Serafim Papadimitriou

Dentin Regeneration in Vital Pulp Therapy: Design Principales

The nature and specificity of the mechanisms by which the amputated dentin-pulp interface is therapeutically healed determine the properties of the barrier at this site and play a critical role in the outcome of vital pulp therapy. Healing of the dentin-pulp complex proceeds either by natural repair-which results in defensive hard-tissue formation, or therapeutically regulated dentin regeneration, which aims to reconstitute the normal tissue architecture at the pulp periphery. Progress in biomedical research opens new directions for the design of biologically effective pulp therapies. Application of biocompatible and biodegradable carrier vehicles for local delivery of signaling molecules in pulp-capping situations showed induction of fibrodentin/reparative dentin formation, but often at the expense of underlying pulp tissue. An alternative pre-clinical model aiming to reconstitute normal tissue architecture directly at the dentin-pulp interface should be designed on the basis of the direct induction of odontoblast-like cell differentiation and reparative dentin formation at the pulp-capping material interface. Experimental data clearly showed that pulpal cells can differentiate directly into odontoblast-like cells in association with specific extracellular matrices (dentinal or fibrodentinal matrix) or TGFβ1-containing artificial substrates. Dentin-induced dentinogenesis can be used as a master plan for the achievement of new therapeutic opportunities. In the present study, several short-term experimental studies on dog teeth for potential direct induction of odontoblast-like cell differentiation at the surface of rhTGFβ1-containing artificial substrates (Millipore filters, hydroxyapatite granules, calcium hydroxide, pure titanium) failed to induce any specific reparative dentinogenic effects.

Experimental Formation of Dentin-like Structure in the Root Canal Implant Model Using Cryopreserved Swine Dental Pulp Progenitor Cells

OBJECTIVES The purpose of the present study was to present histological and immunohistochemical evidence showing the regenerative capacity of swine dental pulp stem cells (S-DPSCs) seeded on organic or synthetic scaffolds and implanted as hybrid root implants in the jaw bone of minipigs. METHODS Immature permanent incisor teeth and unerupted premolars at the early root-forming stage were extracted from three 7-month-old minipigs, and mesenchymal stem/progenitor cells were isolated from dental pulp. Cells were cryopreserved in liquid nitrogen. A year later, new permanent incisor and premolar teeth were extracted; pulp tissue was removed; and pieces of root canals of the extracted teeth, containing collagen or Poly(lactic-co-glycolic acid) scaffolds seeded with the autologous cryopreserved DPSCs, were implanted into the fresh post-extraction socket of the mini pig jaw. The resulting constructs were harvested after 6 and 10 weeks and evaluated by histological and immunohistochemical analyses. RESULTS Six weeks postoperatively, the central canal space of the root implants showed degrading scaffold material. New extracellular matrix had been deposited in a polar predentin-like pattern on the canal dentinal walls by cuboidal nonpolarized cells. Ten weeks postoperatively, newly formed organic matrix had been consistently deposited on the canal walls. The presence of a continuous layer of polarized cells showing typical columnar morphology adjacent to the newly deposited organic matrix was evident. CONCLUSIONS The interactions of S-DPSCs with the dentin matrix of roots implanted in the jawbone of minipigs constitute a model to study in vivo organization and differentiation potential of DPSCs.

