In primates and in primates only, heterotopic bone induction is initiated by BMPs/OPs and TGF-βs as well as by sintered highly crystalline hydroxyapatites with a specific geometric configuration [2, 9, 10, 12, 40]. This indicates that in the primate, heterotopic ossicles develop as a mosaic structure, and that members of the TGF-β superfamily singly, synergistically and synchronously initiate and maintain the developing morphological structures, playing different roles at different time points of the morphogenetic cascade [2, 9, 10, 12].
Importantly, predictable osteogenesis in clinical contexts may be engineered for treatment of bone defects using delivery systems that initiate osteogenesis with relatively low doses of recombinant morphogens [2, 10–12, 49]. The intrinsic osteoinductivity regulated by the geometry of the substratum in the absence of exogenously applied osteogenic proteins of the TGF-β superfamily is helping to engineer morphogenetic responses for therapeutic osteogenesis [2, 9–12, 40, 46, 47]. The versatile nature of these biomimetic biomaterials makes them more practical and more cost effective in their clinical application than devices requiring the combination of both biomaterial matrices and DNA recombinantly produced BMPs/OPs [10, 11].