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Ugo Ripamonti

Publications and source records attributed to Ugo Ripamonti.

8 recordsLinked to original sources
PubMed2006

Soluble and insoluble signals and the induction of bone formation: molecular therapeutics recapitulating development.

The osteogenic molecular signals of the transforming growth factor-beta (TGF-beta) superfamily, the bone morphogenetic/osteogenic proteins (BMPs/OPs) and uniquely in primates the TGF-beta isoforms per se, pleiotropic members of the TGF-beta supergene family, induce de novo endochondral bone formation as a recapitulation of embryonic development. Naturally derived BMPs/OPs and gamma-irradiated human recombinant osteogenic protein-1 (hOP-1) delivered by allogeneic and xenogeneic insoluble collagenous matrices initiate de novo bone induction in heterotopic and orthotopic sites of the primate Papio ursinus, culminating in complete calvarial regeneration by day 90 and maintaining the regenerated structures by day 365. The induction of bone by hOP-1 in P. ursinus develops as a mosaic structure with distinct spatial and temporal patterns of gene expression of members of the TGF-beta superfamily that singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis. The temporal and spatial expressions of TGF-beta1 mRNA indicate a specific temporal transcriptional window during which expression of TGF-beta1 is mandatory for successful and optimal osteogenesis. Highly purified naturally derived bovine BMPs/OPs and hOP-1 delivered by human collagenous bone matrices and porous hydroxyapatite, respectively, induce bone formation in mandibular defects of human patients. By using healthy body sites as bioreactors it is possible to recapitulate embryonic developments by inducing selected biomaterials combined with recombinant proteins to transform into custom-made prefabricated bone grafts for human reconstruction. The osteogenic proteins of the TGF-beta superfamily, BMPs/OPs and TGF-betas, the last endowed with the striking prerogative of inducing endochondral bone formation in primates only, are helping to engineer skeletal reconstruction in molecular terms.

Animals↗
PubMed2006

Pleiotropism of bone morphogenetic proteins: from bone induction to cementogenesis and periodontal ligament regeneration.

Bone morphogenetic and osteogenic proteins (BMPs/OPs), pleiotropic members of the transforming growth factor-beta (TGF-beta) supergene family, induce de novo endochondral bone formation and act as soluble signals of tissue morphogenesis, sculpting the architecture of multicellular mineralized structures, including the periodontal tissues. The presence of multiple forms of BMPs/OPs has a therapeutic significance and the choice of a suitable protein will be a formidable challenge to the practising periodontologist. Amino acid sequence variations in the carboxy terminal domain, the molecular basis of the structure/activity profile of each isoform, confer specialized and pleiotropic activities to each morphogenetic protein. Naturally derived BMPs/OPs regenerate cementum and alveolar bone in mandibular furcation defects of the primate Papio ursinus. Tissue morphogenesis induced by hOP-1 and hBMP-2 is qualitatively different when the morphogens are applied singly, indicating that the structure/activity profile amongst BMPs/OPs is controlling pleiotropic tissue induction and morphogenesis. Furcation defects of Papio ursinus with root surfaces exposed long-term to periodontal pathogens and filled with granulation tissue after inoculation of a pathogenetic human strain of Porphyromonas gingivalis twice a month for 12 months were implanted with hOP-1 osteogenic devices. Six months after surgery there was regeneration of alveolar bone and induction of cementogenesis, with Sharpey's fibres uniting the regenerated bone to the newly formed cementum. Although within the natural milieu of the bone matrix a plurality of morphogens may be required to initiate the cascade of pattern formation and the attainment of tissue form and function, recombinant y-irradiated hOP-1 delivered by a xenogeneic collagenous matrix induces complete periodontal tissue regeneration on periodontally affected root surfaces, showing an additional specific function of hOP-1 for tissue morphogenesis in clinical contexts. The pleiotropy of the signalling molecules of the TGF-beta superfamily is additionally highlighted by the redundancy of molecular signals initiating endochondral bone induction by the TGF-beta isoforms per se, powerful inducers of endochondral bone, but in the primate only. A novel approach in periodontal tissue regeneration is to induce heterotopic bone to be transplanted as morcellised autogenous grafts into established periodontal defects. The induction of bone develops a mosaic structure in which the osteogenic proteins of the TGF-beta superfamily singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis, with specific roles at different time points of the morphogenetic cascade.

Animals↗
PubMed2005

Soluble osteogenic molecular signals and the induction of bone formation.