Bone Regeneration Using B-Tricalcium Phosphate in a Calcium Sulfate Matrix

The aim of the study was the histomorphometric comparison of the osteogenic potential of beta-tricalcium phosphate (beta-TCP) alone or in a calcium sulfate matrix. Three round defects, 10 mm (diameter) x 5 mm (depth), were created on each iliac crest of 4 dogs. The defects were divided into 3 groups. Ten defects were filled with beta-TCP in a calcium sulfate (CS) matrix (Fortoss Vital; group A), 10 defects were filled with beta-TCP alone (Fortoss Resorb; group B), and 4 defects were left ungrafted to heal spontaneously (group C). All defects were left to heal for 4 months without the use of a barrier membrane. Histologic evaluation and morphometric analysis of undecalcified slides was performed using the areas of regenerated bone and graft remnants. All sites exhibited uneventful healing. In group A sites (beta-TCP/CS), complete bone formation was observed in all specimens, graft granules dominated the area, and a thin bridge of cortical bone was covering the defect. Group B (beta-TCP) defects were partially filled with new bone, the graft particles still dominated the area, while the outer cortex was not restored. In the ungrafted sites (group C), incomplete new bone formation was observed. The outer dense cortical layer was restored in a lower level, near the base of the defect. The statistical analysis revealed that the mean percentage of new bone regeneration in group A was higher than in group B (49.38% and 40.31%, respectively). A statistically significant difference existed between the 2 groups. The beta-TCP/CS group exhibited significantly higher new bone regeneration according to a marginal probability value (P = .004 < .05). The use of beta-TCP in a CS matrix produced significantly more vital new bone fill and preserved bone dimensions compared with the use of beta-TCP alone.

Dentinogenic responses after direct pulp capping of miniature swine teeth with Biodentine.

INTRODUCTION The aim of this study was to evaluate pulpal responses after experimental direct pulp capping of mechanically exposed teeth with a new calcium silicate-based dentin replacement material. METHODS Thirty-four anterior and posterior teeth of 3 miniature swine were used. Class V or I cavities were prepared on the buccal or occlusal surfaces, respectively. Pulpal exposures were further performed using a round carbide bur 0.8 mm in diameter. Exposures were treated with white MTA Angelus (Angelus, Londrina, PR, Brazil) or Biodentine (Septodont, Saint Maur des Fosses, France), and the cavities were further restored with Biodentine. The pulpal tissue responses were histologically assessed at postoperative periods of 3 and 8 weeks. Data were statistically analyzed using the Kruskal Wallis and the Mann-Whitney U tests. RESULTS Inflammatory infiltration or pulp tissue necrosis was not found in any of the specimens. All teeth showed mineralized matrix formation in the form of a complete hard tissue bridge composed of osteodentin or osteodentin followed by a discontinuous or continuous reparative dentin zone. A significantly higher thickness of the hard tissue bridge was found in the group of teeth treated with Biodentine at both 3 and 8 weeks. A number of teeth, which were under root development at the onset of the experimental procedures, exhibited ectopic pulp calcification. CONCLUSIONS The application of both calcium silicate-based materials in direct contact with the mechanically exposed pulp of healthy miniature swine teeth led to pulp repair with complete hard tissue bridge formation. The thickness of hard tissue bridges was significantly higher after pulp capping with Biodentine.

Transdentinal stimulation of tertiary dentine formation and intratubular mineralization by growth factors.

AIM To evaluate the effects of recombinant growth factors on tertiary dentine formation and intratubular mineralization after their application on deep dentinal cavities in dogs teeth. METHODOLOGY Treatment included dentinal etching (37% phosphoric acid) and applications of bioactive molecules (1 microg mL(-1) TGF-beta1, 10 microg mL(-1) IGF-1, 10 microg mL(-1) bFGF, 10 microg mL(-1) OP-1 or 1 microg mL(-1) monoclonal anti-human TGF-beta1 in phosphate buffered saline, PBS) at the dentinal base of buccal Class V cavities. Control groups were treated with 0.1% dog serum albumin (DSA) in PBS omitting the growth factors. This was performed both with and without dentinal etching. The dentinal responses regarding tertiary dentine formation and intratubular mineralization were assessed after 3 and 8 weeks, respectively, using light and scanning electron microscopy. Some specimens were also subjected to dentine permeability testing. RESULTS The group treated with transforming growth factor-beta1 (TGF-beta1) and, to a lesser extent, the one treated with osteogenic protein-1 (OP-1) showed significantly greater (P < 0.05) tertiary dentine formation and intratubular mineralization over an 8-week period when compared with the control and the other experimental groups. There were no significant differences between groups in reduction in dentine permeability after treatment. CONCLUSION Treatment of exposed dentinal tubules with biologically active molecules might induce intratubular mineralization and tertiary dentine formation. Further research is needed to substantiate any clinical benefits as opposed to traditional treatments of exposed dentine so as to provide a scientific base for the clinical regulation of dentine reactions.

