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World J Biol Chem. May 26, 2010; 1(5): 109-132
Published online May 26, 2010. doi: 10.4331/wjbc.v1.i5.109
Soluble and insoluble signals sculpt osteogenesis in angiogenesis
Ugo Ripamonti
Ugo Ripamonti, Bone Research Unit, Medical Research Council/University of the Witwatersrand, Johannesburg, Medical School, 7 York Road, 2193 Parktown, South Africa
Author contributions: Ripamonti U solely contributed to this paper.
Supported by South African Medical Research Council, University of the Witwatersrand, Johannesburg and the National Research Foundation of South Africa
Correspondence to: Ugo Ripamonti, MD, PhD, Professor, Director, Bone Research Unit, Medical Research Council/University of the Witwatersrand, Johannesburg, Medical School, 7 York Road, 2193 Parktown, South Africa. ugo.ripamonti@wits.ac.za
Telephone: +27-11-7172144 Fax: +27-11-7172300
Received: April 23, 2010
Revised: May 17, 2010
Accepted: May 24, 2010
Published online: May 26, 2010
Abstract

The basic tissue engineering paradigm is tissue induction and morphogenesis by combinatorial molecular protocols whereby soluble molecular signals are combined with insoluble signals or substrata. The insoluble signal acts as a three-dimensional scaffold for the initiation of de novo tissue induction and morphogenesis. The osteogenic soluble molecular signals of the transforming growth factor-β (TGF-β) supergene family, the bone morphogenetic/osteogenic proteins (BMPs/OPs) and, uniquely in the non-human primate Papio ursinus (P. ursinus), the three mammalian TGF-β isoforms induce bone formation as a recapitulation of embryonic development. In this paper, I discuss the pleiotropic activity of the BMPs/OPs in the non-human primate P. ursinus, the induction of bone by transitional uroepithelium, and the apparent redundancy of molecular signals initiating bone formation by induction including the three mammalian TGF-β isoforms. Amongst all mammals tested so far, the three mammalian TGF-β isoforms induce endochondral bone formation in the non-human primate P. ursinus only. Bone tissue engineering starts by erecting scaffolds of biomimetic biomaterial matrices that mimic the supramolecular assembly of the extracellular matrix of bone. The molecular scaffolding lies at the hearth of all tissue engineering strategies including the induction of bone formation. The novel concept of tissue engineering is the generation of newly formed bone by the implantation of “smart” intelligent biomimetic matrices that per se initiate the ripple-like cascade of bone differentiation by induction without exogenously applied BMPs/OPs of the TGF-β supergene family. A comprehensive digital iconographic material presents the modified tissue engineering paradigm whereby the induction of bone formation is initiated by intelligent smart biomimetic matrices that per se initiate the induction of bone formation without the exogenous application of the soluble osteogenic molecular signals. The driving force of the intrinsic induction of bone formation by bioactive biomimetic matrices is the shape of the implanted substratum. The language of shape is the language of geometry; the language of geometry is the language of a sequence of repetitive concavities, which biomimetizes the remodelling cycle of the primate osteonic bone.

Keywords: Induction of bone formation, Bone morphogenetic proteins, Osteogenic proteins, Transforming growth factor-β proteins, Primates, Uroepithelial osteogenesis, Redundancy, Synergistic induction of bone formation, Biomimetic smart bioactive matrices