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Treatment of intrabony defects with guided tissue regeneration and enamel-matrix-proteins. An experimental study in monkeys.

BACKGROUND: Enamel matrix proteins (EMD) have recently been introduced in regenerative periodontal treatment. However, no histological data are yet available concerning the effect of treating intrabony periodontal defects with EMD, and no histological comparisons have been made comparing the result of treatment of intrabony defects with EMD with that of the treatment with guided tissue regeneration (GTR). AIM: Therefore, the aim of the present study was to evaluate histologically in monkeys the effect of treating intrabony defects with EMD, GTR or combined EMD and GTR. METHOD: Intrabony periodontal defects were produced surgically at the distal aspect of teeth 14, 11, 21, 24, 34, 31, 41 and 44 in 3 monkeys (Macaca fascicularis). In order to prevent spontaneous healing and to enhance plaque accumulation metal strips were placed into the defects. After 6 weeks the defects were exposed using a full-thickness flap procedure. The granulation tissue was removed and the root surfaces were debrided by means of hand instruments. Subsequently, the defects were treated using one of the following therapies: (i) GTR, (ii) EMD, or (iii) combination of EMD and GTR. The control defects were treated with coronally repositioned flaps. After 5 months, the animals were sacrificed and perfused with 10% buffered formalin for fixation. Specimens containing the defects and surrounding tissues were dissected free, decalcified in EDTA and embedded in paraffin. 8 microm thick histological sections were cut and stained and subsequently examined under the light microscope. RESULTS: In the control specimens, the healing was characterized by a long junctional epithelium and limited periodontal regeneration (i.e., new periodontal ligament, new cementum with inserting connective tissue fibers and new bone) in the bottom of the defect. The GTR-treated defects consistently presented periodontal regeneration when the membranes were not exposed whereas the sites treated only with EMD presented regeneration to a varying extent. The combined therapy did not seem to improve the results. CONCLUSION: It can be concluded that all 3 treatment modalities favor periodontal regeneration.

Alveolar Bone Loss↗

Clinical and radiographic findings following application of enamel matrix derivative in the treatment of intrabony defects. A series of case reports.

AIM: The purpose of this case report study was to evaluate the clinical and radiographic findings following application of enamel matrix derivative (EMD) in the treatment of 2- or 3-wall intrabony defects in a private periodontal practice one year after surgery. METHOD: 15 consecutive patients (age range 38 67 years, 9 females, 6 males, 3 smokers) with 25 intrabony defects were included in the study. The decision to use reconstructive surgery was taken at least 3 months after termination of the presurgical treatment phase. Inclusion criteria were: presence of an interproximal area with residual probing depth (PD) > or =6 mm, probing attachment level (PAL) > or =6 mm and an associated intrabony defect > or =4 mm deep and > or =2 mm wide as measured during surgery (defects were not associated with adjacent furcation lesions). Open-flap surgery was performed to expose the defects and the EMD gel was applied after proper debridement. The patients were instructed to rinse 2x daily for 6 weeks with a 0.12% solution of chlorhexidine. RESULTS: At 12 months, mean PD decreased from 8.4 mm to 4.0 mm and PAL from 10.2 mm to 6.6 mm, while recession increased from 1.8 mm to 2.6 mm. Residual PD greater than 4 mm was observed only in 7 sites. 14 sites demonstrated a PAL gain of 2-3 mm, 9 sites a gain of 4-5 mm and 2 sites a gain of 6 mm. Radiographic assessment indicated a mean crestal bone resorption of 20.7% and a mean improvement in the distance between the CEJ and the base of the defect of 22.9%. The combination of defect fill from the bottom of the defect and crestal resorption resulted in a mean defect resolution of 61%. CONCLUSION: Within the limits of this study, the application of EMD gel in 2- or 3-wall intrabony defects resulted in clinically significant gain of PAL and radiographic bone. Further controlled clinical studies are required to confirm the effectiveness of the EMD gel in the treatment of various osseous defects.

Adult↗

Supracrestal soft tissue preservation with enamel matrix proteins in treatment of deep intrabony defects.

