The Role of Biologics and Bone Graft Substitutes in Spinal Fusion: Current Evidence and Future Directions
Abstract:
Successful spinal arthrodesis requires a biologically active environment, mechanical stability, and sufficient graft material. Autologous iliac crest bone remains the reference standard because it provides osteogenic cells, osteoinductive signals, and an osteoconductive scaffold, but harvest related pain, limited volume, and additional operative morbidity have accelerated the use of osteobiologics and bone graft substitutes. This narrative review evaluates current evidence for local autograft, allograft, demineralized bone matrix, ceramics, recombinant human bone morphogenetic protein-2, cellular bone matrices, bone marrow aspirate, peptide enhanced grafts, and emerging delivery systems. Recombinant human bone morphogenetic protein-2 has the strongest comparative evidence for improving fusion in selected lumbar procedures, although dose, containment, surgical approach, and adverse event profiles remain central concerns. Demineralized bone matrix and synthetic ceramics are useful graft extenders but generally depend on host biology or an additional osteogenic source. Cellular products and autologous cell concentrates are conceptually attractive, yet supporting studies remain heterogeneous and frequently industry associated. Product selection should therefore be individualized according to fusion risk, anatomic site, graft volume, regulatory status, cost, and the quality of clinical evidence. Future progress will depend on lower dose and spatially controlled growth factor delivery, reproducible cell characterization, comparative effectiveness trials, and value-based assessment rather than fusion rate alone.
KeyWords:
spinal fusion, osteobiologics, bone graft substitute, bone morphogenetic protein, demineralized bone matrix, cellular bone matrix, ceramics
References:
- Ambrosio, L., et al. (2025). Efficacy and safety of osteobiologics for lumbar spinal fusion: A systematic review and network meta-analysis. The Spine Journal. Advance online publication.
- Antonacci, C. L., et al. (2024). Use of ceramic synthetic allografts in spine surgery. Journal of Spine Surgery. Advance online publication.
- Apaydin, A. S., et al. (2024). Synthetic osteobiologics in spine surgery: A review. Journal of Spine Surgery. Advance online publication.
- Biddau, D. T., et al. (2024). Bone graft substitutes used in anterior lumbar interbody fusion: A contemporary review. Journal of Spine Surgery, 10, 687–702.
- Butler, M., et al. (2026). Understanding spine biologics: A systematic review of demineralized bone matrix in spinal fusion. Global Spine Journal. Advance online publication.
- Cheers, G. M., et al. (2024). Advances in implants and bone graft types for lumbar spinal fusion. Bone & Joint Research, 13, 456–472.
- Goldman, S. N., et al. (2024). Efficacy of an allograft cellular bone matrix as an alternative to autograft in anterior cervical discectomy and fusion. Journal of Spine Surgery, 10, 547–559.
- Imam, M. A., et al. (2017). A systematic review of the clinical applications and complications of bone marrow aspirate concentrate in orthopaedic surgery. SICOT-J, 3, 17.
- Khalid, M. U., et al. (2023). Stem cells in degenerative lumbar spine disease: A review. Journal of Spine Surgery, 9, 93–107.
- Khan, S. N., et al. (2023). Osteobiologics and value based care: Challenges and opportunities. Global Spine Journal, 13, 2417–2428.
- Lambrechts, M. J., et al. (2024). Cellular bone matrix in spine surgery: Are they worth the risk? A systematic review. Global Spine Journal, 14, 1755–1768.
- Lansford, T., et al. (2024). High lumbar spinal fusion rates using cellular bone allograft in a prospective multicenter study. International Journal of Spine Surgery, 18, 512–523.
- Lee, H. R., et al. (2024). Meta-analysis on efficacy and complications of bone morphogenetic protein-2 in posterior cervical fusion. World Neurosurgery, 181, e189–e200.
- Lee, J. H., et al. (2025). Low-dose bone morphogenetic protein use in spinal fusion: A review of efficacy and safety. Asian Spine Journal. Advance online publication.
- Lytle, E. J., et al. (2020). The minimally effective dose of bone morphogenetic protein in posterior lumbar interbody fusion: A systematic review and meta-analysis. The Spine Journal, 20(8), 1286–1304.
- Nabizadeh, N., et al. (2021). Changes in recombinant human bone morphogenetic protein-2 utilization in posterior lumbar fusion. Global Spine Journal, 11, 1127–1134.
- Salamanna, F., et al. (2024). Efficacy of using autologous cells with graft substitutes for spinal fusion: A systematic review and meta-analysis. Journal of Orthopaedic Translation, 48, 58–71.
- Seok, M. C., et al. (2024). Bone substitute options for spine fusion in patients with spine trauma, part II: The role of recombinant human bone morphogenetic protein-2. Korean Journal of Neurotrauma, 20, 1–17.
- Taman, M., et al. (2025). The role of recombinant human bone morphogenetic protein-2 in C1–2 fusion: Institutional experience and systematic review. Journal of Clinical Medicine, 14, 7648.
- U.S. Food and Drug Administration. (2025). Infuse Bone Graft: Instructions for use and approved indications. U.S. Department of Health and Human Services.
- von Benecke, J. P., et al. (2024). A narrative review on recombinant human bone morphogenetic protein-2 in spinal fusion. Journal of Spine Surgery, 10, 570–585.
- Wang, J. C., et al. (2018). Prospective randomized controlled trial of an anorganic bone mineral with P-15 peptide in anterior cervical discectomy and fusion. The Spine Journal, 18, 914–923.
- Youssef, J. A., et al. (2019). Current use of biologics in spine surgery. Global Spine Journal, 9(1 Suppl), 7S–13S.
- Zhang, H., et al. (2021). Bone graft substitutes for spinal fusion: A systematic review of clinical evidence. European Spine Journal, 30, 2199–2215.