Biomedical subjects

U E Pazzaglia

Publications and source records attributed to U E Pazzaglia.

At least 19 recordsLinked to original sources

PubMed2006

Indications on suitable scaffold as carrier of stem cells in the alveoloplasty of cleft palate.

Autologous iliac crest bone is used to close the residual alveolar bone defect in cleft palate patients during late mixed dentition. Surgery involves physical and anaesthesiologic risks, long-time hospitalization, high costs and not always good results (15% failure rate). Alternatives to iliac crest bone grafting are going to be evaluated: synthetic, xenograft and allograft matrices combined with platelet-rich plasma or recombined bone morphogenic proteins for osteoinductivity are commercially available. These alternatives have not yet been determined to be equivalent to the previous treatment. A new field of research is represented by stem cells, which have been also used to regenerate ischaemic cardiac tissue after heart attack, to treat hypophosphatasia and osteoporosis. Our aim was to use osteoblasts from stem cells to close the residual palate cleft in association with a suitable carrier. Stem cells are expanded in the Aastrom bioreactor, differentiated into osteoblasts and positioned in the bone defect by means of a Spongostan scaffold. This scaffold has the best characteristics as commercial availability, low cost, good manageability, absence of allergic reactions or other side effects on patient, biocompatibility, imbibition, radiotransparency, reabsorbability and osteoinductivity. Previous studies encourage Spongostan scaffold application.

Alveoloplasty↗

PubMed2005

GH-releasing peptides and bone.

It has been extensively demonstrated that GH secretagogues (GHS) play a role in the regulation of bone metabolism in animals and humans. Unlike GH, administration of GHS does not increase bone resorption markers, suggesting that a mechanism exclusively linked to GH release cannot account for the effect of these compounds. On this line, we investigated the effect of GHS and ghrelin, the endogenous ligand of GHS receptors, on bone cells. We found that both hexarelin and ghrelin significantly stimulated cell proliferation and increased alkaline phosphatase and osteocalcin production in primary cultures of rat calvaria osteoblasts. In the same cells, we were able to detect the mRNA for the GHS receptor by RT-PCR and the corresponding protein by Western blot, indicating that ghrelin and GHS may bind and activate this receptor. Two isoforms of GHS receptors (GHS-R), which are presumably the result of alternate processing of pre-mRNA, have been identified and designed receptors 1a (R1a) and 1b (R1b). Ghrelin, the endogenous ligand of the GHS receptors, binds with high affinity GHS-R1a only. Unlike fetal calvaria cells, osteoblasts derived from adult rat tibia did not express the GHS-R1 a, but only the biologically inactive isoform GHS-R1b. The latter isoform was present in only one of the three specimens of human osteoblasts obtained from the iliac crest or the upper femur of patients during surgery. These results would indicate that only osteoblasts from fetal bone express functional receptors responsive to ghrelin and GHS.

Animals↗

PubMed1998

The relevance of hydroxyapatite and spongious titanium coatings in fixation of cementless stems. An experimental comparative study in rat femur employing histological and microangiographic techniques.

Pure titanium rods plasma-spray coated with hydroxyapatite (HA) or porous titanium (Ti) of controlled roughness were implanted bilaterally in the distal femur of Sprague-Dawley rats to compare the extent of bone growth on the two types of coating. The relevance of other factors, like mechanical stability and biological adaptation of the bone to the insertion of a foreign body implant, were investigated in femora which were over-reamed (absence of primary fit) or reamed without insertion of the rod. Continuous tetracycline labeling for the first 30 days and for the last 2 weeks in the 90-day group was performed; histological/histometric, fluorescence and microangiographic studies were carried out on serial sections of the implanted and control femora. In the group of stable implants, HA-coated rods showed 90% integration versus 53% with Ti-coated implants (P < 0.001); in over-reamed implants neither surface bone growth nor endosteal fixation occurred, and both types of rods were surrounded by a thick layer of connective tissue. The study documented early adhesion of osteoblasts and direct deposition of bone matrix on the substrate, while on spongious titanium osteogenesis was observed only in proximity to the surface. Remodeling of the reactive, primary bone to mature, lamellar bone took the form of a capsule surrounding the implants and radial bridges connecting the latter to the endosteal surface. The number, height and thickness of these bridges appeared to be the factors determining implant stability, rather than the extent of the bony capsule on the perimeter of the implant. Integration was a function not only of mechanical conditions and surface geometry, but also of the biological response of the whole bone to changes in the vascularization pattern. The reported phenomena can be seen more easily in experimental models involving small rodents because of their fast bone turnover and revascularization, but it is expected that they take place, even at a lower speed, in clinical situations like cementless stems of total hip replacement.

