Immediately provisionalized tapered conical connection implants for single-tooth restorations in the maxillary esthetic zone: a 5-year prospective single-cohort multicenter analysis.

OBJECTIVES: This open, single-cohort, multicenter, prospective study investigated the efficacy of immediately provisionalized tapered conical connection implant for single-tooth restorations in the anterior and premolar regions of the maxilla after 5 years of function. MATERIALS AND METHODS: All implants were placed in healed sites and immediately provisionalized. MBLs, soft-tissue parameters, and oral-health impact profile (OHIP) were evaluated at implant insertion, 6, 12, 24, 36, and 60 months. Paired Wilcoxon signed-rank tests and Kaplan-Meier survival analysis was used for statistical and implant survival/success analyses, respectively. RESULTS: Seventy-seven patients (81 implants) completed the 5-year follow-up. The 5-year cumulative survival and success rates were 97.8%, and the mean MBL change from implant insertion to 5 years was - 0.80 ± 1.13 mm. Optimal papilla index scores were observed at 90.1% of sites at 5 years compared with 32.8% of sites at insertion. Pink esthetic score, modified bleeding and plaque indices, and OHIP showed statistically significant improvement at the 5-year follow-up. CONCLUSIONS: Immediately provisionalized tapered conical connection implants promote marginal bone stability and excellent esthetic outcomes after 5 years of function. CLINICAL RELEVANCE: This treatment is a viable option for patients requiring immediately provisionalized single-tooth restorations in the esthetic zone and shows favorable long-term clinical outcomes, including marginal bone stability and excellent esthetics.

A prospective multicenter evaluation of immediately functionalized tapered conical connection implants for single restorations in maxillary anterior and premolar sites: 3-year results.

OBJECTIVES: This multicenter prospective clinical trial investigated immediately provisionalized, anodized, conical connection, tapered implants with platform shifting in maxillary anterior and premolar sites. MATERIALS AND METHODS: Patients requiring single-tooth implant-supported restorations in maxillary anterior and premolar sites were enrolled. Implants were immediately provisionalized and evaluated at insertion, 6 months, and annually thereafter. Outcome measures were marginal bone level change (ΔMBL), cumulative survival rate (CSR), and success rate, soft-tissue parameters, and oral health impact profile (OHIP). ΔMBL and Pink Esthetic Score were analyzed using Wilcoxon signed-rank tests. CSR was calculated using life table analysis. Other soft-tissue parameters were analyzed using sign tests. RESULTS: Of 94 enrolled patients (99 implants), 84 (88 implants) attended the 3-year follow-up. After an initial bone loss between implant insertion and 6 months (- 0.92 ± 1.23 mm), bone levels stabilized from 6 months to 3 years (0.13 ± 0.94 mm) with no significant change. The 3-year CSR was 98.9%, and the cumulative success rate was 96.9%. Papilla index scores of 2 or 3 were observed at 88.6% of sites at the 3-year visit compared with 32.8% at implant insertion. Improvements were observed for all other outcomes, including bleeding on probing, esthetics, plaque, and OHIP. CONCLUSIONS: This restorative protocol was associated with high primary stability, patient satisfaction, stable bone levels, and an overall improvement of the soft tissue outcomes over a 3-year period. CLINICAL RELEVANCE: The presented treatment is a viable option for single-tooth restorations of maxillary anterior teeth and premolars with successful short- to mid-long-term clinical outcomes.

An open prospective single cohort multicenter study evaluating the novel, tapered, conical connection implants supporting single crowns in the anterior and premolar maxilla: interim 1-year results.

