A histologic assessment of a HYBENX® oral tissue decontaminant in vital pulp therapy in dogs.

The aim of this study was to assess HYBENX® Oral Tissue Decontaminant (HOTD) in treating vital pulp exposure in a canine model. The use of HOTD solution was compared to an accepted and standard regimen for vital pulp exposure, an application of a commercial calcium hydroxide product (Ca(OH)2). Both control and experimental treatments were followed by restoration with a commercial zinc oxide and eugenol obtundant intermediate restorative material and thermal insulator (ZOE). At 7 days there was 100% pulp vitality with HOTD and 50% with Ca(OH)2. New dentin formation was seen in 62.5% of the HOTD treated pulps and none of the Ca(OH)2 treatment group. The vital pulp exposures at day 21 post treatment with HOTD also showed significant improvement over Ca(OH)2 in the presence of odontoblasts, new dentin formation and pulp survivability. The presence of odontoblasts and new dentin was noted in 71% of the HOTD cases versus 50% of the survivable Ca(OH)2 cases. Furthermore, 100% of HOTD cases had vital pulps versus 62.5% of Ca(OH)2 cases. The 60-day specimens of both experimental and control techniques exhibited histologically similar appearances and were similar in outcomes. HOTD treatment at day 7 showed a significant positive difference, both in the formation of new dentin and tooth vitality. HOTD proved better for the post 21-day specimens and equivalent for the 60-day pulp specimens with no evidence of untoward tissue reactions or results.

A comparison of screening methods in two early phase oral leukoplakia clinical trials.

OBJECTIVES/INTRODUCTION: Clinical trial accrual for oral dysplasia is difficult in the United States and elsewhere. Patients with dysplastic oral leukoplakia progress to frank invasive carcinoma at a rate of 5-37% over 5 years. We compared two clinical trial screening efforts to hopefully devise better accrual strategies to these types of clinical trials. METHODS: For the first trial, we identified 244 patients with dysplastic oral leukoplakia in our university database and a media campaign. Patients were notified and screened by examination and biopsy. For the second clinical trial, we established a preneoplastic lesions clinic and teaching and communications network with regional oral healthcare professionals. RESULTS: Only one of 244 patients accrued to the first clinical trial through an organized screening effort based on database/medical records review. The second clinical trial accrued 16/30 screened patients through redirected efforts in teaching, communications, and a preneoplastic lesions clinic. CONCLUSION: We conclude that significant difficulties resulted from medical record/database review of leukoplakia patients as a screening method for leukoplakia clinical trial entry. We feel that persistent direct contact and education of healthcare professionals who are likely to examine leukoplakia patients improved accrual to the second clinical trial.

Effects of implant healing time on crestal bone loss of a controlled-load dental implant.

The universally accepted concept of delay-loaded dental implants has recently been challenged. This study hypothesizes that early loading (decreased implant healing time) leads to increased bone formation and decreased crestal bone loss. We used 17 minipigs to study implants under a controlled load, with non-loaded implants for comparison. Radiographic and histological assessments were made of the osseointegrated bone changes for 3 healing times (between implant insertion and loading), following 5 months of loading. The effect of loading on crestal bone loss depended on the healing time. Early loading preserved the most crestal bone. Delayed loading had significantly more crestal bone loss compared with the non-loaded controls (2.4 mm vs. 0.64 mm; P < 0.05). The histological assessment and biomechanical analyses of the healing bone suggested that loading and bioactivities of osteoblasts exert a synergistic effect on osseointegration that is likely to support the hypothesis that early loading produces more favorable osseointegration.

An assessment of root cementum in cleidocranial dysplasia.

The purpose of this prospective study was to determine if there is a difference between the amount of cellular and acellular cementum on the roots of 2 teeth extracted from a subject with cleidocranial dysplasia (CCD) compared to 10 teeth extracted from 10 subjects unaffected by CCD. The cementum of 2 permanent teeth, which had been extracted from the CCD subject, was examined and histomorphometrically analyzed for comparison to the cementum of 10 anterior teeth that had been extracted from individuals who were unaffected by CCD. The percentage of the root covered by cellular or acellular cementum was quantified to determine if patients affected by CCD typically lack cellular cementum. In the roots of the 2 permanent teeth of the subject with CCD, a mean of 18.05 +/- 10.67% was covered by cellular cementum and 76.90 +/- 3.53% was covered by acellular cementum. In the 10 permanent teeth from subjects without CCD, a mean of 19.12 +/- 15.60% of the root was covered by cellular cementum and 80.34 +/- 15.71% was covered by acellular cementum. The findings indicate that there is no statistically significant difference between the amount of either cellular or acellular cementum covering the roots of the study subject with CCD and the roots of the 10 control teeth. The presumption that a lack of cellular cementum causes the increased number of unerupted teeth in patients with CCD is not supported by the findings of this study.

