Browsing by Author "Ripamonti, Ugo"

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    Growth and morphogenetic factors in bone induction: role of osteogenin and related bone morphogenetic proteins in craniofacial and periodontal bone repair.
    (1992) Ripamonti, Ugo; Reddi, A. H.
    Bone has considerable potential for repair as illustrated by the phenomenon of fracture healing. Repair and regeneration of bone recapitulate the sequential stages of development. It is well known that demineralized bone matrix has the potential to induce new bone formation locally at a heterotopic site of implantation. The sequential development of bone is reminiscent of endochondral bone differentiation during bone development. The collagenous matrix-induced bone formation is a prototype model for matrix-cell interactions in vivo. The developmental cascade includes migration of progenitor cells by chemotaxis, attachment of cells through fibronectin, proliferation of mesenchymal cells, and differentiation of bone. The bone inductive protein, osteogenin, was isolated by heparin affinity chromatography. Osteogenin initiates new bone formation and is promoted by other growth factors. Recently, the genes for osteogenin and related bone morphogenetic proteins were cloned and expressed. Recombinant osteogenin is osteogenic in vivo. The future prospects for bone induction are bright, and this is an exciting frontier with applications in oral and orthopaedic surgery.
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    The morphogenesis of bone in replicas of porous hydroxyapatite obtained from conversion of calcium carbonate exoskeletons of coral
    (1991-06) Ripamonti, Ugo
    The morphogenesis of bone in a porous hydroxyapatite substratum was studied after intramuscular implantation in adult primates. Replicas of porous hydroxyapatite that had been obtained after hydrothermal conversion of the calcium carbonate exoskeleton of coral (genus Goniopora) were implanted intramuscularly in twenty-four adult male baboons (Papio ursinus). Serial sections from specimens that had been harvested at three, six, and nine months showed that initially the formation of fibrous connective tissue was characterized by a prominent vascular component and by condensations of collagen fibers assembled at the interface of the hydroxyapatite. The morphogenesis of bone was intimately associated with the differentiation of the connective-tissue condensations. Bone formed without an intervening endochondral phase. Although the amount of bone varied considerably, in several specimens extensive bone developed, filling large portions of the porous spaces and culminating in total penetration by bone within the implants. The mean volume fraction composition of the specimens was 20.8 +/- 1.0 per cent (mean and standard error) for bone, 17.3 +/- 1.7 per cent for connective-tissue condensation, 31.9 +/- 1.0 per cent for fibrovascular tissue, 6.4 +/- 0.6 per cent for bone marrow, and 34.6 +/- 0.5 per cent for the hydroxyapatite framework. The amount of bone and marrow increased at each time-period, and the hydroxyapatite framework was significantly reduced between six and nine months. This indicated a moderate biodegradation over time, which was possibly a result of incomplete conversion of carbonate to hydroxyapatite. Linear regression analysis showed a negative correlation between the hydroxyapatite framework and the magnitude of bone formation within the porosities of the hydroxyapatite (p = 0.0001). Biochemical coating of the hydroxyapatite substratum with an allogeneic fibrin-fibronectin protein concentrate prepared from baboon plasma did not significantly increase the amount of bone formation within the porous spaces. The hydroxyapatite substratum may have functioned as a solid-phase domain for anchorage of bone morphogenetic proteins.
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    Osteogenic competence and potency of the bone induction principle inductive substrates that initiate bone formation by autoinduction
    Ripamonti, Ugo; Duarte, Raquel ; Ferretti, Carlo ; Reddi, H.
    The de novo induction of bone has always been a fascinating phenomenon, keeping skeletal reconstructionists and cellular developmental biologists continuously engaged to finally provide a molecular and cellular approach to the induction of bone formation. A significant advancement was made by the purification and cloning of the human recombinant bone morphogenetic proteins, members of the transforming growth factor-b supergene family. Human bone morphogenetic proteins are powerful inducers of bone in animal models including nonhuman primates. Translation in clinical contexts has however, proven to be surprisingly difficult. This review also describes the significant induction of bone formation by the human transforming growth factor-b3 when implanted in heterotopic intramuscular sites of the Chacma baboon Papio ursinus. Large mandibular defects implanted with 250mg human transforming growth factor-b3 in human patients showed significant osteoinduction; however, the induction of bone was comparatively less than the induction of bone in P ursinus once again highlighting the conundrum of human osteoinduction: is the bone induction principle failing clinical translation?