Spinal fusion is a well-accepted surgical treatment for many spinal diseases; the costs amount to ~34 billion annually in the US alone, with significant increases projected due to an aging population. Non-unions are a notable complication of spinal fusion surgery. To promote bone regeneration, the FDA has approved rhBMP-2 with a rebsorbable collagen sponge as an alternative to the standard bone graft for spinal fusion. However, adverse events associated with supraphysiological doses, and burst release of rhBMP-2 is a recurring problem for clinicians. Formulations that help regulate the delivery and release profile of growth factors are needed to achieve consistent clinical outcomes. Numerous approaches have been tested, and some of them have shown promising results. Strategies tested for achieving this endeavor include: 1) optimization of cytokine kinetics, 2) combination of different growth factors, 3) utilization of osteoinductive and osteoconductive scaffolds, 4) incorporation of progenitor cells, 5) augmentation of biological activity with tropic bone factors, and, 6) reduction of the endogenous BMP antagonists.