Angiography↗

PubMed1998

Mutations in the EXT1 and EXT2 genes in hereditary multiple exostoses.

Hereditary multiple exostoses (EXT; MIM 133700) is an autosomal dominant bone disorder characterized by the presence of multiple benign cartilage-capped tumors (exostoses). Besides suffering complications caused by the pressure of these exostoses on the surrounding tissues, EXT patients are at an increased risk for malignant chondrosarcoma, which may develop from an exostosis. EXT is genetically heterogeneous, and three loci have been identified so far: EXT1, on chromosome 8q23-q24; EXT2, on 11p11-p12; and EXT3, on the short arm of chromosome 19. The EXT1 and EXT2 genes were cloned recently, and they were shown to be homologous. We have now analyzed the EXT1 and EXT2 genes, in 26 EXT families originating from nine countries, to identify the underlying disease-causing mutation. Of the 26 families, 10 families had an EXT1 mutation, and 10 had an EXT2 mutation. Twelve of these mutations have never been described before. In addition, we have reviewed all EXT1 and EXT2 mutations reported so far, to determine the nature, frequency, and distribution of mutations that cause EXT. From this analysis, we conclude that mutations in either the EXT1 or the EXT2 gene are responsible for the majority of EXT cases. Most of the mutations in EXT1 and EXT2 cause premature termination of the EXT proteins, whereas missense mutations are rare. The development is thus mainly due to loss of function of the EXT genes, consistent with the hypothesis that the EXT genes have a tumor- suppressor function.

Chromosome Mapping↗

PubMed1998

The effects of bone resorption inhibitors on the growth plate and proximal tibial metaphysis of rats: clinical implications.

This study investigated the effects of diphosphonates at scalar doses in a high bone turnover structure, namely, the proximal tibial metaphysis of rats. Arrest of bone modeling was represented by cylindrical-shaped metaphyses, increased height of the perichondrial bone bark, and persistence of primary metaphyseal trabeculae; these changes were dose-related. Higher doses of the inhibitors produced extension of the growth plate and arrest of the mineralization process. The dose-related dissociation between the effects on bone resorption and mineralization allows the therapeutic use of this class of drugs.

Animals↗

PubMed1998

Morphology of peri-implant regenerated bone, in sheep's tibia, by means of guided tissue regeneration.

BACKGROUND: No data on the resistance to functional loads of bone regenerated by means of guided tissue regeneration, can be found. In this paper the new-formed bone is analyzed, in cases that see the surgical creation of defects in testing animals. The morphological aspects of perimplant bone, regenerated by means of bone substitutes or not, were evaluated. METHODS: A coronal defect was created by means of a counter-sink bur. The following step provided for osseointegrated fixtures, with a machined or blasted (TiOblast) surface, to be installed. Some bone defects were filled with Bio-Oss, and covered with resorbable membrane (Vycril), others were left unfilled. The animals were sacrificed after different periods of time (24 and 45 days). Some thick sections (200 microns) underwent then microradiography and were examined with a microscope, under transmitted and polarized light. Other sections, thin (5 microns), were coloured with toluidine blue, Gomori's Stain and Solochrome Cyanine/Congo red. RESULTS: Data confirm the excellent behaviour of bovine bone and of TiO blasted fixtures. The experimental results bring into evidence that, in cases of Guided Bone Regeneration (GBR) by means of membrane, the use of fixtures with a blasted surface (TiOblast), and of Bio-Oss as bone substitute, made osseointegration easier. CONCLUSIONS: Results, moreover, suggest that in case of implant surgery with GBR, in order to allow the maturation of regenerated bone, it's healing time must be prolonged.

