - Menendez, M. I.
AU - Clark, D. J.
AU - Carlton, M.
AU - Flanigan, D. C.
AU - Jia, G.
AU - Sammet, S.
AU - Weisbrode, S. E.
AU - Knopp, M. V.
AU - Bertone, A. L.
N1 - Funding Information:
Dr Bertone is supported by ARY920101. This project was supported by The Trueman Endowment , The Wright Center for Innovation in Biomedical Imaging and the Ohio State University Sports Medicine Internal Grants Program.
PY - 2011/8
Y1 - 2011/8
N2 - Objective: To evaluate healing of surgically created large osteochondral defects in a weight-bearing femoral condyle in response to delayed percutaneous direct injection of adenoviral (Ad) vectors containing coding regions for either human bone morphogenetic proteins 2 (BMP-2) or -6. Methods: Four 13. mm diameter and 7. mm depth circular osteochondral defects were drilled, 1/femoral condyle (n= 20 defects in five ponies). At 2 weeks, Ad-BMP-2, Ad-BMP-6, Ad-green fluorescent protein (GFP), or saline was percutaneously injected into the central drill hole of the defect. Quantitative magnetic resonance imaging (qMRI) and computed tomography (CT) were serially performed at 12, 24, and 52 weeks. At 12 (one pony) or 52 weeks, histomorphometry and microtomographic analyses were performed to assess subchondral bone and cartilage repair tissue quality. Results: Direct delivery of Ad-BMP-6 demonstrated delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and histologic evidence of greater Glycosaminoglycan (GAG) content in repair tissue at 12 weeks, while Ad-BMP-2 had greater non-mineral cartilage at the surface at 52 weeks (p< 0.04). Ad-BMP-2 demonstrated greater CT subchondral bone mineral density (BMD) by 12 weeks and both Ad-BMP-2 and -6 had greater subchondral BMD at 52 weeks (p< 0.05). Despite earlier (Ad-BMP-6) and more persistent (Ad-BMP-2) chondral tissue and greater subchondral bone density (Ad-BMP-2 and -6), the tissue within the large weight-bearing defects at 52 weeks was suboptimal in all groups due to poor quality repair cartilage, central fibrocartilage retention, and central bone cavitation. Delivery of either BMP by this method had greater frequency of subchondral bone cystic formation (p< 0.05). Conclusions: Delivery of Ad-BMP-2 or Ad-BMP-6 via direct injection supported cartilage and subchondral bone regeneration but was insufficient to provide long-term quality osteochondral repair.
AB - Objective: To evaluate healing of surgically created large osteochondral defects in a weight-bearing femoral condyle in response to delayed percutaneous direct injection of adenoviral (Ad) vectors containing coding regions for either human bone morphogenetic proteins 2 (BMP-2) or -6. Methods: Four 13. mm diameter and 7. mm depth circular osteochondral defects were drilled, 1/femoral condyle (n= 20 defects in five ponies). At 2 weeks, Ad-BMP-2, Ad-BMP-6, Ad-green fluorescent protein (GFP), or saline was percutaneously injected into the central drill hole of the defect. Quantitative magnetic resonance imaging (qMRI) and computed tomography (CT) were serially performed at 12, 24, and 52 weeks. At 12 (one pony) or 52 weeks, histomorphometry and microtomographic analyses were performed to assess subchondral bone and cartilage repair tissue quality. Results: Direct delivery of Ad-BMP-6 demonstrated delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and histologic evidence of greater Glycosaminoglycan (GAG) content in repair tissue at 12 weeks, while Ad-BMP-2 had greater non-mineral cartilage at the surface at 52 weeks (p< 0.04). Ad-BMP-2 demonstrated greater CT subchondral bone mineral density (BMD) by 12 weeks and both Ad-BMP-2 and -6 had greater subchondral BMD at 52 weeks (p< 0.05). Despite earlier (Ad-BMP-6) and more persistent (Ad-BMP-2) chondral tissue and greater subchondral bone density (Ad-BMP-2 and -6), the tissue within the large weight-bearing defects at 52 weeks was suboptimal in all groups due to poor quality repair cartilage, central fibrocartilage retention, and central bone cavitation. Delivery of either BMP by this method had greater frequency of subchondral bone cystic formation (p< 0.05). Conclusions: Delivery of Ad-BMP-2 or Ad-BMP-6 via direct injection supported cartilage and subchondral bone regeneration but was insufficient to provide long-term quality osteochondral repair.
KW - Bone morphogenetic protein
KW - Cartilage healing
KW - Computed tomography
KW - Gene delivery
KW - Magnetic resonance imaging
UR - http://www.scopus.com/inward/record.url?scp=79960323461&partnerID=8YFLogxK
U2 - 10.1016/j.joca.2011.05.007
DO - 10.1016/j.joca.2011.05.007
M3 - Article
C2 - 21683796
AN - SCOPUS:79960323461
SN - 1063-4584
VL - 19
SP - 1066
EP - 1075
JO - Osteoarthritis and Cartilage
JF - Osteoarthritis and Cartilage
IS - 8
ER -