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Biomedical subjects

U Ripamonti

Publications and source records attributed to U Ripamonti.

At least 55 records · Page 3Linked to original sources
PubMed1992

Osteogenin, a bone morphogenetic protein, adsorbed on porous hydroxyapatite substrata, induces rapid bone differentiation in calvarial defects of adult primates.

Osteogenin, a bone morphogenetic protein, in conjunction with insoluble collagenous bone matrix initiates local endochondral bone differentiation by induction in vivo. This study, by exploiting the affinity of native osteogenin for hydroxyapatite, was designed to construct a delivery system for the expression of the biologic activity of osteogenin in nonhealing calvarial defects of adult primates. After exposure of the calvaria, 64 cranial defects, 25 mm in diameter, were prepared in 16 adult male baboons (Papio ursinus). Defects were implanted with disks of porous nonresorbable and resorbable hydroxyapatite substrata obtained after hydrothermal conversion of calcium carbonate exoskeletons of corals. In each animal, one disk of each hydroxyapatite preparation was treated with osteogenin isolated and purified from baboon bone matrix after sequential chromatography on heparin-Sepharose, hydroxyapatite, and Sephacryl S-200 gel filtration columns. The remaining two defects were implanted with one disk of each hydroxyapatite preparation without osteogenin as control. Histomorphometry on decalcified sections prepared on days 30 and 90 showed superior osteogenesis in osteogenin-treated nonresorbable hydroxyapatite specimens as compared with controls. On day 90, substantial bone formation also had occurred in control nonresorbable hydroxyapatite specimens. On day 90, but not on day 30, significantly greater amounts of bone had formed in osteogenin-treated resorbable specimens as compared with resorbable controls. Overall, resorbable substrata performed poorly when compared with nonresorbable substrata, perhaps due to a premature dissolution of the implants. These results provide evidence that the biologic activity of osteogenin can be restored and delivered by a substratum other than the organic collagenous matrix, inducing rapid bone differentiation in calvarial defects of adult nonhuman primates. The adsorption strategy of osteogenin on porous inorganic nonimmunogenic substrata may help to design appropriate osteogenic delivery systems for craniofacial and orthopedic applications in humans.

Adsorption↗
PubMed1992

Primate dentine extracellular matrix induces bone differentiation in heterotopic sites of the baboon (Papio ursinus).

In rodents, demineralized dentine matrix induces local differentiation of endochondral bone. This study investigated the osteoinductive potential of primate dentine matrices when implanted extraskeletally in allogeneic recipients. Demineralized dentine cylinders prepared from adult baboon incisors and demineralized dentine matrix pulverized to a particle size of 74-420 microns were implanted into the rectus abdominis of 4 subadult male baboons (Papio ursinus). Specimens were harvested 30 and 90 d after implantation. Histological analysis on serial sections showed bone differentiation in demineralized dentine cylinders after partial resorption of the external demineralized layer, and in resorption lacunae and excavation chambers within the matrix. Implants of demineralized dentine matrix of 74-420 microns particle size showed no osteoinductive activity as determined biochemically (alkaline phosphatase activity) and histologically. The demonstration of bone induction by primate dentine prepared from fully erupted tooth matrix suggests that putative osteogenic proteins may be conserved after dentinogenesis and embryonic tooth development, and may play a role during healing after surface demineralization of exposed root surfaces during regenerative procedures in humans.

Animals↗
PubMed1992

Growth and morphogenetic factors in bone induction: role of osteogenin and related bone morphogenetic proteins in craniofacial and periodontal bone repair.

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.

Alveolar Process↗
PubMed1992

Induction of bone in composites of osteogenin and porous hydroxyapatite in baboons.