Animals↗

PubMed1997

The reaction to nailing or cementing of the femur in rats. A microangiographic and fluorescence study.

Bone reaction to cement and to a cementless stem was studied in the rat femur with histological fluorescence and microangiographic techniques. Periosteal and endosteal apposition, and consequent remodelling, appeared as a reaction to reaming rather than caused by cement or a cementless stem. Every change in bone began with proliferation, progression and orientation of the vessels. Endosteal apposition was absent in cemented femurs because the entire medulla was occupied by the acrylic cement, but remodelling of the subendosteal cortex followed medullary revascularisation which was far advanced after 90 days. In cementless stems, endosteal apposition of primary woven bone and remodelling was the basis for bony ingrowth and anchorage through bony bridges. Our results suggest that the pattern of blood supply is relevant to the structural organisation of mature lamellar bone around the implant. Cemented stems have maximum anchorage and stability as soon as they are inserted, but this decreases with time as revascularisation occurs. Cementless stems can reach maximum integration later after insertion, and revascularisation is less critical because they usually do not fill the canal completely.

Animals↗

PubMed1997

Pathology of disappearing bone disease: a case report with immunohistochemical study.

A case of disappearing bone disease of the proximal femur is reported with histopathological and immunohistochemical studies. There was a densely packed cellular tissue, positive to endothelial antibodies, in areas of massive bone destruction. A more differentiated vascular tissue was present where trabecular cancellous or cortical bone was preserved with only focal zones of accelerated bone remodelling. The self-limited course correlates well with two phases of evolution of the histopathological lesions with neoplastic-like proliferation of endothelial cells corresponding to the rapid and massive bone destruction, and a later differentiation of the cells in mature vascular structures, but still with accelerated bone resorption which is partly compensated by appositional activity.

Arthroplasty, Replacement, Hip↗

PubMed1997

The effects of mechanical forces on bones and joints. Experimental study on the rat tail.

We have used an experimental model employing the bent tail of rats to investigate the effects of mechanical forces on bones and joints. Mechanical strain could be applied to the bones and joints of the tail without direct surgical exposure or the application of pins and wires. The intervertebral disc showed stretched annular lamellae on the convex side, while the annulus fibrosus on the concave side was pinched between the inner corners of the vertebral epiphysis. In young rats with an active growth plate, a transverse fissure appeared at the level of the hypertrophic cell layer or the primary metaphyseal trabecular zone. Metaphyseal and epiphyseal trabeculae on the compressed side were thicker and more dense than those of the distracted part of the vertebra. In growing animals, morphometric analysis of hemiepiphyseal and hemimetaphyseal areas, and the corresponding trabecular bone density, showed significant differences between the compressed and distracted sides. No differences were observed in adult rats. We found no significant differences in osteoclast number between compressed and distracted sides in either age group. Our results provide quantitative evidence of the working of 'Wolff's law'. The differences in trabecular density are examples of remodelling by osteoclasts and osteoblasts; our finding of no significant difference in osteoclast numbers between the hemiepiphyses in the experimental and control groups suggests that the response of living bone to altered strain is mediated by osteoblasts.

Age Factors↗

PubMed1996

Periosteal and endosteal reaction to reaming and nailing: the possible role of revascularization on the endosteal anchorage of cementless stems.

