Reconsidering Osteoconduction in the Era of Additive Manufacturing.

Bone regeneration procedures in clinics and bone tissue engineering stand on three pillars: osteoconduction, osteoinduction, and stem cells. In the last two decades, the focus in this field has been on osteoinduction, which is realized by the use of bone morphogenetic proteins and the application of mesenchymal stem cells to treat bone defects. However, osteoconduction was reduced to a surface phenomenon because the supposedly ideal pore size of osteoconductive scaffolds was identified in the 1990s as 0.3-0.5 mm in diameter, forcing bone formation to occur predominantly on the surface. Meanwhile, additive manufacturing has evolved as a new tool to realize designed microarchitectures in bone substitutes, thereby enabling us to study osteoconduction as a true three-dimensional phenomenon. Moreover, by additive manufacturing, wide-open porous scaffolds can be produced in which bone formation occurs distant to the surface at a superior bony defect-bridging rate enabled by highly osteoconductive pores 1.2 mm in diameter. This review provides a historical overview and an updated definition of osteoconduction and related terms. In addition, it shows how additive manufacturing can be instrumental in studying and optimizing osteoconduction of bone substitutes, and provides novel optimized features and boundaries of osteoconductive microarchitectures. Impact Statement This review updates the definition of osteoconduction and draws clear lines to discriminate between osteoconduction, osseointegration, and osteoinduction. Moreover, additively manufactured libraries of scaffolds revealed that: osteoconduction is more a three-dimensional than a surface phenomenon; microarchitecture dictates defect bridging, which is the measure for osteoconduction; pore diameter or the diagonal of lattice microarchitectures of osteoconductive bone substitutes should be ∼1.2 mm.