The induction of bone formation starts by erecting scaffolds of smart biomimetic matrices acting as insoluble signals affecting the release of soluble osteogenic molecular signals. The cascade of bone differentiation by induction develops as a mosaic structure singly initiated by the osteogenic proteins of the transforming growth factor-beta (TGF-beta) supergene family. The osteogenic signals when combined with an insoluble signal or substratum initiate de novo bone formation by induction and are deployed singly, synergistically and synchronously to sculpt the architecture of the mineralized bone/bone marrow organ. The osteogenic proteins of the TGF-beta superfamily are the common molecular initiators deployed for embryonic development and the induction of bone in postnatal osteogenesis, whereby molecules exploited in embryonic development are re-deployed in postnatal tissue morphogenesis as a recapitulation of embryonic development. The pleiotropy of the osteogenic proteins of the TGF-beta superfamily is highlighted by the apparent redundancy of molecular signals initiating bone formation by induction including the TGF-beta isoforms per se, powerful inducers of endochondral bone but in the primate only. Bone induction by the TGF-beta isoforms in the primate is site and tissue specific with substantial endochondral bone induction in heterotopic sites but with absent osteoinductivity in orthotopic calvarial sites on day 30 and only limited osteogenesis pericranially on day 90. Ebaf/Lefty-A, a novel member of the TGF-beta superfamily, induces chondrogenesis in calvarial defects of Papio ursinus and bone regeneration across the defect on day 30 and 90, respectively. The strikingly pleiotropic effects of the bone morphogenetic and osteogenic proteins (BMPs/OPs) spring from amino acid sequence variations in the carboxy-terminal domain and in the transduction of distinct signalling pathways by individual Smad proteins after transmembrane serine/threonine kinase complexes of type I and II receptors. Predictable bone regeneration in clinical contexts requires information concerning the expression and cross regulation of gene products of the TGF-beta superfamily. OP-1, BMP-3, TGF-beta1 and type IV collagen mRNAs expression correlates to the morphological induction and maintenance of engineered ossicles by the hOP-1 osteogenic devices in the non-human primate P. ursinus. Amino-acid sequence variations amongst BMPs/OPs in the carboxy terminal domain confer the structure/activity profile responsible for the pleiotropic activity that controls tissue induction and morphogenesis of a variety of tissues and organs by different BMPs/OPs which are helping to engineer skeletal tissue regeneration in molecular terms.

Animals↗
PubMed2005

Bone morphogenetic proteins in craniofacial and periodontal tissue engineering: experimental studies in the non-human primate Papio ursinus.

The bone morphogenetic and osteogenic proteins (BMPs/OPs), pleiotropic members of the transforming growth factor-beta (TGF-beta) supergene family act as soluble signals for the de novo initiation of bone formation, sculpting the multicellular mineralized structures of the bone-bone marrow organ. The strikingly pleiotropic effects of BMPs/OPs spring from amino acid sequence variations in the carboxy-terminal domain and in the transduction of distinct signalling pathways by individual Smad proteins after transmembrane serine/threonine kinase complexes of type I and II receptors. BMPs/OPs are the common molecular initiators deployed for embryonic development and the induction of bone formation and regeneration in postnatal osteogenesis. Naturally derived BMPs/OPs extracted and purified from baboon and bovine bone matrices induce complete regeneration of non-healing calvarial defects in the non-human primate Papio ursinus as well as the induction of cementogenesis and the morphogenesis of a periodontal ligament system with a faithful insertion of Sharpey's fibers into the newly formed cementum. gamma-Irradiated recombinant human osteogenic protein-1 (hOP-1) delivered by xenogeneic bovine collagenous bone matrices completely regenerated and maintained the architecture of the induced bone after treatment of calvarial defects with single applications of doses of 0.1, 0.5 and 2.5mg hOP-1 per gram of carrier matrix. The long-term implantation of hOP-1 delivered by gamma-irradiated bovine bone matrices induced the regeneration of the three essential components of the periodontium, i.e. cementum, periodontal ligament and alveolar bone. The osteogenic proteins of the TGF-beta superfamily are sculpting tissue constructs that engineer skeletal tissue regeneration in molecular terms. The pleiotropy of the signalling molecules of the TGF-beta superfamily is highlighted by the redundancy of molecular signals initiating bone formation, including the TGF-beta isoforms per se, powerful inducers of endochondral bone formation but in the primate only. The induction of bone develops a mosaic structure in which members of the TGF-beta superfamily singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis.

Animals↗
PubMed2002

Tissue engineering: TGF-beta superfamily members and delivery systems in bone regeneration.

