Axonal Loss in Murine Peripheral Nerves Following Exposure to Recombinant Human Bone Morphogenetic Protein-2 in an Absorbable Collagen Sponge

Abstract

With the proven efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) to treat open tibial fractures and promote spine fusion, there has been an increase in its off-label use. Recent studies have shown that BMPs play a role in nerve development and regeneration. Little is known about changes that result when rhBMP-2 is used in the vicinity of peripheral nerves. The purpose of this study is to characterize changes in peripheral nerves following exposure to rhBMP-2-soaked collagen sponges. rhBMP-2 on an absorbable collagen sponge (ACS) was implanted directly on the sciatic nerves of Wistar rats. One and three weeks following surgery, the nerves were harvested and histological analysis was performed to evaluate inflammatory and structural changes. rhBMP-2-soaked collagen sponges induced ectopic bone formation in muscle tissue in all animals after three weeks, but did not cause bone formation within the nerve. Axonal swelling and splitting of the myelin sheath were observed in both experimental and control nerves and may be a result of surgical manipulation. The overall incidence of axonal loss was 15.8% in the rhBMP-2/ACS-exposed nerves and was 0% in control nerves (p < 0.05). rhBMP-2-soaked collagen sponges may adversely affect the axons of peripheral nerves by causing axonal dropout and loss of axons. Ectopic bone formation occurs within muscle tissues and not within the peripheral nerve. The axonal dropout may be a direct effect of rhBMP-2-soaked collagen sponges and not nerve compression as it was observed prior to ectopic bone formation.