Experimental Dentin-Based Approaches to Tissue Regeneration in Vital Pulp Therapy

The potential direct induction of odontoblastlike cell differentiation at the surface of implanted dentin matrix has been tested in a series of capping experiments. Pieces of Teflon (control) or autogenous dentin matrix were placed in contact with the wound surface at a conventional capping situation, or at the dentinal base of the cavity at a distance from the exposed pulp periphery. Tissue responses were studied by light microscopy after periods of 2 and 4 weeks. Partial degradation of the dentin matrix implants was seen. Formation of atubular calcified matrix, occasionally followed by tubular reparative dentin, was consistently detected in association with dentinal particles. The area between the traumatized dental pulp periphery and the capping material had been occupied by a well-vascularized tissue, regardless of the capping material and postoperative time period. Traces of calcified matrix were detected along the cut dentinal walls. The present data indicate that dentin matrix is limited in its ability to directly induce odontoblastlike cell differentiation and reparative dentin formation at the surface of mechanically exposed pulp of mature teeth. Furthermore, it seems that the traumatized mature pulp maintains the ability to grow, while a calcifying potential could be expressed by this growing part of the pulp core.

Nodular granulomatous glossitis as the sole clinical sign in canine leishmaniosis

A 5.5-year-old, intact male Rottweiler dog was admitted with a history of multifocal nodular tongue lesions which progressively deteriorated during the previous year. Physical examination revealed several reddish nodules with central depression on the surface of the tongue in an otherwise healthy dog. Clinicopathologic abnormalities included eosinophilia and hyperproteinemia. Lingual nodule cytopathology, histopathology, and immunohistochemistry revealed Leishmania spp. amastigotes and a severe granulomatous glossitis. The dog was also seroreactive to L infantum antigens by an indirect immunofluorescence assay. Clinical reevaluation 3 months after the institution of treatment with allopurinol and miltefosine indicated that the nodular lesions had completely regressed. In endemic areas, lingual nodular lesions may rarely be the sole clinical sign of canine leishmaniosis. Standard medical treatment may provide an excellent prognosis.

Influence of a titanium mesh on the management of segmental long bone defects. An experimental study in a canine ulnar model.

OBJECTIVES To evaluate the influence of titanium mesh on guided bone regeneration when used, either alone or in combination with autogenous bone block graft, in a canine ulnar model. METHODS Thirty-two, purpose bred, adult, castrated male Beagles were used, divided into four equal-size groups. A unilateral mid-diaphyseal ulnar critical-size defect was created in each dog. The ulnar segments were stabilized with a stainless-steel plate and screws. Each defect was managed by: no further treatment (Group A) or by placement of a bone block graft taken from the ipsilateral iliac crest (Group B), or titanium mesh wrapped around the ulna (Group C), or a bone block graft and titanium mesh (Group D). After six months, bone block biopsies were performed and the samples were scanned using micro-computed tomography. Qualitative histological evaluation was performed on two non-decalcified longitudinal sections from each block. RESULTS No significant differences in terms of mineralized bone volume were detected between the grafted sites (Groups B and D) or between the non-grafted ones (Groups A and C). The histological evaluation indicated good integration of the bone blocks irrespective of the use of titanium mesh. CLINICAL SIGNIFICANCE The use of titanium mesh does not influence the amount of bone formation. The canine ulnar critical-size defect model seems to be a reliable model to use in experimental studies.

Gingival Hemangiosarcoma of the Left Mandible in a Dog

A ten year old Dogo Argentino cross, was presented with a fast growing mass in the left mandible. The dog underwent hemimandibulectomy and cheiloplasty. No chemotherapeutic regimes were administered, post-operatively. The histopathological findings were suggestive of hemangiosarcoma. The animal survived with no signs of metastasis or recurrence for 5 months, when local recurrence was identified and radiographic examination revealed lung metastasis. Consequently, the owner decided to euthanize the dog. Mandibular hemangiosarcoma is aggressive both locally and systemically as it recurred and metastasized, even after extensive excision. To the authors’ knowledge this is a rare case of mandibular hemangiosarcoma reported in the dog.