Figure 9.

The crux of the problem of bone tissue engineering and regenerative medicine in clinical context. Can we engineer an activated bioreactor that spontaneously, and/or intrinsically initiate the ripple-like cascade of bone differentiation by induction, without the exogenous application of the osteogenic soluble molecular signals of the transforming growth factor-β (TGF-β) supergene family? (Ripamonti, 2003) and when implanted in human patient synthesize per se “Bone: formation by autoinduction?” (Urist, 1965). The undecalcified images presented in (A,B) show that the above is possible, that hydroxyapatite coated titanium geometric constructs per se initiate the spontaneous induction of bone formation in primate models (Ripamonti et al., 2012a) and without the exogenous application of the osteogenic soluble molecular signals of the TGF-β supergene family. (A) High power view of a concavity of hydroxyapatite-coated titanium construct (white arrow) harvested from the rectus abdominis muscle of Papio ursinus. Light blue arrow indicates the induction of mineralized newly formed bone (darker blue) surfaced by an osteoid seam (magenta arrow) surfacing the mineralized bone. (B) In another inductive concavity identical morphological patterns of induction with newly formed mineralized bone (light blue arrow) surfaced by a large osteoid seam. Undecalcified sections cut at 30 μm using the Exakt diamond saw grinding and polishing equipment (Ripamonti et al., 2012a).