Introduction

Abstract

Bone has a remarkable potential to regenerate upon fracture. Marshall Urist discovered that non-living demineralized bone could become fully mineralized living functional bone when implanted at ectopic sites, and he coined this phenomenon ‘bone by auto-induction’ [1]. He hypothesized that the principle behind this regenerative potential resides in the extracellular matrix of bone and termed it ‘bone morphogenetic proteins (BMPs)’. While the identity of BMP has been illusive for a long time, the demonstration that the proteins responsible for bone induction could be extracted from extracellular matrix of bone and assayed reproducibly for their activity by reconstituting them with an appropriate collagen scaffold and implanting at ectopic sites in rats permitted the molecular cloning and identification of ‘bona fide’ BMPs [2–4]. This knowledge represents, for the first time, a prototype demonstration of tissue engineering in vivo and has been attributed to three biological components as prerequisites for bone tissue engineering: signaling molecules, responding cells and scaffold/microenvironment. The collagen carrier serves as substratum for migration and proliferation of mesenchymal stem cells (osteoprogenitors) and BMP signals their differentiation into fully vascularized functional bone [5, 6].