Table 2.

Overview of Bone Graft Supplements. Mechanism of each supplement is provided along with advantages and disadvantages as provided in the current literature. TGF-β = transforming growth factor-beta; BMP = bone morphogenetic protein; MSC = mesenchymal stem cell.

Supplements	Mechanism	Advantages	Disadvantages
Bone Morphogenetic Proteins	TGF-β family cytokines that initiate SMAD pathway activating transcription factors for growth [7]	Enhances osteogenesis and oseoinduction [42], and genetic cloning capabilities make it possible to produce in large quantities [7]	At supraphysiological levels they are antagonized by BMP inhibitors [47], can cause dysphagia and airway complications [50], it is potentially oncogenic [54], and has high costs [48]
Autologous Growth Factors	Growth factors that are released from platelet degranulation that activates the proliferation of osteoblasts, fibroblasts and MSCs [61]	Can be used with autografts, allografts or ceramics to increase rates of successful fusion [62]	There is no clinical data as of this time that provides definitive evidence of an increase in the rate of spinal fusion [5]
Mesenchymal Stem Cells	Differentiate into osteoblasts and chondrocytes to promote spinal fusion [68]	Can create a graft with all the properties of osteogenesis, osteoinduction and osteoconduction [70]	Potentially leads to chronic harvesting site pain [15]
Synthetic Peptides	Amino acid sequences found in alpha-1 chains of type I collagen that enhances bone mineralization [72,73]	Fusion rates of i-FACTOR compared to autograft were slightly higher in some studies [75,76,77]	To date, there is still minimal third-party studies measuring rates of fusion
Gene Therapy	Targeting the expression of genes that encode osteoinductive and osteogenic factors [76]		Difficult to assess successful gene transduction in vivo, and, thus, its performance is difficult to measure in clinical trials [76]