The induction of bone formation requires three parameters that interact in a highly regulated process: soluble osteoinductive signals, capable responding cells, and a supporting matrix substratum or insoluble signal. The use of recombinant and naturally derived bone morphogenetic proteins and transforming growth factor beta(s) (TGF-beta(s)) has increased our understanding of the functions of these morphogens during the induction of endochondral bone formation. In addition, growing understanding of the cellular interactions of living tissues with synthetic biomaterials has led to the in vivo induction of bone formation using porous biomimetic matrices as an alternative to the use of autografts for bone regeneration. This review outlines the basis of bone tissue engineering by members of the TGF-beta superfamily, focusing on their delivery systems and the intrinsic induction of bone formation by specific biomimetic matrices with a defined geometry.

Animals↗
PubMed2002

Human segmental mandibular defects treated with naturally derived bone morphogenetic proteins.

Bone induction with extracted and partially purified, naturally derived bone morphogenetic proteins (BMPs) has been demonstrated repeatedly in heterotopic and orthotopic sites of non-human primates. This spawned the investigation of bone regeneration in mandibular defects of human patients with naturally derived BMPs and was compared with osteogenesis in patients treated with autologous bone grafts (ABGs). The osteogenic device (OD) was formulated as a combination of human demineralized bone matrix as delivery system reconstituted with naturally derived BMPs. BMPs were extracted from bovine bone with chaotropic agents and purified by sequential chromatography. Thirteen patients with segmental mandibular defects were enrolled in the trial, 6 of whom received the OD and 7 the ABGs. Defects were reconstructed with a preformed titanium mesh. The OD was combined with sterile saline and applied to the defects as a paste. Autologous bone from the iliac crest was prepared as a cortico-cancellous bone graft and loaded into the titanium mesh. Patients were followed-up clinically and radiographically at 1 and 6 weeks, 3, 6, and 12-month post-implantation. A trephine biopsy of the implants was performed at 3 months post-implantation and the specimens examined on serial undecalcified sections. Histological examination showed that the OD induced bone in 2 of 6 patients treated. Histological examination of successful implanted OD exhibited mineralized bone trabeculae with copious osteoid seams lined by contiguous osteoblasts. Bone deposition directly onto non-vital matrix provided unequivocal evidence of osteoinduction. Of the 7 patients grafted with ABGs, 5 had histological evidence of osteogenesis. Morphometric analysis of the histological sections showed that, when successful, OD-treated defects had highly active osteogenesis compared with ABGs. Whilst this trial provides valuable insights for the use of BMPs in mandibular reconstruction further work is required to produce an OD that will perform reliably in clinical contexts.

Adolescent↗
PubMed2002

Comparison of two Hologic DXA systems (QDR 1000 and QDR 4500/A) for in vivo bone mass measurement in the baboon (Papio ursinus).

Dual-energy X-ray absorptiometry (DXA) is the gold standard for bone mass measurement in humans. New generation osteodensitometers have been introduced and numerous studies have been performed to compare new and old devices for in vivo measurements of bone mineral density (BMD). However similar studies in nonhuman primates have yet to be performed. In this longitudinal study, two generation of osteodensitometers from the same manufacturer (Hologic QDR 1000 and Hologic QDR 4500/A) were used to detect bone changes in a cohort of 24 ovariectomized (OVX) Chacma baboons (Papio ursinus) during a period of 36 mo. Correlation between the same osteodensitometers were also obtained for the lumbar spine (L1-L4) area, BMD, and bone mineral content (BMC) in a cohort of 33 adult female baboons and for the total hip area, BMD, and BMC in a group of 25 adult female baboons. The QDR 1000 to QDR 4500/A area, BMC, and BMD correlation coefficient (r(2)) were 0.848, 0.939, and 0.916, respectively; r(2) for total hip BMD was 0.818. Percentage of variation (PV) among the total vertebral (L1-L4) area measured by the two osteodensitometers was 5.3 +/- 2.3 (mean +/- SD). BMC had the lowest PV and the highest r(2). The mean lumbar BMD was higher when measured by QDR 1000 with a PV% of 7.7 +/- 3.1 (mean +/- SD). The mean hip BMD was higher measured by QDR 1000 with a PV% of 9.3 +/- 7.1 (mean +/- SD). Slopes of two regression lines for the lumbar spine (L1-L4) and total hip BMD were 0.928 and 0.914, respectively. Longitudinal analysis of lumbar BMD in OVX baboons showed that QDR 4500/A detected a significant bone density increase at 36 and 48 mo post- OVX, compared to time 12, whereas the QDR 1000 did not. Our results indicate that both osteodensitometers can be used to measure bone changes in longitudinal studies in primates, but that before upgrading to a newgeneration osteodensitometer, a calibration curve has to be obtained so that both devices can be equally used in regular experimental study in nonhuman primates.

Absorptiometry, Photon↗