BACKGROUND/AIMS: The purpose of the present study was to investigate the effectiveness of a regenerative procedure based on supracrestal soft tissue preservation in association with enamel matrix proteins (EMP) in the treatment of deep intrabony defects. METHODS: The subjects included 35 consecutively treated patients, 23 females and 12 males, aged 28-61 years, 11 of whom were smokers. Patients presented with at least one intrabony defect with probing pocket depth > or = 6 mm and a radiographic depth of the defect > or = 4 mm at the initial visit. Immediately before surgery and 9-12 months after surgery, Local Plaque Score (LPS), Local Bleeding Score (LBS), probing pocket depth (PPD), clinical attachment level (CAL), gingival recession (REC), and radiographic depth of the defect (DEPTH) were recorded. RESULTS: Thirty-one (88.6%) defects were LPS-negative presurgery, while 29 (82.9%) defects presented with no plaque postsurgery. The prevalence of LBS-positive defects shifted from 94.3% presurgery to 8.4% postsurgery (p < 0.0000). PPD was 8.9 mm before surgery, and decreased to 3.5 mm postsurgery (p < 0.0000). CAL varied from 10.1 mm presurgery to 5.4 mm postsurgery (p < 0.0000), with an average improvement (gain) of 4.7 +/- 1.7 mm. Twenty-six (74.3%) defects presented a gain of least 4 mm. Regression analysis showed a positive correlation between CAL gain as a dependent variable, and presurgery PPD and amount of supracrestal soft tissues as predictors. DEPTH improvement (gain) was 3.9 +/- 1.8 mm, which represented 65% of defect fill. Twenty (57.1%) defects presented a DEPTH gain of at least 4 mm. DEPTH gain was significantly correlated to presurgery PPD (p < 0.000). No significant differences were found between smokers and non-smokers in terms of CAL and DEPTH gain. CONCLUSIONS: Results from the present study indicated that the regenerative procedure based on supracrestal soft tissue preservation and EMP application leads to clinically and statistically significant improvement of hard and soft tissue conditions of deep intrabony defects.

Adult↗

Requirement of fibroblast growth factor signaling for regeneration of epiphyseal morphology in rabbit full-thickness defects of articular cartilage.

The involvement of fibroblast growth factor-2 (FGF-2) during the repair process in rabbit full-thickness defects of articular cartilage was studied. Fibroblast growth factor-2 (50 pg/h) was administered for 2 weeks in a 5 mm defect of articular cartilage, which is large enough not to repair spontaneously. The administration of FGF-2 resulted in the regeneration of the articular cartilage and the subchondral bone within 8 weeks. In these defects, undifferentiated mesenchymal cells initiated chondrogenic differentiation coupled with replacement by subchondral bone, resulting in the resurfacing of the defects with hyaline cartilage and the recovery of subchondral bone up to the original bone-articular cartilage junction. In rabbits, full-thickness defects are capable of regenerating articular cartilage as long as the defect size is limited to < or = 3 mm in diameter. In the defects, strong immunoreactivity for FGF-2 was observed in the granulation tissue filling the defects in the early stage of repair, in association with the expression of FGF-2 mRNA shown by in situ hybridization. Once the undifferentiated mesenchymal cells had differentiated into chondrocytes, both the immunoreactivity and the in situ hybridization signal declined significantly. Upon the local administration of a monoclonal antibody against FGF-2 (bFM-1, 50 ng/h), the defects were filled with fibrous tissue and no resurfacing hyaline cartilage was formed. Compared to the non-treated defects, there were marked increases in FGF-2 immunoreactivity and the overexpression of FGF-2 mRNA in the reparative tissue in the bFM-1-treated defects. This rebound phenomenon indicates that the autocrine FGF-2 signaling is critically important for the regeneration of articular cartilage.

3T3 Cells↗

[Absolute filling defects of the optic disc in fluorescein angiograms in glaucoma--a retrospective clinical study].