Histologic evaluation of hydroxyapatite-coated root-form implant retrieved after 7 years in function: a case report.

This case report presents a clinical, radiographic, and histologic evaluation of 2 non-adjacent, hydroxyapatite-coated, root-form implants retrieved from the maxillary canine area of a patient after 7 years in function. Clinical examination revealed immobile implants with no sign of pathosis. Radiographic examination indicated close proximity of the bone to the implant surface without evidence of radiolucency. Histologically, the 2 implants appeared to be well integrated with the surrounding bone; 84% of the surface of the first implant and 79% of the surface of the second implant had close bone apposition at the interface. There was no evidence of dissolution of the hydroxyapatite coating. The bone appeared to be in immediate contact with the coating. These observations suggest that a particular hydroxyapatite coating on root-form implants can resist degradation during long-term function.

Frequency of stromal lineage colony forming units in bone marrow of peroxisome proliferator-activated receptor-alpha-null mice.

The bone marrow stroma, consisting of adipocytes, fibroblasts, and osteoblasts, develops from a multipotent mesenchymal progenitor. The recently described nuclear hormone receptors, known as peroxisome proliferator-activated receptors (PPARs), regulate transcription of genes involved in adipogenesis. Consistent with this is the observation that PPARalpha-null mice exhibit greater extramedullary adipose stores compared with their wild-type controls. To determine if the status of the PPARalpha protein also influenced bone marrow stromal cell differentiation, this study compared the frequency of colony forming units for bone marrow adipocytes (CFU-A), alkaline phosphatase-positive fibroblasts (CFU-F/ALP+), and osteoblasts (CFU-O) between wild-type and PPARalpha-null mice. The CFU frequencies for all lineages were not significantly different in either gender at age 3 weeks, independent of the PPARalpha background. However, histologic analysis showed that the cross-sectional area of the femur in male PPARalpha null mice was significantly greater than that of PPARalpha-null female mice and of both wild-type genders. This was due to an increased marrow cavity space rather than an increased cortical bone area. In addition, while the percentage area of cortical bone occupied by lacunae was equivalent in the PPARalpha and wild-type males, this value was significantly greater in PPARalpha-null female mice compared with wild-type females. At age 3-6 months, no significant difference was observed in the CFU-A frequencies, based on either PPARalpha status or gender. The wild-type male CFU-F/ALP+ frequency was significantly greater than the CFU-F/ALP+ in all other groups. Although the PPARalpha status had no influence on the CFU-O frequency, the number of CFU-O was greater in male than in female mice. Sequential incubation of stromal cells in either adipogenic- or osteoblastic-inducing media did not alter the number of CFU-A or CFU-O. These results indicate that the PPARalpha-null genotype does not influence bone marrow stromal cell numbers.

Histologic and clinical comparison of bilateral sinus floor elevations with and without barrier membrane placement in 12 patients: Part 3 of an ongoing prospective study.

In 1993 the Department of Implant Dentistry at New York University College of Dentistry began a long-term clinical, histologic, histomorphometric, and radiographic study of the sinus elevation procedure. One of the parameters under evaluation in this study is the effect of barrier membrane placement on the creation of vital bone in the grafted sinus cavity. This report presents a histologic and histomorphometric evaluation of healing with and without the placement of an expanded polytetrafluoroethylene (e-PTFE) barrier membrane over the lateral window at the time of sinus grafting. The data were collected from 12 patients who underwent bilateral sinus elevation surgery. In each of these 12 patients the same grafting material was used in both sinuses, making the presence or absence of an e-PTFE barrier membrane the only controlled variable. Under the conditions of this study, the results indicate that (1) placement of the barrier membrane tends to increase vital bone formation; (2) placement of a barrier membrane has a positive effect on implant survival; and (3) membrane placement should be considered for all sinus elevation procedures.

