Introduction: Identification of patients at risk of developing non-union and institution of procedures preventing non-union could be attractive in routine fracture management. We investigated whether recombinant human bone morphogenetic protein (rhBMP-2) delivered in a hyaluronic acid carrier could prevent non-union development in an experimental non-union model, which simulates the clinical situation of open mid-tibial fractures. Methods: Sixteen rabbits underwent a standard non-union operation comprising midtibial osteotomy, excision of periosteum and endosteum, and plate fixation. Before closure of the wound eight rabbits received interfragmentary deposition of 200 mu g rhBMP-2 delivered in a hyaluronan get carrier, and eight rabbits received get carrier alone. Results: After 7 weeks, torsional failure moment of the osteotomy and energy absorbed at failure, macroscopic and radiographic appearance, callus area, and interfragmentary bone volume fraction confirmed that rhBMP-2 delivery significantly improved bone heating. Blood flow at the osteotomy site, measured using radiolabelled microspheres, was not higher in the united osteotomies than in non-united osteotomies. Discussion: rhBMP-2 delivered in a hyaluronic acid carrier-induced formation of competent bone in an experimental model of compromised heating. We, therefore, propose interfragmentary deposition of rhBMP-2 delivered in a hyaluronic acid carrier to patients encountering fractures at risk of non-union or delayed union. (c) 2004 Elsevier Ltd. All rights reserved.