Miyakoshi Naohisa, Kobayashi Moto, Nozaka Koji, Okada Kyoji, Shimada Yoichi, Itoi Eiji
Department of Orthopedic Surgery, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Arch Orthop Trauma Surg. 2005 Dec;125(10):683-92. doi: 10.1007/s00402-005-0052-y. Epub 2005 Sep 28.
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.
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.
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).
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.
包括碱性成纤维细胞生长因子（bFGF）在内的生长因子有望成为促进骨软骨修复的有效工具。然而，需要合适的载体将生长因子输送到损伤部位。我们评估了关节内注射bFGF与透明质酸（HA）对骨软骨修复的影响以及HA在该治疗中的潜在载体作用。
在兔股骨内侧髁制造骨软骨缺损，并接受单次或每周一次关节内注射bFGF（1或10微克），有无HA。给药前，将bFGF与HA或载体生理盐水在4℃孵育24小时。首次注射后四周，处死动物，对缺损进行大体评估（12分制）和组织学评估（16分制）。还比较了单次注射含bFGF的HA与已知的含bFGF明胶微球（GM）载体的效果。
单独每周注射bFGF会引发不良副作用，如炎症反应和骨赘形成。然而，每周注射1微克bFGF与HA在大体和组织学检查中产生的骨软骨修复效果明显优于单独的每种治疗，且副作用最小（P<0.05）。与载体对照组相比，单次注射含bFGF的HA而非含bFGF的GM显示出明显更好的骨软骨修复效果（P<0.05）。
低剂量bFGF与HA对兔骨软骨修复有效。与含bFGF的GM相比，bFGF与HA显著的骨软骨修复作用可能是由于HA的潜在载体作用以及这两种药物之间可能的协同作用。HA与bFGF的组合显著抑制了单独使用bFGF产生的副作用。