Tendon-to-bone healing of a semitendinosus tendon autograft used for ACL reconstruction in a sheep model.

Anterior cruciate ligament (ACL) reconstruction was performed in a single hind limb of 30 sheep using a doubled semitendinosus tendon graft. Three additional animals were used as controls. Histologic and biomechanical analysis was performed from 4-52 weeks postoperatively. Perpendicular collagen fibers were found connecting the tendon graft to the bone tunnels at 8 weeks. These fibers were seen circumferentially at 12 weeks. By 24 weeks, the bone tunnel was well-defined, and no further changes were observed at 52 weeks. Tendon incorporation within the femoral and tibial tunnels was similar at each interval. Although the small sample size did not permit statistical testing, the reconstruction strength was similar up to 12 weeks (15%-19% of controls). This increased at 24 (28%) and 52 (40%) weeks. The stiffness primarily increased from 4-8 weeks (18%-39%) and 24-52 weeks (52%-82%). Up to 12 weeks, failures occurred by graft pull-out from the bone tunnel. All 24- and 52-week specimens ruptured through the intra-articular portion of the graft, further indicating sufficient graft incorporation within the bone tunnels.

Human histologic and histomorphometric analysis comparing OsteoGraf/N with PepGen P-15 in the maxillary sinus elevation procedure: a case report.

The use of the anorganic bovine bone mineral OsteoGraf/N combined with demineralized freeze-dried bone allograft has received widespread use in sinus elevations. This composite graft material has proven to be suitable, predictable, and successful for the placement and integration of endosseous implants in the edentulous, atrophic maxilla. In this case study, the current materials and accepted methodology were compared with the latest tissue-engineered bone replacement graft material, PepGen P-15. PepGen P-15 is a combination of OsteoGraf/N and a synthetic peptide (P-15) that mimics the cell-binding domain of Type-I collagen responsible for cell migration, differentiation, and proliferation. The radiographic, histologic, and histomorphometric evaluations of the sinus grafted with PepGen P-15 showed enhanced bone formation within a shorter time interval compared with the composite graft material of OsteoGraf/N and demineralized freeze-dried bone allograft.

Postmortem histologic evaluation of mandibular titanium and maxillary hydroxyapatite-coated implants from 1 patient.

Postmortem examination of human specimens is an extremely important aspect of evaluating the relative compatibility and long-term success of endosseous implant surfaces. The bone-implant interface of 5 commercially pure titanium screw-type mandibular implants after 85 months of service and 2 hydroxyapatite- (HA) coated maxillary implants after 38 months of service were examined. All implants were stable at the time of the patient's death. The mandibular implants had an average of 65% contact with bone and the maxillary implants had an average of 47% contact. The HA coating had separated from the maxillary implants in some areas and was free within surrounding connective tissue or surrounded by invaginating sulcular epithelium. The arrangement and pattern of bone contact appeared different between HA-coated and titanium implant surfaces.

Evaluation of titanium implants placed into simulated extraction sockets: a study in dogs.

The purpose of this study was to evaluate the effect of gap width on bone healing around implants placed into simulated extraction socket defects of varying widths in 10 mongrel dogs. All premolars were removed and the alveolar ridges were reduced to a width of 7 mm. Nine weeks later, a total of 80 implants, 10 mm long by 3.3 mm wide, were placed into osteotomy sites prepared to 3 different diameters in the coronal half, simulating extraction sockets. Three experimental sites, with gap sizes of 0.5 mm, 1.0 mm, and 1.4 mm, were created; the control sites had no gap. The depth of each defect was measured at the time of implant placement. All implants were stable at the time of placement. The dogs were euthanized 12 weeks after implant placement, and blocks containing the implants and adjacent bone were submitted for histologic evaluation. Clinically, all control and test sites healed, with complete bone fill in the defect. Percentages of bone-to-implant contact were measured histologically. As the gap widened, the amount of bone-to-implant contact decreased, and the point of the highest bone-to-implant contact shifted apically. These changes were statistically significant (P < .001). No statistically significant differences in bone-to-implant contact were found between the sites when the apical 4 mm of implants were compared. Within the limits of this study, the simulated extraction socket defects healed clinically, with complete bone fill, regardless of the initial gap size. However, the width of the gap at the time of implant placement had a significant impact on the histologic percentage and the height of bone-to-implant contact.

