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M Heliotis

Publications and source records attributed to M Heliotis.

10 recordsLinked to original sources

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Clinical Competence↗

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↗

Transformation of a prefabricated hydroxyapatite/osteogenic protein-1 implant into a vascularised pedicled bone flap in the human chest.

We describe the intramuscular transformation of a hydroxyapatite/osteogenic protein-1 (HA/OP-1) composite implant, into a vascularised pedicled bone flap useful for reconstruction of a hemi-mandible. Extraskeletal induction of a bone flap for transplantation was achieved without the addition of harvested bone, bone marrow, or stem cells. Five months after apparent clinical success, an MRSA infection of the graft led to its failure. The background to ectopically induced bone flaps is introduced, with our experience in a human case presented. The results from this emerging biotechnology are discussed in the light of limited human clinical experience.

Bone Morphogenetic Protein 7↗

Fresh frozen bone in femoral impaction grafting: can developments in bone regeneration improve on this?

Major advances in the understanding of bone regeneration have led to revolutionary applications of bone conduction and induction. Revision hip surgery is on the increase with an active, ageing population demanding increased quality of life. The technically demanding instrumentation and materials necessary for revision prosthetic hip replacements have been rapidly incorporated into clinical practice. Unfortunately, advantage has not been taken of the basic and fundamental principles of bone induction and regeneration, available for many years now. In impaction grafting for revision hip replacements where fresh frozen bone is currently used as a standard, we argue and demonstrate from the literature why this technique is biologically inferior to the results which potentially can be gained by exploiting osteoinductive grafts such as demineralised bone matrix, hydroxyapetite, and inductive factors such as bone morphogenetic proteins.

Animals↗

Induction of cementogenesis by recombinant human osteogenic protein-1 (hop-1/bmp-7) in the baboon (Papio ursinus).

Recombinant human osteogenic protein-1 (hOP-1), a member of the bone morphogenetic protein family, was examined for its efficacy in periodontal regeneration. Twelve furcation defects, surgically prepared in the first and second mandibular molars, were treated with bovine insoluble collagenous matrix in conjunction with 0.0 (control), 100 and 500 mu g of recombinant hOP-1 per g of matrix. After 60 days of healing, histological and histometric analyses on serial, undemineralized sections cut at 7 mu m showed substantial cementogenesis on the exposed dentine of furcations treated with both doses of hOP-1 (p < 0.01 vs control). Foci of nascent mineralization were seen within the newly deposited cementoid along the coronal areas of hOP-1-treated defects. Within the furcations, there were substantial amounts of residual collagenous carrier, interspersed with a mineralized matrix having histological features of cementum. This mineralized cementum-like material was predominantly deposited around the carrier, and blended into newly formed cementum along the root surfaces. In the apical area, the cementum-like material and the remaining alveolar bony housing were not connected; indeed the two components were separated by a fibrovascular tissue that had numerous features of the periodontal ligament space. Formation and insertion of Sharpey's fibres into newly formed root cementum were also observed. It is likely that the expression of specific cell phenotypes by hOP-1 is regulated, in part, by the extracellular matrix microenvironment, including dentine. Thus, exposed dentine, in the presence of exogenous hOP-1 at the doses tested, may preferentially modulate the expression of the cementogenic phenotype. These findings in a non-human primate show that hOP-1, at the doses tested, induced cementogenesis on surgically denuded root surfaces, indicating a specific function during repair and regeneration of periodontal tissues.

Alveolar Process↗