OBJECTIVES: The aim of this multicenter prospective clinical study was to evaluate anodized tapered implants with a conical connection and integrated platform shifting placed in the anterior and premolar maxilla. MATERIALS AND METHODS: The study enrolled patients requiring single-tooth restorations in healed sites of maxillary anterior and premolar teeth. All implants were immediately temporized. Clinical and radiographic evaluations were conducted at implant insertion, 6 months, and 1 year. Outcome measures included bone remodeling, cumulative survival rate (CSR), success rate, soft-tissue health and esthetics, and patient satisfaction. Bone remodeling and pink esthetic score were analyzed using Wilcoxon signed-rank tests. CSR was calculated using life table analysis. Other soft-tissue outcomes were analyzed using sign tests. RESULTS: Out of 97 enrolled patients (102 implants), 87 patients (91 implants) completed the 1-year visit. Marginal bone remodeling was -0.85 ± 1.36 mm. After the expected initial bone loss, a mean bone gain of 0.11 ± 1.05 mm was observed between 6 months and 1 year. The CSR was 99.0%, and the cumulative success rate was 97.0%. Partial or full papilla was observed at 30.8% of sites at baseline, 87.2% at 6 months, and 90.5% at 1 year. Soft-tissue response, esthetics, and patient satisfaction all improved during the study period. CONCLUSIONS: Bone gain was observed following the expected initial bone loss, and soft-tissue outcomes improved suggesting favorable tissue response using anodized tapered conical connection implants. CLINICAL RELEVANCE: Rapid stabilization of bone remodeling and robust papilla regeneration indicate favorable tissue healing promoted by the conical connection, platform-shift design. TRIAL REGISTRATION: clinicaltrials.gov NCT02175550.

Alveolar bone regeneration in response to local application of calcitriol in vitamin D deficient rats.

AIM: Vitamin D deficiency is considered to diminish bone regeneration. Yet, raising the serum levels takes months. A topic application of the active vitamin D metabolite, calcitriol, may be an effective approach. Thus, it becomes important to know the effect of vitamin D deficiency and local application on alveolar bone regeneration. MATERIAL AND METHODS: Sixty rats were divided into three groups; two vitamin depletion groups and a control group. Identical single defects (2 mm diameter) were created in the maxilla and mandible treated with calcitriol soaked collagen in one deficiency group while in the other two groups not. Histomorphometric analysis and micro CTs were performed after 1 and 3 weeks. Serum levels of 25(OH)D3 and PTH were determined. RESULTS: Bone formation rate significantly increased within the observation period in all groups. Bone regeneration was higher in the maxilla than in the mandible. However, bone regeneration was lower in the control group compared to vitamin depletion groups, with no significant effects by local administration of calcitriol (micro CT mandible p = 0.003, maxilla p < 0.001; histomorphometry maxilla p = 0.035, mandible p = 0.18). CONCLUSION: Vitamin D deficiency not necessarily impairs bone regeneration in the rat jaw and a single local calcitriol application does not enhance healing.

Dimethyloxalylglycine lyophilized onto bone substitutes increase vessel area in rat calvarial defects.

AIM: Pharmacological inhibitors of prolyl hydroxylases, also termed hypoxia-mimetic agents (HMAs), when repeatedly injected can support angiogenesis and bone regeneration. However, the possible role of HMA loaded onto bone substitutes to support angiogenesis and bone regeneration under diabetic condition is unknown. The capacity of HMA loaded onto deproteinized bovine bone mineral (DBBM) to support angiogenesis and bone formation was examined in diabetic Wistar rats. METHODS: Diabetes was induced by intraperitoneal injection of streptozotocin. The HMA dimethyloxalylglycine (DMOG) and desferrioxamine (DFO) were lyophilized onto DBBM. Calvarial defects were created with a trephine drill and filled with the respective bone substitutes. After 4 weeks of healing, the animals were subjected to histological and histomorphometric analysis. RESULTS: In this report, we provide evidence that DMOG loaded onto DBBM can support angiogenesis in vivo. Specifically, we show that DMOG increased the vessel area in the defect site to 2.4% ± 1.3% compared with controls 1.1% ± 0.48% (P = 0.012). There was a trend toward an increased vessel number in the defect site with 38.6 ± 17.4 and 31.0 ± 10.3 in the DMOG and the control group (P = 0.231). The increase in angiogenesis, however, did not translate into enhanced bone formation in the defect area with 9.2% ± 7.1% and 8.4% ± 5.6% in DMOG and control group, respectively. No significant changes were caused by DFO. CONCLUSIONS: The results suggest that DMOG loaded onto DBBM can support angiogenesis, but bone formation does not increase accordingly in a type 1 diabetic rat calvarial defect model at the indicated time point.