BACKGROUND: Analysis of clinical importance of the size of filling defects in fluorescein angiograms in primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), ocular hypertension and subjects with physiological excavations in comparison to visual field loss, optic nerve head morphology and hemodynamics. PATIENTS AND METHODS: 75 patients (POAG, NTG, ocular hypertension) and 10 healthy subjects with physiological excavations were included in this study. In digitized video fluorescein angiograms (Scanning Laser Ophthalmoscope) the size of absolute filling defects of the optic disc was quantified in the early venous phase and expressed by percentage of the optic disc. Visual fields were obtained by conventional static perimetry (Humphrey 24-2) and graded in stages of glaucoma visual field defects (Aulhorn I-V). Optic disc excavations were evaluated as cup-to-disc-area-ratios. RESULTS: The filling defects correlated with the visual-field loss stages of Aulhorn and the visual field indices MD (mean deviation), PSD (pattern standard deviation) and CPSD (corrected pattern standard deviation). There was no correlation with the index SF (short-term fluctuation) and with systemic hemodynamics (blood pressure, perfusion pressure) or the IOP. Absolute filling defects correlated with the cup-to-disc-area-ratio in NTG. The absolute filling defects were larger in patients with glaucoma (POAG, NTG) in comparison to patients without glaucomatous visual field loss (ocular hypertension, glaucoma-like discs). No difference of filling defects was found in the glaucoma group (POAG, NTG). Patients with NTG had larger excavations and lower systolic blood pressures than patients with POAG. CONCLUSION: The size of fluorescein filling defects may be useful as a parameter for the evaluation of an ischemic lesion of the optic nerve head. Absolute filling defects may differentiate POAG from ocular hypertension and NTG from glaucoma-like discs without field defects. The results support the hypothesis that in POAG and NTG disturbances of the circulation result in similar filling defects of the optic disc and visual field loss.

Adult↗

Anal sphincter defects in fecal incontinence: correlation between endosonography and surgery.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound provides accurate information about the anatomy of the anal sphincter. The purposes of this study were to evaluate the use of flexible echo endoscopes to examine the anal sphincters, to validate the diagnosis of internal and external sphincter defects obtained using echo endoscopes by comparison with surgical findings, and to assess the outcome after surgical sphincter repair. PATIENTS AND METHODS: Twenty-eight patients (13 women, 15 men, median age 50 years, range 30-83) with fecal incontinence--which was of traumatic origin in all but one (childbirth: n = 8; anorectal surgery: n = 17; biopsy of the prostate: n = 2; no trauma: n =1)--were prospectively investigated by endosonography using an echo colonoscope (n = 14) or an echo gastroscope (n = 14) (CF-UM20, GF-UM20, Olympus Optical). The location and extent of the defects of the internal or external sphincters, or both, were compared with the surgical findings in all patients. The surgical outcome was defined as excellent, improved, or unchanged. RESULTS: At surgery, 25 of the 28 patients had an isolated internal sphincter defect (n = 15) or combined sphincter defect (n = 10). Endoscopic ultrasound identified all of the external anal sphincter defects (n = 10), and correctly excluded a defect in 15 of 18 patients (sensitivity, specificity, and accuracy 100%, 83% and 89%, respectively). All of the internal sphincter defects (n = 25) were detected by endosonography. In three patients, a postulated intact internal sphincter was confirmed by surgery (accuracy 100%). In two patients, the extent of the sphincter defect was underestimated. Despite good visualization of the internal and external anal sphincters, as well as of the puborectal muscle in all patients, the shape, diameter, and full radial image sector (360 degrees) of the echo gastroscope made this instrument more practicable than the echo colonoscope. Nineteen of 25 patients who underwent surgery (76%) with proved sphincter defects experienced improvement, the figure reaching 87% (13 of 15) in patients who received isolated internal sphincter defect repair. CONCLUSIONS: Anal endosonography, even using flexible echo endoscopes, is an accurate method for identifying anal sphincter defects, and is the method of choice for preoperative sphincter mapping with special regard to internal sphincter repair, which can be carried out with excellent results.

Adult↗

Risk of selected birth defects with prenatal illicit drug use, Hawaii, 1986-2002.

The literature on the association between prenatal illicit drug use and birth defects is inconsistent. The objective of this study was to determine the risk of a variety of birth defects with prenatal illicit drug use. Data were derived from an active, population-based adverse pregnancy outcome registry. Cases were all infants and fetuses with any of 54 selected birth defects delivered during 1986-2002. The prenatal methamphetamine, cocaine, or marijuana use rates were calculated for each birth defect and compared to the prenatal use rates among all deliveries. Among all deliveries, the prenatal use rate was 0.52% for methamphetamine, 0.18% for cocaine, and 0.26% for marijuana. Methamphetamine rates were significantly higher than expected for 14 (26%) of the birth defects. Cocaine rates were significantly higher than expected for 13 (24%) of the birth defects. Marijuana rates were significantly higher than expected for 21 (39%) of the birth defects. Increased risk for the three drugs occurred predominantly among birth defects associated with the central nervous system, cardiovascular system, oral clefts, and limbs. There was also increased risk of marijuana use among a variety of birth defects associated with the gastrointestinal system. Prenatal uses of methamphetamine, cocaine, and marijuana are all associated with increased risk of a variety of birth defects. The affected birth defects are primarily associated with particular organ systems.