A major goal of the combined effort of basic scientists and plastic and reconstructive surgeons is the development of novel bone substitutes based on osteogenic growth and differentiation factors with optimal delivery systems for skeletal repair. Osteogenin is a protein initiator of bone differentiation. The present study examined the osteogenic potential of osteogenin in combination with porous hydroxyapatite replicas obtained after hydrothermal conversion of calcium carbonate exoskeletons of corals. Bovine osteogenin, with an apparent molecular weight of 28 to 42 kDa, purified by hydroxyapatite-Ultrogel adsorption chromatography, heparin-Sepharose affinity chromatography, and HR Sephacryl S-200 molecular sieve chromatography, was delivered into rods of nonresorbable and resorbable hydroxyapatite replicas with an average porosity of 600 microns. A total of 48 rods were bioassayed for osteogenic activity by intramuscular implantation into eight adult baboons (Papio ursinus) as a prerequisite for clinical trials in humans. Bovine osteogenin fractions reconstituted with baboon insoluble collagenous bone matrix were implanted in an additional four adult baboons. Specimens were harvested at 30 and 90 days after implantation and subjected to histomorphometry and alkaline phosphatase activity determination. Differentiation of bone occurred in nonresorbable hydroxyapatite rods, both osteogenin-treated and controls. However, no bone formation was observed in resorbable rods, even in the presence of osteogenin. These results demonstrate that the surface and chemical characteristics of the substratum, independent of the osteogenic stimulus, have a profound influence on the morphogenesis of bone. The demonstration of bone induction in nonhuman primates with porous nonresorbable hydroxyapatite replicas and baboon insoluble collagenous bone matrix reconstituted with bovine osteogenin establishes the therapeutic potential of the principle of bone induction in craniofacial, periodontal, and orthopedic reconstructive surgery.

Analysis of Variance↗
PubMed1992

Advances in osteogenin and related bone morphogenetic proteins in bone induction and repair.

Bone matrix is a repository of growth and differentiation factors as demonstrated by the induction of local cartilage and bone formation in rats. The bone inductive activity, termed osteogenin, can be dissociatively extracted, and it was isolated by heparin affinity, hydroxyapatite and molecular sieve chromatography. Osteogenin has been purified to homogeneity from bovine bone matrix and the sequences of several tryptic peptides have been determined. The sequences were similar to portions of the amino acid sequence deduced from the cDNA clone of bone morphogenetic protein-3 (BMP-3). The carboxyl-terminal quarter of osteogenin has sequence identity to the corresponding regions of two related proteins BMP-2A and BMP-2B. The bone inductive proteins are members of the TGF-beta superfamily, by virtue of the location of the highly conserved cysteines in their carboxyl-terminal region. Osteogenin and related BMPs initiate cartilage and bone formation in vivo. The study of the mechanism of action of these proteins will add considerable new information on the molecular signals controlling endochondral bone formation. In vitro data indicate that osteogenin stimulates the expression of the osteogenic and chondrogenic phenotypes. Our results demonstrate their profound influence on proteoglycan synthesis and degradation in bovine cartilage explant cultures. High affinity specific binding sites have been identified in both MC3T3 cells and articular chondrocytes. In vivo experiments demonstrate the efficacy of primate osteogenin in restoring large calvarial defects in adult baboons, establishing a primary role for osteogenin in therapeutic initiation and promotion of osteogenesis.

Bone Development↗
PubMed1992

Calvarial regeneration in primates with autolyzed antigen-extracted allogeneic bone.