Sinus floor elevation using anorganic bovine bone matrix (OsteoGraf/N) with and without autogenous bone: a clinical, histologic, radiographic, and histomorphometric analysis--Part 2 of an ongoing prospective study.

One of the goals of the sinus elevation procedure is the creation of vital bone to effect the osseointegration of dental implants placed in the posterior maxilla. With this goal in mind, in 1993 the Department of Implant Dentistry at New York University College of Dentistry began a long-term clinical, histologic, histomorphometric, and radiographic study of the sinus elevation procedure. The primary parameters included the effects of graft material selection, time allowed for graft maturation, and the effect of barrier membrane placement on the creation of vital bone in the sinus cavity. The effects of these and other parameters on implant survival rates were also to be evaluated. This paper reports the data collected on a subgroup of 113 sinus elevations that used anorganic bovine bone matrix (OsteoGraf/N) alone or in combination with autogenous bone and/or demineralized freeze-dried bone as a graft material. This is the second in a proposed series of papers that will result from this ongoing research project. The results of this study indicate that: OsteoGraf/N appears to be an effective graft material with a 98.2% implant survival rate to date: vital bone formation increased with time; vital bone formation increased moderately when demineralized freeze-dried bone allograft was added, and increased substantially when intraoral autogenous bone was added or when an expanded polytetrafluoroethylene membrane was used; and the increased height achieved by the procedure was stable over a 3-year period. Because of the high overall implant survival rate, it was not possible to determine the relationship between vital bone formation or membrane usage and implant survival.

Bone formation and reosseointegration in peri-implantitis defects following surgical implantation of rhBMP-2.

This study was designed to evaluate bone formation and reosseointegration following surgical implantation of recombinant human bone morphogenetic protein-2 (rhBMP-2) in peri-implantitis defects. Hydroxyapatite-coated dental implants were placed bilaterally in the mandibular and maxillary premolar area in four rhesus monkeys and were allowed to osseointegrate for 1 year. Cotton ligatures were then placed around the healing abutments, and plaque was allowed to accumulate for 11 months. Resulting circumferential peri-implantitis defects exhibited a large intrabony and horizontal component. At reconstructive surgery, peri-implantitis defects in contralateral jaw quadrants were randomly assigned to receive rhBMP-2 (0.43 mg/mL implant volume) in an absorbable collagen sponge carrier or a carrier control. The animals were sacrificed 4 months postsurgery, and block sections were prepared for histometric analysis. Summary statistics included means calculated per animal. Paired t tests were used to evaluate differences between experimental conditions (n = 4). Defect depth amounted to 3.4 +/- 0.9 mm and 3.2 +/- 0.9 mm for rhBMP-2 and control defects, respectively. Vertical bone gain in rhBMP-2 defects (2.6 +/- 1.2 mm) was significantly greater than in controls (0.8 +/- 0.8 mm; P < .01). Reosseointegration within the confines of the defect for rhBMP-2 defects (29.0 +/- 10.5%) differed significantly from that in the control (3.5 +/- 2.5%; P < .01). Reosseointegration within the extent of newly formed bone averaged 40.0 +/- 11.0% in rhBMP-2 defects as compared to 8.9 +/- 7.8% in the control (P < .01). Osseointegration in resident bone amounted to 69.5 +/- 6.9% and 72.6 +/- 8.0% for rhBMP-2 and control defects, respectively. There is significant evidence that rhBMP-2 has potential to promote bone formation and reosseointegration in advanced peri-implantitis defects in a demanding nonhuman primate model.

Effect of allogeneic, freeze-dried, demineralized bone matrix on guided bone regeneration in supra-alveolar peri-implant defects in dogs.