Adult↗

Occurrence of vertical bone defects in dentally aware individuals.

A vertical (angular) defect is a radiographic diagnostic phenomenon of severe periodontal destruction. The objective of the present study was to investigate the prevalence and severity of vertical defects in a population of dentally aware individuals at 2 different points in time, 1982 and 1992. Intra-oral radiographs of 251 individuals in 1982 and 247 individuals in 1992 in the age range 21-70 years were assessed with regard to presence or absence of vertical defects adjacent to a maximum of 28 teeth per person. A vertical bone defect was defined as a one-sided bone resorption of the interdental marginal bone > or = 2 mm that had a typical angulation towards either the mesial or distal aspect of the root. 'The prevalence of vertical defects in 1982 was 38% increasing from 11% in age 21-30 years to 64% in age 51-70 years, and 27% in 1992 increasing from 7% to 47% in the same age groups, respectively. The number of defects per person increased with age. The majority of affected individuals had 1-2 defects and only about 5% were severely affected. Vertical defects were more common in the posterior as compared to the anterior region of the dentition and the distribution of defects within the maxilla as well as the mandible typically revealed a right-hand to left-hand side symmetry. Vertical defects seem to be a rare phenomenon in dentally aware individuals. In particular, multiple defects were observed only in a minor proportion. Both prevalence and severity increased with age.

Adult↗

Is there etiologic heterogeneity between upper and lower neural tube defects?

Neural tube defects are thought to arise from two different embryologic mechanisms depending on the level of the defect: neurulation defects associated with anencephaly and upper spina bifida and canalization defects associated with lower spina bifida. To investigate whether the risk profiles of neural tube defect cases differ according to the level of the defect, the authors examined data from the Atlanta Birth Defects Case-Control Study. Cases were infants live- or stillborn from 1968 to 1980 with these defects, and controls were infants without defects randomly selected and frequency matched to cases by race, birth year, and hospital of birth. By multivariate polychotomous logistic regression, 1,186 controls were compared with cases: 145 with anencephaly, 59 with upper spina bifida (cervical/thoracic lesions), and 100 with lower spina bifida (lumbar/sacral lesions). Infant's sex and sibling recurrence of neural tube defects were the only factors for which the case subgroups significantly differed in risk. The risks associated with selected maternal exposures during the first trimester of pregnancy did not differ among the case subgroups. Although these results do not support the concept that upper and lower neural tube defects differ in risks from exogenous factors, differences in sibling recurrence and in risks by sex between the two groups suggest an underlying heterogeneity in genetic susceptibility factors.

Anencephaly↗

Quantitative assessment of cranial defect healing and correlation with the expression of TGF-beta.

Circular parietal defects from 3 to 12 mm in diameter were made in 45 6-month old skeletally mature guinea pigs, and animals were sacrificed after survival periods of 3 days to 12 weeks. The original defect was harvested in continuity with a rim of surrounding bone and the adjacent dura and pericranium. After 12 weeks, all 3 and 5 mm defects were completely covered by a bridge of bone, while residual defects were noted within the 8 and 12 mm wounds. Percentage of new bone formation was significantly higher within 3 mm defects, than in all larger defects at each time interval from 1 week on (P < .05), reaching a mean of 93% in 3 mm defects and remaining below a mean of 31% in the remaining defect sizes. Immunolocalization demonstrated an osteogenic front in which the osteoblasts stained strongly for all isoforms of TGF-beta, with the intensity decreasing after the majority of the defects had reossified; this front was located at the advancing bone edge of the defect as well as the endocranial side adjacent to the dura. In conclusion, isoforms of TGF-beta are upregulated during a limited "window" of time corresponding to the period of calvarial reossification, and are localized to osteoblasts within an osteogenic front at the periphery and dural surfaces of the defects.

Animals↗

Follow-up of perfusion defects in pulmonary perfusion scanning after pulmonary embolism: are we too careless?