Impact of dietary vitamin D on osseointegration in the ovariectomized rat.

AIM: Vitamin D deficiency is highly prevalent in the population and associated with impaired peri-implant bone regeneration. Yet, there is a gap in understanding the impact of vitamin D supplementation on the process of osseointegration. In this study, the effect of vitamin D supplementation on peri-implant bone regeneration was investigated. METHODS: Fifty ovariectomized Sprague-Dawley rats were divided into three groups. The depletion group was fed a vitamin D-free diet for 8 weeks. The repletion group received vitamin D-free diet for 6 weeks, before animals were switched to standard diet containing 2400 IU/kg vitamin D. The control group was fed the standard diet. Two titanium mini-implants were placed in the tibia. All groups remained on their previous diet until sacrifice. Blood sample testing and histomorphometric analysis were performed. RESULTS: Vitamin D depletion caused a significant reduction in 25-hydroxvitamin D in rat serum that returned to control levels in the repletion group. This vitamin deficiency was associated with a decrease in bone-to-implant contact in the cortical area, which was leveled to controls in the repletion group. No significant changes by vitamin D depletion were noticed in the medullar compartment. Moreover, also the peri-implant bone area and the mineral apposition rate remained unchanged upon vitamin D depletion. CONCLUSION: These results indicate that vitamin D deficiency has a negative impact on cortical peri-implant bone formation in ovariectomized rats, which can be compensated by vitamin D supplementation. This study provides first insight into the potential beneficial effect of vitamin D supplementation in implant dentistry.

Human adipose derived stem cells reduce callus volume upon BMP-2 administration in bone regeneration.

INTRODUCTION: The demand for new therapeutic approaches to treat bone defects and fractures is increasing in trauma surgery and orthopaedics because the number of patients with degenerative diseases is continuously growing. "Tissue Engineering" offers promising new technologies that combine the three components - cells, growth factors and matrix. Efforts are targeted at improving and accelerating recovery, especially for long bone fractures, and reducing the risk of delayed bone healing or pseudoarthrosis. Adult human adipose-derived stem cells (ASC) can differentiate into osteoblasts in an osteogenic surrounding. Bone morphogenetic protein-2 (BMP-2) accelerates and initiates this differentiation. Fibrin, a matrix that promotes wound healing, is a promising carrier for ASCs and BMP-2. MATERIALS AND METHODS: In this study, a 2mm transcortical drill hole in the femur of male rats served as a small non-critical size defect model for fracture simulation. In vivo bone healing was investigated upon administration of the growth factor BMP-2 embedded with ASCs in a locally applied fibrin matrix. Groups with the components alone were also investigated. After 2 and 4 weeks, µCT and histology were performed to determine the bone and callus volume. RESULTS AND DISCUSSION: After only a short period of time (2 and 4 weeks), this animal model discloses comparative information about the osteogenetic potential and bone regeneration with little effort (no osteosynthesis necessary). The most significant result found in this model is that the combination of ASCs and BMP-2 in a fibrin matrix significantly reduces callus formation after 2 weeks compared to BMP-2 alone. BMP-2 alone significantly increased callus formation. ASCs embedded alone in the fibrin matrix did not lead to increased bone regeneration. CONCLUSION: Transplantation of ASC modulated the callus induction by BMP-2 to a normal volume.

Long-term effects of magnetron-sputtered calcium phosphate coating on osseointegration of dental implants in non-human primates.

