FOR MORE THAN 30 YEARS, the orthopedic community, including academic, industrial, and government sectors, has been investigating the use of synthetic-, growth factor-, and cell-based therapies as bone graft substitutes; the ultimate goal of which is to reduce or eliminate the use of autograft in healing bony defects. Synthetic bone graft substitutes, demineralized bone matrix, and bone morphogenetic proteins are legally marketed bone graft substitutes; however, each of these products has a distinct regulatory classification and, as such, requires a different regulatory path for approval prior to marketing.