The reaction of bone to titanium implants of different shapes inserted in the rabbit tibia was investigated with histological and perfusion techniques to determine the pattern of vessel distribution. The experimental implants included full cylindrical rods, hollow rods with holes on the surface and wire mesh rods. In the implanted bones the rods were found to fill a large area of the medullary canal; however, owing to the discrepancy between the shape of the diaphysis and the implant, the endosteal contact was never complete. In an early phase, reactive bone filled the gap between the endosteal and the implant surface; in hollow and wire mesh rods bone had grown inside through the lateral holes or loops of the mesh. Revascularization took place together with remodelling of the endosteal, primary bone to mature lamellar. In full implants a reticle of newly formed vessels developed around the rods; in hollow and wire mesh implants vessels had grown inside the implant itself and the endosteal surface had a more regular profile than in full rods. Wire mesh plugs prevented formation of a peripheral medullary space and showed no encapsulation; wires in contact with or in proximity to the endosteal surface were incorporated by lamellar systems with strong connections with the original cortical bone.

Animals↗

PubMed1994

Histology of the metal-bone interface: interpretation of plastic embedded slides.

The interference of processing and preparation of histological slides for the study of morphology and morphometry of bone-implant interfaces was investigated in an experimental model, in which a titanium plate was inserted through the cortical bone into the medullary cavity of rat tibiae. The thickness of the sections, burr and notching of the cut border, and staining properties of the embedding resin were found to significantly influence the appearance of the bone-implant interface and, when morphometry was applied, the extent of direct bone-metal contact. The model of the interface resulting from this study is that of some bony processes abutting on the metal surface, while most of the contact is between metal and connective tissue or vascular spaces.

Animals↗

PubMed1994

Reversibility of the inhibitory effect of salmon calcitonin on bone resorption in rats.

Inhibition of osteoclastic bone resorption has been induced in growing rats with high doses of salmon calcitonin. This effect was evaluated by measuring the perichondrial ring height of the proximal tibial metaphysis. The aim was to assess whether osteoclastic activity resumed after a period of inhibition with high doses of calcitonin. 20 male Sprague-Dawley rats were treated for 21 days with 100 units/kg/day of salmon calcitonin subcutaneously and killed after 0-60 days, together with non-treated controls at 0 and 60 days. Arrest of metaphyseal modeling and increased height of the perichondrial ring at the end of the period of therapy (P 0.002 versus controls) were observed. Recovery of bone resorption was evident 20 and 40 days after withdrawal of calcitonin.

Animals↗

PubMed1993

Experimental model in vivo for quantitative assessment of bone resorption inhibition.

Quantitative assessment of bone resorption inhibition in vivo is not easily accomplished; methods relying on a count of osteoclasts are questionable, and histomorphometric evaluation of the bone mass presents several technical problems as well. The authors developed a simple method to measure the inhibition of bone resorption by study of the proximal tibial metaphysis of growing rats: the height of the perichondrial bone ring was taken as an index of the balance between osteoblastic and osteoclastic activity because any agent that inhibits osteoclasts (without interference with osteoblasts) produces an increase in the height of this anatomical structure. Since the ring is well demarcated by surrounding tissues, its height can be measured with accuracy and used for quantitative assessment of bone resorption inhibition. This model was tested with salmon calcitonin, and it provides evidence in vivo that this hormone inhibits osteoclastic bone resorption.

Animals↗

PubMed1993

Inhibitory effect of salmon calcitonin on bone resorption: morphological study of the tibial growth plate in rats.

Salmon calcitonin (sCT) at doses of 100 and 50 UI given subcutaneously to growing rats produced in vivo evidence of osteoclastic activity inhibition. Histological assessment was carried out by measuring the perichondrial ring of Lacroix height, and a dose-correlated effect was found. These aspects were coupled with an increase in the osteoclast number and suggested that in studies with bone resorption inhibitors, morphological evaluation based on osteoclasts count is not reliable. The changes of the metaphysis suggested also that sCT affects the activity of hypertrophic chondrocytes of the growth plate. Plasma calcium levels did not differ significantly between treated rats and controls; an increased phosphatemia was observed in sCT-treated animals.