Persisting perfusion defects may still be found in pulmonary perfusion scintigraphy months or years after pulmonary embolism. The aim of this study was to investigate the rate of persisting perfusion defects and the pattern of scintigraphic follow-up of patients after pulmonary embolism. Only those patients were included into our study who received pulmonary perfusion scintigraphy between 1991 and 1999, and who had perfusion defects including at least one whole segment. These perfusion defects were considered as persisting perfusion defects if unchanged over at least 1 year. From 3640 patients examined, 451 (12.4%) had perfusion defects meeting the criteria of this study. Of those, 129 (28.6%) received a scintigraphic follow-up. In 62 patients (48.1%), a reperfusion of the defects was found. In 38 patients (29.5%), the defects persisted within a follow-up period of up to 12 weeks. However, no pulmonary perfusion scintigraphy was performed thereafter. Out of the 129 patients receiving a scintigraphic follow-up, only 29 (22.5%) had a follow-up over more than 1 year, 19 of those had persisting perfusion defects. It is concluded that our data show an inadequate scintigraphic follow-up of patients with pulmonary embolism which may lead to unnecessary anticoagulant treatment if persisting perfusion defects are misinterpreted as fresh pulmonary embolism. In many cases, there was no further follow-up even if reperfusion of the defects was lacking in early follow-up.

Adult↗

Leukocyte adhesion deficiency III: a group of integrin activation defects in hematopoietic lineage cells.

PURPOSE OF REVIEW: In the last 2-3 years our understanding of leukocyte adhesion cascades has increased, mainly in defining new pathways by which integrin activation occurs on circulating leukocytes recruited to sites of inflammation. While defects in the integrin structure (leukocyte adhesion deficiency (LAD) I) and in the selectin glycoprotein ligand biosynthesis (LAD II) have been described in the past few decades, a newly recognized defect in the activation of integrins (LAD III) was only recently delineated. The clinical manifestations and molecular basis of this syndrome and related cases will be reviewed. RECENT FINDINGS: While in LAD I and II the defect in the adhesion cascade is restricted to leukocytes, all four cases of LAD III described to date also had defects in platelet aggregation. These patients suffered from recurrent bacterial infections and a severe bleeding tendency. All cases were reported to have activation defects in all major integrin subfamily members expressed in circulating leukocytes and platelets. In one case there was a defect in Rap1, which is a crucial protein in the inside-out and outside-in (ligand-induced) signaling underlying integrin activation mainly by cytokines. In this case, both chemokines and cytokines were unable to activate Rap1 leading to severe adhesive defects analyzed in vitro. SUMMARY: While in LAD I and II the primary genetic defect is known, in the newly described LAD III the primary event leading to the defect is still unknown, despite a clear biochemical defect in Rap1 activation. The molecular basis or the defect in integrin activation may be different in the various cases described so far. It seems logical, however, to assume that in all reported cases, a key component of inside-out signaling to integrins activation is involved.

Biotransformation↗

Correlation between topographic profiles of localized retinal nerve fiber layer defects as determined by optical coherence tomography and red-free fundus photography.

PURPOSE: To evaluate the topographic relationship of localized retinal nerve fiber layer (RNFL) defects as determined by optical coherence tomography (OCT) and by red-free fundus photography. METHODS: Sixty-five eyes of 65 patients with localized, wedge-shaped RNFL defects identified in red-free fundus photographs and with matching visual field defects were scanned with the Stratus OCT. On the resulting RNFL thickness report printout, segments of the line graph outside of the 95 and 99% normal limits were defined as "5% OCT defect" and "1% OCT defect," respectively. Correlations between the angular location and angular width of RNFL defects as determined by OCT (OCT defects) and by red-free fundus photography (red-free defects) were evaluated. RESULTS: Angular locations and widths of both 5 and 1% OCT defects were significantly correlated with corresponding red-free defects (all P values<0.001). CONCLUSIONS: There is a strong topographic correlation between characteristics of localized RNFL defects as determined by OCT and red-free photography.

Adult↗

Bone regeneration in cranial defects previously treated with radiation.

