ABSTRACT
The induction of bone formation starts by erecting scaffolds of insoluble signals or substrata controlling the expression and synthesis of the soluble osteogenic molecular signals of the transforming growth factor-β (TGF-β) supergene family.1-6 There is no bone formation without the osteogenic soluble molecular signals of the TGF-β supergene family.3,4
The induction of bone formation requires three key components:4-6 (1) soluble osteogenic molecular signals; (2) responding stem cells; and (3) insoluble signals or substrata. The latter is the scaffold upon which differentiating and transforming mesenchymal stem cells erect “Bone: Formation by Autoinduction.”7,8 Last century research has thought us a fundamental truth in bone tissue engineering and regenerative medicine at large,8-10 insoluble signals or substrata, when recombined or reconstituted with soluble osteogenic molecular signals, trigger the ripple-like cascade of tissue induction and morphogenesis.1,2,4-6
The induction of bone formation by recombining or reconstituting osteogenic soluble molecular signals with insoluble signals or substrata has been pivotal for setting the rules of the tissue engineering paradigm and regenerative medicine at large;
5.1 Induction of Bone Formation and the Tissue Engineering Paradigm ............85 5.2 Biomimetism, Biomimetic Matrices, and the Induction of Bone Formation .....87 5.3 Surgical Perspectives of Self-Inducing Functional Biomimetic Matrices ......98 Acknowledgments ....................................................................................................99 References ................................................................................................................99
FIGURE 5.1 Tissue induction and morphogenesis by combinatorial molecular protocols whereby highly puriŒed osteogenic protein fractions puriŒed greater than 50,000-fold by sequential chromatography on hydroxyapatite Ultrogel adsorption and heparin-Sepharos e afŒnity chromatography followed by gel Œltration chromatography on tandem S-200 Sephacryl columns were reconstituted with discs of coral-derived macroporous constructs and implanted in the subcutaneous space of Long-Evans rats;23 tissue specimens harvested on days 7 and 12 after heterotopic implantation were processed for undecalciŒed histology and embedded in historesin.23 (a) and (b) Lower power microphotographs on day 7 highlighting the pronounced vascular invasion within the macroporous spaces surrounded by differentiating mesenchymal condensations populated by contiguous osteoblasts facing the invading central capillaries of Trueta’s deŒnition,24 the “osteogenetic vessels” (blue arrows).
