Soluble, insoluble and geometric signals sculpt the architecture of mineralized tissues

Abstract

Bone morphogenetic and osteogenic proteins (BMPs/OPs), members of the transforming growth factor-β (TGF-β) superfamily, are soluble mediators of tissue morphogenesis and induce de novo endochondral bone formation in heterotopic extraskeletal sites as a recapitulation of embryonic development. In the primate Papio ursinus, the induction of bone formation has been extended to the TGF-β isoforms per se. In the primate and in the primate only, the TGF-β isoforms are initiators of endochondral bone formation by induction and act in a species-, site-and tissuespecific mode with robust endochondral bone induction in heterotopic sites but with limited new bone formation in orthotopic bone defects. The limited inductive capacity orthotopically of TGF-β isoforms is associated with expression of the inhibitory Smads, Smad6 and Smad7. In primates, bone formation can also be induced using biomimetic crystalline hydroxyapatite matrices with a specific surface geometry and without the exogenous application of osteogenic proteins of the TGF-β superfamily, even when the biomimetic matrices are implanted heterotopically in the rectus abdominis muscle. The sequence of events that directs new bone formation upon the implantation of highly crystalline biomimetic matrices initiates with vascular invasion, mesenchymal cell migration, attachment and differentiation of osteoblast-like cells attached to the substratum, expression and synthesis of osteogenic proteins of the TGF-β superfamily resulting in the induction of bone as a secondary response. The above findings in the primate indicate enormous potential for the bioengineering industry. Of particular interest is that biomimetic matrices with intrinsic osteoinductivity would be an affordable option in the local context.

Evaluation of bone ingrowth into porous titanium implant: histomorphometric analysis in rabbits

“…8,9,14,15 Changes in pore shape can also radically affect the success of bone development; the optimal morphogenetic geometry for bone ingrowth has a concave shape with specific dimensions. 23,24 New bone growth into porous metal implants also depends on factors, including interconnecting pore size, 7,25 pore throats open to the surface, 8 and the presence of gaps between the implant and bone surface. 7 However, no consensus has yet been reached regarding optimal pore structure.…”

Tissue engineering: strategies, stem cells and scaffolds

“…Scaffold architecture has been shown to modify the response of cells and subsequent tissue formation, as demonstrated by the generation of mineralization fronts in specific regions of scaffolds (Ripamonti, 2004). Nano to microscale topography has been demonstrated to affect cell behaviour by modification of cytoskeleton arrangements (Meredith et al 2007).…”

Transforming Growth Factor Beta 1 and Vascular Endothelial Growth Factor Levels in the Pathogenesis of Periodontal Disease

“…Bone morphogenetic and osteogenic proteins (BMPs/OPs), pleiotropic members of the TGF-~superfamily, induce de novo endochondral bone formation and act as soluble signals of tissue morphogenesis sculpting the multicellular mineralized structures of the bonebone marrow organ (15).…”