OBJECTIVES/HYPOTHESIS: Bone reconstruction in the head and neck region is frequently performed in the context of previous radiation treatment. Thus, the effectiveness of tissue engineering approaches for regenerating bone in radiated defects needs to be determined before considering application to patients. Incomplete healing is described when using osteoinductive protein therapy alone for bone defects previously treated with radiation. We hypothesized that a different approach using ex vivo gene therapy can heal these severely compromised defects. STUDY DESIGN: Animal study using Fisher rats. METHODS: Two weeks before surgery, rats received either no radiation or a 12 Gray radiation dose to the calvarium. Syngeneic dermal fibroblasts were transduced ex vivo using an adenoviral vector containing the cDNA for bone morphogenetic protein (BMP)-7. Critical-sized calvarial defects were created, and either a transduced cell-seeded scaffold or an autologous bone graft was placed into the defect. Nonradiated defects were harvested 4 weeks later for both groups. Radiated defects treated with bone grafts were harvested at 4 weeks, and those treated with gene therapy were harvested either at 4 or 8 weeks. Gross inspection and histology were used to evaluate wound healing. RESULTS: None of the bone grafts had gross or histologic evidence of healing at the wound margins. The nonradiated gene therapy treated defects revealed gross and histologic near-100% bone regeneration by 4 weeks after surgery. By gross inspection, the radiated defects had soft tissue admixed with islands of bone at both 4 and 8 weeks. The histologic appearance revealed areas of dense bone in a nonconfluent pattern admixed with adjacent cells having the morphologic appearance of hypertrophic chondrocytes, suggesting continued endochondral ossification. CONCLUSIONS: Preoperative radiation significantly impairs the ability of BMP-7 ex vivo gene therapy to heal rat critical-sized cranial defects. This finding has significant implications for translating this tissue engineering approach to patients with cancer-related segmental bone defects.

Animals↗

Reconstruction of extensive composite mandibular defects with large lip involvement by using double free flaps and fascia lata grafts for oral sphincters.

BACKGROUND: Extensive composite mandibular defects involving large lip defects are the most difficult to repair among head and neck reconstructions. This study presents the authors' approach using double free flaps and fascia lata grafts for oral sphincters. METHODS: Ten patients were studied after ablative oral cancer surgery. Segmental defects of the mandible ranged from 6 to 14 cm. Cheek defects ranged from 9 x 6 cm to 15 x 12 cm, and intraoral defects ranged from 9 x 7 cm to 16 x 16 cm. Upper lip defects ranged from 10 percent to 50 percent, and lower lip defects ranged from 50 percent to 90 percent. A fibula osteocutaneous flap was used for reconstruction of mandibular defects and intraoral lining, and an anterolateral thigh flap was used for cheek and lip defects. Then, a sheet of fascia lata graft was used to reconstruct the oral sphincter. The tendon graft was passed into the subcutaneous layers of the reconstructed lip, woven into the remaining orbicularis oris muscle of the lip, and anchored to the upper lip near the philtral columns to complete the oral ring with adequate tension. RESULTS: Free flap survival was 100 percent. Complications included one patient with neck hematoma and distal anterolateral thigh flap necrosis, three patients with neck wound infection, and one patient with osteomyelitis of the mandible. All but one patient had adequate oral competence. All the patients were able to resume a soft diet. The speech ability was nearly normal for all the patients, and all the patients had gained an acceptable appearance. CONCLUSIONS: For extensive composite mandibular defects combined with large lip defects, immediate reconstruction with double free flaps and a fascia lata graft for oral sphincter has proved to be a useful option for better functional and cosmetic results.

Adult↗

Biodegradable polylactide membranes for bone defect coverage: biocompatibility testing, radiological and histological evaluation in a sheep model.

Large bony defects often show a delayed healing and have an increasing risk of infection. Several materials are used for the coverage of large defects. These materials must be biocompatible, easy to use, and must have an appropriate stability to present a mechanical hindrance. Aim of this study was to investigate two different biodegradable membranes for defect coverage in a sheep model. Round cranial defects (1.5 cm diameter) were created in sheep. Six different treatments were investigated: defects without membrane, defects covered with a poly(D,L-lactide) or with a 70/30 poly(L/D,L-lactide) membrane and all defects with or without spongiosa filling. The sheep were sacrificed 12 or 24 weeks postoperatively. Bone formation in the defects was quantified by computer-assisted measurements of the area of the residual defect on CT radiographs. Histomorphometry and host-tissue response were evaluated by light microscopy. The biocompatibility was investigated by analyzing the amount of osteoclasts and foreign body cells. Both membranes served as a mechanical hindrance to prevent the prolapse of soft tissue into the defect. The biocompatibility test revealed no differences in the amount and distribution of osteoclasts at the two investigated time points and between the investigated groups. No negative effect on the tissue regeneration was detectable between the investigated groups related to the type of membrane, but a foreign body reaction around the two membrane types was observed. In the membrane-covered defects, the spongiosa showed a progressing remodeling to the native bony structure of the cranium. The groups without spongiosa partly revealed new bone formation, without complete bridging in any group or at any time point. Comparing the 12 and 24 weeks groups, an increased bone formation was detectable at the later time point. In conclusion, the results of the present in vivo study reveal a good biocompatibility and prevention of soft tissue prolapse of the two used membranes without differences between the membranes. An enhanced remodeling of the spongiosa into native bony structures under the membranes was detectable, but no osteopromoting effect was observed due to the membranes.