The limited regenerative capacity of calvarial membranous bone provides an ideal system for investigation in the comparative physiology of bone regeneration. Cranial defects, 25 mm in diameter, were created in 24 adult male baboons (Papio ursinus). In each animal, defects were implanted with chemosterilized antigen-extracted, autolyzed allogeneic (AAA) bone, grafted with iliac corticocancellous grafts, or left ungrafted to monitor the spontaneous regeneration potential of the adult baboon calvaria. Antigen-extracted, autolyzed allogeneic bone implants were prepared from donor sub-adult baboon calvariae and processed so as to retain bone morphogenetic protein (BMP) in the bone matrix. Histomorphometric analysis of undecalcified sections (7-microns thick) prepared from specimens harvested at three, six, and nine months after surgery showed superior osteogenesis in AAA bone matrix implants, compared with autografts and untreated defects. The morphogenetic response was characterized by vascular invasion and mesenchymal cell aggregation after partial resorption and dissolution of the implanted matrix, followed by bone deposition at the calvarial interfaces, the pericranial and endocranial surfaces of the implants, and within the open diploic spaces of the implanted original AAA bone matrix. The superior osteogenesis in AAA bone implants appeared consistent with extensive osteoconductive invasion from the open diploic and endosteal spaces of the recipient calvariae. In addition, the finding of a delicate, trabecularlike bone, appositional to the central areas of the implanted matrix, suggests that AAA bone implants might also have acted as inductive substratum for bone differentiation.

Analysis of Variance↗
PubMed1991

The induction of bone in osteogenic composites of bone matrix and porous hydroxyapatite replicas: an experimental study on the baboon (Papio ursinus).

This study evaluated the morphogenetic properties of osteogenic composites of bone matrix and porous coralline hydroxyapatite (HA) replicas after intramuscular implantation in adult baboons (Papio ursinus). Composite implants were prepared by inserting rods of nonresorbable HA replicas, 20 mm in length, and 5 or 7 mm in diameter, into the medullary canals of 90 diaphyseal baboon bone cylinders, 20 mm in height, sequentially extracted and chemosterilized to obtain autolysed antigen-extracted allogeneic (AAA) bone matrix, preserving the bone morphogenetic protein (BMP) activity. Composites were implanted in the rectus abdominis and in the dorsal musculature of 24 adult male baboons. Before implantation, 45 composites were coated with an allogeneic fibrin-fibronectin protein concentrate (AFFP) prepared from fresh-frozen baboon plasma. Histologic analysis of undecalcified and decalcified specimens procured at 3, 6, and 9 months showed bone differentiation by induction along the endosteal surfaces of the chemosterilized matrix and within the porous spaces of the HA substratum. Bone formation was often extensive, culminating in complete penetration of the porous spaces. Histomorphometry showed that bone in the HA substratum increased at each time period. The biochemical treatment of the composite implants with AFFP did increase significantly the amount of induced bone, although only in the HA substratum. Bone differentiation was confirmed by fluorescence microscopy of the mineralization fronts after intravital double tetracycline labeling. The differentiation of bone in composites of bone matrix and porous HA replicas in extraskeletal sites of adult baboons may help to design appropriate delivery systems for the controlled therapeutic initiation of bone formation for craniofacial and orthopedic applications in man.

Animals↗
PubMed1991

Xenogeneic osteogenin, a bone morphogenetic protein, and demineralized bone matrices, including human, induce bone differentiation in athymic rats and baboons.

Subcutaneous implantation of xenogeneic demineralized bone matrix does not initiate endochondral bone differentiation. Dissociative extraction in 4 M guanidine-HCl or 6 M urea has shown that the apparent species-specificity of intact bone matrix resides in its insoluble immunogenic component, since there is homology in solubilized osteogenic proteins amongst mammals. To further investigate the species-specificity and cross-species reactivity of bone matrix components, baboon and human demineralized bone matrix (DBM) and bovine osteogenin, purified greater than 50,000-fold and with an apparent molecular mass of 28-42 kilodaltons, were implanted in the subcutaneous space of athymic and euthymic rats and into the rectus abdominis of 16 baboons (Papio ursinus). Baboon DBM was also implanted in athymic and euthymic mice. Alkaline phosphatase activity and histology of implants harvested at day 11 and 30 showed that baboon and human DBM induced endochondral bone differentiation both in athymic rats and baboons. Bovine osteogenin in conjunction with baboon insoluble collagenous matrix induced extensive bone differentiation in athymic rats and baboons. Baboon and human DBM did not induce bone differentiation in euthymic rats and, in athymic mice, baboon DBM failed to induce bone differentiation, determining instead the recruitment of multinucleated giant cells. The results indicate that in rodents bone differentiation induced by intact bone matrix is species specific and that T-cell functions are not a requirement for bone induction, although immunologically competent rats block bone differentiation from xenogeneic matrix. Bone differentiation induced by human DBM in baboons suggests that intact bone matrices may not be species-specific amongst primates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The morphogenesis of bone in replicas of porous hydroxyapatite obtained from conversion of calcium carbonate exoskeletons of coral.