Animals↗

PubMed1993

Chronic intoxication by ethane-1-hydroxy-1,1-diphosphonate (EHDP) in a child with myositis ossificans progressiva.

A child with myositis ossificans progressiva was treated for 8 years with ethane-1-hydroxy-1,1-diphosphonate (EHDP) 30-40 mg/kg per day. Latterly he complained of severe, progressive bone and joint pain which made standing and walking almost impossible. A radiographic skeletal survey showed diffuse ricket-like lesions. Withdrawal of EHDP therapy produced substantial improvement in his general condition as well as in the radiographic appearance of the bones. Multiple exostoses were observed in this case and, particularly those around the knees, presented a peculiar morphology. This supports the theory that exostoses originate from a defect of metaphyseal modelling.

Adolescent↗

PubMed1993

Evaluation of hollow and full stems implanted in the rabbit tibia: preliminary results.

Full and hollow stems were implanted in the right and left tibiae of five rabbits to study the effects of the implant shape on revascularization and remodelling of the bone after 6 months. No significant difference of periosteal and endosteal circumference was observed when the left and right tibiae of each group were compared. Medullary area was, not surprisingly, significantly smaller in the full stem implanted tibiae. The cortical bone area result was significantly higher in the hollow stem group. In hollow stems, vessels were present both inside and outside the implant with connections through the holes of the implant. The observed differences of cortical bone area can be explained in terms of increased vascular spaces inside the cortical bone of full stem implanted tibiae. This supports the hypothesis that hollow implants provide more space for medullary revascularization and are consequently capable of inducing less endosteal remodelling. Cementless prostheses rely for mechanical fixation on a large interface of the implant with bone. Two factors, i.e. revascularization of the medullary canal and stiffness of the stem, can have a relevant effect on the quality of interface. This non-weight-bearing model suggests the relevance of vascular factors.

Animals↗

PubMed1993

Thermal behaviour of hydroxyapatite intended for medical applications.

Four commercial hydroxyapatites (both natural and synthetic) were tested to assess transformations of the chemical and crystalline structure following variation of temperature from 20 to 1600 degrees C. The thermal behaviour of hydroxyapatite is relevant for biomedical applications such as plasma spraying of metallic implants. Thermogravimetric analysis showed a weight loss from each hydroxyapatite specimen, due to a release of structural H2O molecules; all the specimens up to 1300 degrees C were made of crystalline hydroxyapatite, determined by X-ray diffraction; at 1470 degrees C they were made of both hydroxyapatite and calcium phosphate, but at 1570 degrees C of calcium phosphate exclusively. The diffractograms of the hydroxyapatite coatings showed the same peaks as the original powders, so at the chosen plasma-spray procedure level no new phases were formed. The peak height was nevertheless lower in the plasma-sprayed hydroxyapatites for all interplanar spacing values, which indicated a lower degree of crystallinity, associated with a random structure derived from an alteration to the original crystalline network.

Hydroxyapatites↗

PubMed1992

Treatment of slipped capital femoral epiphysis: evaluation of the results of extracapsular epiphysiodesis and open reduction-epiphysiodesis.

The authors review 26 patients who underwent either "in situ" extracapsular epiphysiodesis or intracapsular reduction followed by epiphysiodesis for slipped capital femoral epiphysis (SCFE). A total of 32 operations were performed. In the first group (chronic grade II SCFE), no complications occurred in the 16 operations and the results were excellent in all cases. In the second group (chronic grade II and III SCFE and acute-on-chronic SCFE), in 16 operations we observed four cases of avascular necrosis, two of which accompanied by chondrolysis. Three of these were in cases of acute-on-chronic SCFE. The results confirm that the cases of acute-on-chronic SCFE have the worst prognosis and a much higher risk of avascular necrosis and/or chondrolysis than purely chronic SCFE. Early diagnosis of ischemic complications make it possible to maintain the spherical shape of the femoral head and good joint function. The results are considerably better than in untreated cases.

Adolescent↗