Absorbable Implants↗

Resolution of bone defects of varying dimension and configuration in the marginal portion of the peri-implant bone. An experimental study in the dog.

BACKGROUND: It was demonstrated that a marginal defect of about 1 mm between the bone wall and the metal surface after implant installation can heal with a high degree of bone fill and osseointegration. OBJECTIVE: The aim of the present animal experiment was to study bone healing at implant sites with hard tissue defects of varying dimensions and configuration. MATERIAL AND METHODS: Four Labrador dogs were used. All mandibular premolars and first molars were extracted. After 3 months of healing, five experimental sites, two control (C1, C2) and three test (T1, T2, T3) sites, were identified. In all five sites, custom-made implants with a sand-blasted, large-grit, acid-etched (SLA) surface and with an outer dimension of 3.3x10 mm, were used. In site C1, traditional implant installation was performed. In site C2, the marginal 5 mm of the canal, prepared for the implant, was widened to 5.3 mm using a step-drill. Thus, following the installation of the implant, a circumferential gap occurred between the bone tissue and the metal rod that was 5 mm deep and between 1 and 1.25 mm wide. In test site T1, the canal was widened to establish a marginal gap of 2-2.25 mm. In test sites T2 and T3, the marginal 5 mm of the canal was first widened to 5.3 mm (T2) or 7.3 mm (T3). The buccal bone wall opposite the defect was subsequently removed. Following the placement of a cover screw in sites C2, T1, T2, and T3, a resorbable membrane was placed over the defect. All implants were submerged. After 4 months of healing, block biopsies of each implant site were dissected and processed for ground sectioning. RESULTS: The observations disclosed that four-wall defects of different dimensions (1-2.25 mm wide) that occurred in the marginal portion of the recipient sites following implant installation were resolved during healing. Further, at sites where the buccal bone wall during defect preparation was intentionally removed, healing resulted in defect resolution at the mesial, distal, and lingual aspects. At the buccal aspects, healing was incomplete but the dimension of the defect was reduced by the limited amounts of new bone formation extending from the lateral and apical borders of the defect. CONCLUSION: Wide marginal defects may during healing be filled with bone. In such defects a high degree of osseointegration may occur to implants designed with an SLA surface.

Absorbable Implants↗

Isolation and characterization of new proliferating cell nuclear antigen (POL30) mutator mutants that are defective in DNA mismatch repair.

A number of studies have suggested a role for proliferating cell nuclear antigen (PCNA) in DNA mismatch repair (MMR). However, the majority of mutations in the POL30 gene encoding PCNA that cause MMR defects also cause replication and other repair defects that contribute to the increased mutation rate caused by these mutations. Here, 20 new pol30 mutants were identified and screened for MMR and other defects, resulting in the identification of two mutations, pol30-201 and pol30-204, that appear to cause MMR defects but little if any other defects. The pol30-204 mutation altered an amino acid (C81R) in the monomer-monomer interface region and resulted in a partial general MMR defect and a defect in MSH2-MSH6 binding in vitro. The pol30-201 mutation altered an amino acid (C22Y) located on the surface of the PCNA trimer that slides over the DNA but did not cause a defect in MSH2-MSH6 binding in vitro. The pol30-201 mutation caused an intermediate mutator phenotype. However, the pol30-201 mutation caused almost a complete defect in the repair of AC and GT mispairs and only a small defect in the repair of a "+T" insertion, an effect similar to that caused by an msh6Delta mutation, indicating that pol30-201 primarily effects MSH6-dependent MMR. The chromosomal double mutant msh3-FF>AA msh6-FF>AA eliminating the conserved FF residues of the PCNA interacting motif of these proteins caused a small (<10%) defect in MMR but showed synergistic interactions with mutations in POL30, indicating that the FF>AA substitution may not eliminate PCNA interactions in vivo. These results indicate that the interaction between PCNA and MMR proteins is more complex than was previously appreciated.

Amino Acid Motifs↗