Effects of intraarticular administration of basic fibroblast growth factor with hyaluronic acid on osteochondral defects of the knee in rabbits.
BACKGROUND
Growth factors including basic fibroblast growth factor (bFGF) are expected to be useful tools for enhancing osteochondral repair. However, suitable carriers are required to deliver a growth factor to the injury site. We evaluated the effects of intraarticular injection of bFGF with hyaluronic acid (HA) on osteochondral repair and the potential carrier role of HA in this treatment.


METHODS
Osteochondral defect was created in the medial femoral condyle of rabbits and received single or weekly intraarticular injection of bFGF (1 or 10 microg) with or without HA. Prior to the administration, bFGF was incubated with HA or vehicle-saline for 24 h at 4 degrees C. Four weeks after the initial injection, the animals were killed and the defect was evaluated grossly (12-point scale) and histologically (16-point scale). The effect of single injection of bFGF (1 microg) with HA was also compared to that of the carrier known as gelatin microspheres (GM) incorporating bFGF.


RESULTS
Weekly-administered bFGF alone induced undesirable side effects such as inflammatory responses and osteophyte formation. However, weekly-administered 1 mug of bFGF with HA yielded significantly better osteochondral repair than each treatment alone in gross and histological examinations with minimal side effects (P < 0.05). Single administration of 1 microg bFGF with HA but not GM incorporating bFGF showed significantly better osteochondral repair comparing to the vehicle control (P < 0.05).


CONCLUSIONS
Low-dose bFGF with HA was effective for osteochondral repair in rabbits. The significant osteochondral reparative role of bFGF with HA comparing with GM incorporating bFGF might be explained by the potential carrier role of HA and possible synergistic action between these two agents. The combination of HA with bFGF significantly suppressed the side effects resulting from single use of bFGF.
Miyakoshi
Naohisa
N
Department of Orthopedic Surgery, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan. miyakosh@doc.med.akita-u.ac.jp
Kobayashi
Moto
M
Nozaka
Koji
K
Okada
Kyoji
K
Shimada
Yoichi
Y
Itoi
Eiji
E
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D002356:Cartilage / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D004195:Disease Models, Animal; D004338:Drug Combinations; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D007270:Injections, Intra-Articular; D007718:Knee Injuries / Q000188:drug therapy* / Q000473:pathology; D011817:Rabbits
D000276:Adjuvants, Immunologic; D004338:Drug Combinations; D016222:Fibroblast Growth Factor 2; D006820:Hyaluronic Acid