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.

Animals↗
PubMed1991

Bone induction in nonhuman primates. An experimental study on the baboon.

Development leading to local bone differentiation in response to intramuscular and subcutaneous implantation of demineralized bone matrix has been predominantly investigated in rodents. To investigate bone differentiation by induction in primates, diaphyseal bone was harvested from ten male baboons and chemosterilized to obtain autolyzed, antigen-extracted allogeneic (AAA) bone containing the bone morphogenetic protein essential for osteoinduction. A total of 96 AAA bone diaphyseal cylinders were implanted intramuscularly in 24 adult male baboons and harvested at three, six, and nine months. Histologic analysis showed that the matrix had undergone considerable resorption, particularly at six and nine months. Seventy-three implants showed variable amounts of newly formed bone at the internal and external surfaces of the chemosterilized matrix. Numerous specimens showed florid bone formation, and newly formed woven bone persisted in association with the matrix for as long as nine months. Coating the AAA bone matrix with an allogeneic fibrin-fibronectin protein concentrate prepared from fresh-frozen baboon plasma did not significantly increase the amount of induced bone. Bone formation was confirmed by intravital double tetracycline labeling of the mineralization fronts. The unequivocal demonstration of bone formation by induction in a large series of adult nonhuman primates provides evidence that long-lived higher vertebrates retain the bone-inductive proteins in the extracellular matrix of bone and the crucial set of responding mesenchymal cells capable of transformation and differentiation into osteoblastic cell lines.

Animals↗
PubMed1990

Multiple myeloma of the periodontium. A case report.

Multiple periodontal lesions were the presenting features leading to a diagnosis of multiple myeloma in a 38-year-old male. Ulceration and bleeding from a rapidly growing retromolar myelomatous mass, multiple foci of alveolar bone destruction and cortical expansion together with multifocal skeletal destruction were the hallmarks of the neoplastic process. Radiotherapy and chemotherapy brought a substantial, but temporary, remission with improvement of the periodontal condition. A sudden exacerbation of the died 22 months after the diagnosis was made.

Adult↗
PubMed1989

Bone induction in a composite allogeneic bone/alloplastic implant.

This study evaluated the morphogenetic properties of the bone matrix as a biological delivery system in a composite allogeneic bone/alloplastic implant placed in extraskeletal recipient sites in rats. Seventy-two allogeneic diaphyseal bone cylinders were chemosterilized to obtain autolyzed antigen-extracted allogeneic (AAA) bone and implanted in twenty 140- to 160-day-old rats. In 30 implants, porous hydroxyapatite biomatrix (HAB) was inserted into the AAA bone cylinders creating the composite implants. Serial sections from the specimens harvested at 23, 30, 45, 53, and 63 days showed that 84% of the AAA bone cylinders induced the differentiation of variable amounts of endochondral bone and that in 61% bone formed in the interior of the cylinders; 74% of the composite implants had no bone-inductive effect, recruiting instead macrophages and multinucleated giant cells at the HAB/mesenchymal interface. In all instances bone failed to form within the porous HAB or in proximity to the AAA bone matrix facing the interior of the cylinders. When present, bone formed only in localized areas within the matrix. Histologic analysis showed that high deposits of induced bone are correlated to high levels of matrix vascular invasion and mesenchymal cell aggregation. Within the limits of this study on rodents, the results suggest that the HAB inhibits and delays the local differentiation of induced bone in the composite implants.