This randomized, split-mouth design study evaluated the adjunctive effect of allogeneic, freeze-dried, demineralized bone matrix on guided bone regeneration in a critical-size, supra-alveolar, peri-implant defect model. Contralateral supra-alveolar peri-implant defects, 5 mm in height, each including two titanium implants, were surgically created in five beagle dogs. Demineralized bone matrix in autologous blood was placed over the implants in one randomly selected mandibular jaw quadrant. A space-making expanded-polytetrafluoroethylene membrane was used to provide guided bone regeneration bilaterally. Following a 16-week healing interval, tissue blocks were harvested and prepared for histometric analysis. Differences between experimental conditions (guided bone regeneration sites with and without demineralized bone) were evaluated using paired t tests (n = 4). Demineralized bone particles were discernible, with limited signs of resorption. The bone matrix particles appeared to be solidified within a dense connective tissue matrix and in close contact with the implants. Limited matrix remineralization was apparent adjacent to the alveolar crest. No statistically significant differences were found between experimental conditions for any parameter examined. Peri-implant defect height averaged 5.0 +/- 0.2 mm and 4.9 +/- 0.4 mm, vertical bone regeneration 1.5 +/- 0.9 mm and 1.1 +/- 0.4 mm, osseointegration within the extent of the defect 10.0 +/- 3.9% and 15.3 +/- 5.3%, osseointegration within the extent of regenerated bone 30.4 +/- 13.7% and 52.1 +/- 17.9%, and osseointegration within the alveolar base 68.8 +/- 13.1% and 74.4 +/- 7.1% for guided bone sites with and without demineralized bone, respectively (P > .05). The results suggest that freeze-dried demineralized bone has no adjunctive effect on guided bone regeneration in supra-alveolar peri-implant defects, that guided bone regeneration has a limited potential to enhance alveolar regeneration in this defect model, and that a 16-week healing interval appears insufficient for turnover and maturation of demineralized bone under provisions for guided bone regeneration.

Oral mucosal melanomas: the WESTOP Banff workshop proceedings. Western Society of Teachers of Oral Pathology.

A workshop to discuss primary oral melanomas was convened at the annual Western Society of Teachers of Oral Pathology meeting in Bannf, Alberta, Canada. Fifty oral melanomas, identified from the files of the participants, were reviewed in order to better understand the clinical features, histologic spectrum, and natural history of these perplexing lesions. Results confirmed that oral melanomas occur in adults almost three times more frequently in men than women and have a decided predilection for the palate and gingiva. Some lesions exhibit a clinically detectable and prolonged in situ growth phase, whereas others seem to lack this property and exhibit only or predominantly invasive characteristics. Recurrences, metastases, and death from tumor were characteristic of the follow-up of a limited number of patients. Until definitive prospective data are collected that elucidate natural history, oral mucosal melanomas should be tracked separately from cutaneous lesions. All oral pigmented lesions that are not clinically diagnostic should be biopsied. Lesions with equivocal histopathologic features might be referred to as "atypical melanocytic proliferation" and should be excised. Recognition of lesions in an early in situ phase and aggressive treatment should have a favorable effect on prognosis. To enhance future or prospective study of these rare neoplasms, guidelines for reporting oral melanomas are suggested.

Postmortem histologic evaluation of hydroxyapatite-coated cylinder and titanium alloy basket implants in situ for 37 months in the posterior mandible. Dental Implant Clinical Research Group.

Histologic examination of the tissues surrounding a titanium alloy basket implant and a hydroxyapatite-coated titanium cylinder implant from the mandible of a cadaver were examined. The 67-year-old man died 37 months after first-stage surgery from cardiovascular failure. Clinical and radiographic examinations indicated that the implants were functional, immobile, and integrated. Light microscopy revealed that the gingival tissues adjacent to the implants were healthy and, in general, free of inflammatory cells. The transmucosal area demonstrated a tight connective tissue apposition to the implants. The sulcular epithelial appearance was similar to that of a natural tooth. Histomorphometric analysis revealed that 72.2 percent of the basket implant and 75.3 percent of the hydroxyapatite-coated implant were in direct contact with bone. Generally, the bone along the surface of the basket implant was thicker than the bone along the surface of the hydroxyapatite-coated cylinder. Bone grew through the vent hole areas of both implants.

