Effects of Basic Fibroblast Growth Factor on the Repair of Large Osteochondral Defects of Articular Cartilage in Rabbits: Dose–Response Effects and Long-Term Outcomes

Abstract

Articular cartilage possesses a limited capacity for self-renewal. The regenerated tissue often resembles fibrocartilage-like tissue rather than hyaline cartilage, and degeneration of the articular surface eventually occurs. The purpose of this study was to investigate the effect of basic fibroblast growth factor (bFGF) on the healing of full-thickness articular cartilage defects. bFGF (0, 10, 50, 100, 250, 500, or 1000 ng) was mixed with collagen gel and implanted into full-thickness articular cartilage defects drilled into rabbit knees. The repaired tissue was examined grossly and histologically, and was evaluated with the use of a grading scale at 4, 12, 24, and 50 weeks. At 4 weeks, treatment with 100 ng of bFGF had greatly stimulated cartilage repair both grossly and histologically in comparison with untreated defects (those filled with plain collagen gel). The average total scores on the histological grading scale were significantly better for the defects treated with bFGF than for the untreated defects. These improvements were evident as long as 50 weeks postoperatively, although slight deterioration was noted in the repaired cartilage. Immunohistochemical staining for type II collagen showed that this cartilage-specific collagen was diffusely distributed in the repaired tissue at 50 weeks. These findings suggest that bFGF may be a practical and important candidate for use in cartilage repair.

Identification of Fibroblast Growth Factor-18 as a Molecule to Protect Adult Articular Cartilage by Gene Expression Profiling

“…Several growth factors other than Fgf18 have been reported in animal models to have anabolic effects on cartilage including insulin-like growth factor-I, osteogenic protein-1, TGF-␤, hepatocyte growth factor, and Fgf2 (35)(36)(37)(38)(39)(40)(41)(42). Although the apparent efficacy of these factors has been proved in osteochondral defect models and partial thickness chondral defect models, Fgf18 was the first reported to show the protective or regenerative effect in the surgically induced rat meniscal tear model by Moore et al (6).…”

The effect of fibroblast growth factor-2 on autologous osteochondral transplantation

“…Fujimoto et al [3] documented cartilage repair following the administration of a collagen sponge containing 700 ng of FGF-2 in a rabbit model. On the other hand, an overdose of FGF-2 induces hypertrophic arthritis [21,25]. Shida et al [21], using various doses of FGF-2, reported that the injection of more than 5 μg in normal rat knees resulted in an approximately 3-to 4.5-fold increase in articular cartilage compared to the same area of the control knee.…”

“…Basic fibroblastic growth factor (FGF-2) promotes the repair response in fullthickness articular cartilage defects and bone formation [3,4,6,17,25]. As a carrier material system, the gelatinhydrogel-incorporated growth factor leads to regeneration for cell differentiation and proliferation [24].…”

Mesenchymal Stem Cells in Tissue Engineering

“…Bioactives other than growth factors have also been studied, such as synthetic thrombin peptide-508. Much of the existing evidence of the chondroprogenitive role of these growth factors was obtained using them either alone or with cultured chondrocytes [Redini et al, 1988;Nixon et al, 1999;Hunziker et al, 2001;Hickey at al., 2003;Tanaka et al, 2004]. However, stromal cell populations have also been found to expand efficiently and/or undergo chondrogenic differentiation under the influence of many of the above-mentioned bioactive factors, such as TGF-␤ , IGF, PDGF, and FGF [Kuznetsov et al, 1997;Worster et al, 2000Worster et al, , 2001.…”

“…Adult articular cartilage retains a poor capacity for growth and regeneration, and in the limited circumstances of partial repair, it is replaced with suboptimal fibrocartilage. Recent tissue engineering advances in the augmentation of cartilage repair have included the use of autologous and allogenic chondrocyte and cartilage grafts [Lane et al, 1977;Grande et al, 1989;Wakitani et al, 1989;Minas and Peterson, 1999;Peterson et al, 2002], biomaterials [Vacanti et al, 1991;Grande et al, 1997;Sherwood et al, 2002;Cao et al, 2003], growth factors [Redini et al, 1988;Sellers et al, 1997;Nixon et al, 1999;O'Connor et al, 2000;Fukumoto et al, 2003;Tanaka et al, 2004], mesenchymal stem cells (MSCs) [Wakitani et al, 1994;Grande et al, 1995;Caplan et al, 1997;Im et al, 2001], and genetic engineering [Mason et al, 2000;Madry et al, 2002;Gelse et al, 2003;Grande et al, 2003;Noel et al, 2004]. However, the progress made with such tissue engineering techniques is still limited by our current fund of knowledge.…”