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The limitations of autologous and alloplastic reconstruction for craniofacial bone defects have created a clinical need for viable tissue-engineering strategies. Recombinant human bone morphogenetic protein-2 (rhBMP-2) has shown promise in this setting. The aim of this study was to determine the long-term biomechanical properties of rhBMP-2–mediated calvarial reconstruction.Twelve-week-old New Zealand White rabbits underwent subtotal calvarectomy. Defects were repaired in one of several groups: immediate reconstruction with autologous graft, immediate reconstruction with cryopreserved bone graft, immediate reconstruction with rhBMP-2 (favorable), and delayed reconstruction with rhBMP-2 following infection and subsequent débridement (unfavorable). Cryopreserved reconstructions were measured at 6 weeks; autologous reconstructions were measured at 6 weeks and 6 months; and both favorable and unfavorable rhBMP-2 reconstructions were assessed at 6 weeks, 6 months, and 1 year after reconstruction. Healing was assessed with computed tomography. An unconfined compression test was performed for biomechanical analysis. Stress at 20 percent strain, percentage relaxation, tangent modulus, and final strain at 1800 N were compared between groups.Nearly complete radiographic coverage was achieved by 6 months for autologous reconstruction and by 6 weeks for rhBMP-2 reconstruction. Favorable rhBMP-2 reconstruction demonstrated a larger final strain at 1800 N through 1 year compared with native bone. Bone in unfavorable rhBMP-2 reconstruction was more compressible than native bone, with a larger final strain at 1800 N at 1 year. There were no significant differences between favorable and unfavorable groups.Despite providing radiographic coverage, the biomechanical properties of rhBMP-2 bone differ from those of native bone. Further studies are warranted to determine how these properties affect overall strength and structural integrity.