Bone morphogenetic protein-2 for peri-implant bone regeneration and osseointegration.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) induced bone regeneration and osseointegration was evaluated in supraalveolar peri-implant defects in 5 beagle dogs. Alveolar bone was reduced 5 mm in height in mandibular premolar areas and the premolars were extracted. Three 10 mm titanium fixtures were placed 5 mm into each reduced alveolar crest, leaving 5 mm in a supraalveolar position. Alternate quadrants in consecutive animals received a surgical implant consisting of 2 ml rhBMP-2 (0.43 mg/ml) in a type I bovine collagen carrier, or the carrier alone (control). Fixtures and surgical implants were submerged under the gingival flaps. The healing interval was 16 weeks. Histometric and radiographic evaluations were made. Defect height averaged (+/- SD) 5.3 +/- 0.2 and 5.1 +/- 0.2 mm for rhBMP-2 and control defects, respectively (P > 0.05, n = 5, paired, t-test) Bone regeneration (height) averaged 4.2 +/- 1.0 and 0.5 +/- 0.3 mm for rhBMP-2 and control defects, respectively (P < 0.05). Bone regeneration (area) averaged 6.1 +/- 6.3 and 0.2 +/- 0.2 mm2 for rhBMP-2 and control defects, respectively (P > 0.05). Osseointegration within the confines of the defect averaged 19.1 +/- 10.1% and 8.2 +/- 4.6% for rhBMP-2 and control defects, respectively (P > 0.05). Osseointegration within regenerated bone averaged 29.1 +/- 9.8% and 65.3 +/- 15.3% for rhBMP-2 and control defects, respectively (P < 0.05). Osseointegration within the retained alveolar bone averaged 67.1 +/- 4.6% and 68.1 +/- 3.6% for rhBMP-2 and control defects, respectively (P > 0.05). The results suggest that there is a potential for rhBMP-2 induced bone regeneration and osseointegration in surgical peri-implant defects.

Bone formation and osseointegration stimulated by rhBMP-2 following subantral augmentation procedures in nonhuman primates.

The purpose of this study was to evaluate bone formation and osseointegration using titanium dental implants in the subantral space following surgical implantation of recombinant human bone morphogenetic protein-2 (rhBMP-2). In each of four cynomolgus monkeys, one subantral site was treated with rhBMP-2 (0.19 mg per implant) in an absorbable collagen sponge (ACS). The contralateral site was treated with vehicle in ACS (control). Three months later, two screw-type titanium dental implants were placed into each augmented sinus, and one additional implant was placed immediately anterior to the sinus. Thus, each animal had three experimental sites: rhBMP-2, control, and nonsinus. Animals were sacrificed after an additional 3 months, and block sections were harvested and prepared for histometric analysis. Analysis of variance and t tests were used to evaluate differences between experimental conditions. Mean (+/- SD) vertical bone gain was significantly greater in rhBMP-2 than in control sites (6.0 +/- 0.3 versus 2.6 +/- 0.3 mm; P < .002). Bone density in rhBMP-2 sites averaged 14.4 +/- 2.9% versus 13.9 +/- 4.6% and 14.1 +/- 3.6% for control and nonsinus sites, respectively, without significant differences between experimental conditions. Bone-implant contact in rhBMP-2 sites (41.4 +/- 7.7%) was not significantly different from that in control (38.9 +/- 12.4%) and nonsinus sites (46.8 +/- 10.6%). The present study provides evidence for considerable vertical bone gain in the subantral space following surgical implantation of rhBMP-2, thus allowing placement of dental implants. The newly formed bone appears to be of similar quality and to be as suitable for osseointegration as the residual bone in this nonhuman primate model. Thus, surgical implantation of rhBMP-2 appears to have clinical utility and may provide a realistic alternative to autogenous bone grafts for subantral augmentation procedures.

Tumors of minor salivary glands and the analysis of 106 cases.

This study is based on 106 cases of predominantly minor salivary gland tumors which were received at the University of Oklahoma College of Dentistry Department of Oral Pathology Biopsy Service from 1972 to 1995. (In this study), 55% of the cases were benign and 45% were malignant. Benign tumors include pleomorphic adenoma (68%), monomorphic adenoma (10%), oncocytoma/oncocytosis (7%), papillary cystadenoma (14%), and myoepithelioma (2%). Of the malignant tumors, 34% were mucoepidermoid carcinoma, 17% adenoid cystic carcinoma, 21% adenocarcinoma, not otherwise specified (N.O.S.), 21% polymorphous low-grade adenocarcinoma, and 6% malignant mixed tumors. There was no difference in relative incidence of benign or malignant tumors between males and females. The 7th decade was the peak occurrence age for both benign and malignant and the palate was the most frequent location.