Lack of effect on bone healing of injectable BMP-2 augmented hyaluronic acid

Abstract

Autologous bone graft is the gold standard for the filling of large osseous defects. Because of its limited supply and complications such as pain, bleeding or infection, the development of alternative bone substitutes has been the subject of several studies. In clinical practice, the most commonly used bone substitutes are calcium phosphates like hydroxyapatite or tricalcium phosphate. With the aim to improve the osseointegration of these materials, growth factors such as bone morphogenetic protein-2 (BMP-2) have been added. Preferably, an injectable bone substitute should be made available. Hyaluronic acid is a component of the extracellular matrix of many tissues, including bone. We examined the bone regenerative effect of commercially available, injectable hyaluronic acid (Hyalart) with and without addition of bone morphogenetic protein-2 (BMP-2). Trepanation defects of 9.4 mm diameter in the intercondylar groove of sheep femora were filled with pure and augmented (200 microg BMP-2) hyaluronic acid. As controls, empty defects and defects treated with autologous bone graft harvested from the contralateral side were used. After 3 months, the defects were analysed by fluorescence microscopy after intravital fluorescence staining, contact microradiography, histology and histomorphometry. Treatment of the defects with loaded and unloaded hyaluronic acid resulted in a significant lack of bone formation inside the defects. Untreated defects showed an amount of 5.1% newly formed bone, and defects treated with autologous bone graft revealed a bone content of 20%. The difference between both groups was statistically significant (P < 0.05). Furthermore, there was neither a remarkable effect in the periphery of the defects nor ectopic bone formation. The application of the used injectable hyaluronic acid (Hyalart) with and without BMP-2 is not advantageous as sole bone substitute for the filling of osseous defects.