Novel formulation of fibroblast growth factor-2 in a hyaluronan gel accelerates fracture healing in nonhuman primates

Recent advances in understanding the biology of fracture healing and the av ailability of specific macromolecules has resulted in the development of no vel treatments for injuries to bone. Fibroblast growth factor-2 or basic fi broblast growth factor (4 mg/ml), a potent mitogen, and hyaluronan (20 mg/m l), an extracellular matrix component, were combined into a viscous gel for mulation intended for direct, percutaneous injection into fresh fractures. In an experimental primate fracture model, a bilateral l-mm-gap osteotomy w as surgically created in the fibulae of baboons. A single direct administra tion of this hyaluronan/fibroblast growth factor-2 formulation to the defec t site significantly promoted local fracture healing as evidenced by increa sed callus formation and mechanical strength. Radiographic analysis showed that the callus area was statistically significantly larger at the treated sites than at the untreated sites. Specimens treated with 0.1, 0.25, and 0. 75 mi hyaluronan/fibroblast growth factor-2 demonstrated a 48, 50, and 34% greater average load at failure and an 82, 104, and 66% greater energy to f ailure than the untreated controls, respectively. By histologic analysis, t he callus size, periosteal reaction, vascularity, and cellularity were cons istently more pronounced in the treated osteotomies than in the untreated c ontrols. These results suggest that hyaluronan/fibroblast growth factor-2 m ay provide a significant advance in the treatment of fractures.