Animals↗
PubMed1989

Patterns of healing on replanted baboon incisors coated with an allogeneic fibrin-fibronectin protein concentrate.

This study investigated the use of an allogeneic fibrin-fibronectin protein concentrate (AFFP) in preventing ankylosis and root resorption on replanted teeth during healing. In 2 adult male baboons (Papio ursinus) after extraction of the mandibular incisors, the coronal two-thirds of the exposed roots were planed to remove the remnant of the periodontal ligament and the cementum. The exposed dentinal surfaces were demineralized with citric acid at pH 1 for 3 min and notched at the junction between the planed and non-planed surfaces. Before replantation, the experimental roots and alveoli were coated with the AFFP prepared from pooled fresh-frozen baboon plasma. The animals were killed 55 days after operation and histometrical analysis was performed on serial sections cut in the buccolingual direction parallel to the long axis of the recovered specimens. An analysis of variance demonstrated significant differences between the two treatments with regard to the magnitude of ankylosis (greater for citric acid-demineralized plus AFFP-treated surfaces). There were variations in the magnitude of the different patterns of healing both between and within the experimental and control surfaces. Within the limits of the study, in this primate replantation model, the biochemical treatment of surgically exposed and demineralized root surfaces with AFFP did not enhance connective tissue attachment regeneration nor prevent dentoalveolar ankylosis and root resorption.

Alveolar Process↗
PubMed1989

The hard evidence of alveolar bone loss in early hominids of southern Africa. A short communication.

Since the discovery at Taung of the first early hominid specimen to be recovered in Africa, designated as Australopithecus africanus, the South African Pliocene and earliest Pleistocene deposits of the Blaauwbank Valley (Sterkfontein, Swartkrans, Kromdraai) in the Transvaal and of Makapansgat in the northern Transvaal, have yielded the most spectacular fossilized hominid remains of the genus Australopithecus and associated fauna, together with some intriguing and fascinating specimens of the genus Homo.

Animals↗
PubMed1988

Paleopathology in Australopithecus africanus: a suggested case of a 3-million-year-old prepubertal periodontitis.

The fossil remains of a juvenile Australopithecus africanus specimen from Sterkfontein Member 4 temporally confined on faunal grounds to 2.5-3.0 million years before the present (Myr B.P.) show pathological alterations of the periodontal alveolar process consistent with a case of prepubertal periodontitis. This diagnosis is based on macroscopic features of alveolar bone loss distribution, pattern of periodontal bone destruction, migration of the affected deciduous molars, and on stereomicroscopic and scanning electron microscopic evidence of alveolar bone destruction. Differential diagnoses and pathological exclusions are discussed in terms of localized patterns of periodontal bone destruction and presumptive survival rate. The reported case appears to be the first detailed description of a recognized disease in early hominid evolution.

Africa↗
PubMed1986

Chronic osteomyelitis of the jaws.

The incidence of osteomyelitis has been greatly reduced since the advent of antibiotics. In many 3rd World countries, however, numerous cases of severe advanced osteomyelitis still present annually. A case of subacute osteomyelitis is reported and the pathology and clinical features of chronic osteomyelitis are reviewed.

Adult↗
PubMed1986

Progressive changes of Kaposi's sarcoma of the gingiva and palate. Case report in an AIDS patient.

As the incidence of acquired immunodeficiency syndrome (AIDS) cases is rapidly increasing, it is expected that the oral lesions of Kaposi's sarcoma (KS) related to AIDS will be encountered more frequently. The progressive changes of KS of the gingiva and palate are described in an AIDS patient who has been monitored for 7 months. In the initial stage, the oral manifestations of KS can be confused with various other lesions. The histopathological appearance includes proliferating slit-like vascular channels and scattered macrophages containing numerous hyaline, eosinophilic granules. Rapid neoplastic proliferation seems to be related to cyclical episodes of impaired immunity.

Acquired Immunodeficiency Syndrome↗