OBJECTIVES: To determine the effect of magnetron-sputtered calcium phosphate coating of implants on the later stages of osseointegration in a non-human primate model. MATERIAL AND METHODS: Eighteen and 20 implants with a 0.1 microm amorphous calcium phosphate coating and a turned surface, respectively, were inserted in the anterior upper and lower jaw of adult non-human primates. Following a 7.5 months healing period, one part of the implants remained in the submerged position. The other part of implants was connected to healing abutments to allow peri-implant inflammation to occur. After another 20 months, histologic and histomorphometric analysis of the peri-implant area was performed. RESULTS: Submerged implants with a calcium phosphate coating and a turned surface showed no signs of an inflammatory reaction. The histomorphometric parameters 'bone volume per tissue volume' (BV/TV) and 'bone-to-implant contacts' (BIC) were not affected by calcium phosphate coating. Non-submerged implants of both groups showed occasionally signs of inflammation at the implant-abutment junction. Histomorphometric analysis revealed that the distance between the implant-abutment junction and the most coronal level (where bone was attached to the implant) as well as BV/TV and BIC were independent from the surface modification. CONCLUSION: Our results show that dental implants with calcium phosphate coating behave similar to turned implants independently whether they are connected to healing abutments or remain submerged. Ultra-thin calcium phosphate coating can combine the positive effects of calcium phosphate during the early stage of osseointegration without causing impairment of the later stages.

[Bisphosphonate-associated osteonecrosis of the jaw]. / Bisphosphonat-assoziierte Osteonekrosen des Kieferknochens.

Intravenous application of bisphosphonates (BP) represents an established therapeutic strategy of tumor-associated bone metastasis and severe hypercalcemia. Patients can develop osteonecrosis of the jaw (ONJ) as a side effect of this therapy. The diagnosis of ONJ is based on three criteria: a) patients have been or are currently treated with BP; b) a deficiency in wound healing, which is in 70-80% associated with necrotic alveolar bone, characteristically exposed, is present for at least 8 weeks and c) no radiotherapy of the head and neck was performed. The suppression of bone turnover, concomitant with high functional load of the alveolar bone, and the subsequent accumulation of microfractures are considered the main pathologic factors of this disease. The cumulative incidence of ONJ lies approximately between 1 and 10% in oncologic patients, being associated with the antiresorptive potency and the respective molecular structure of the BPs. Patients with multiple myeloma develop ONJ more frequently than patients with other oncological diseases such as metastasizing breast- and prostate cancer, a fact that may also be due to the higher transfusion/injection frequency of BP in these patients. Dental treatment strategies are responsible for the occurrence of ONJ in approximately 80% of cases. Based on a clinical staging, patients can be grouped into three categories and should receive the corresponding treatment regime. Prospective clinical studies are required for a better understanding of etiology and pathogenesis of ONJ to make treatment, risk estimation and prognosis of ONJ more accurate.

Bone marrow stromal cells of young and adult rats respond similarly to platelet-released supernatant and bone morphogenetic protein-6 in vitro.

BACKGROUND: Age-related changes in periodontal bone regeneration, osseointegration of dental implants, and graft consolidation are increasingly considered in treatment planning. This study was intended to show whether aging is associated with a diminished responsiveness of osteoprogenitor cells to growth and differentiation factors. METHODS: We compared the capacity of bone marrow stromal cells harvested from young and adult rats to proliferate, migrate, and differentiate into the osteogenic lineage following exposure to platelet-released supernatant (PRS) or bone morphogenetic protein-6 (BMP-6). Bone marrow stromal cells were isolated from 12 young rats aged 6 weeks and 12 adult rats aged 9 months. Proliferation was assessed by 3[H]thymidine incorporation, migration was evaluated with the Boyden chamber assay, and osteogenic differentiation was deduced from alkaline phosphatase activity. RESULTS: Irrespective of the donor age, bone marrow stromal cells showed increased mitogenic activity and chemotactic motility when exposed to PRS. Adult bone marrow stromal cells had higher alkaline phosphatase activities at baseline and upon incubation with BMP-6 than cells obtained from young animals. There was no difference between the two groups in the slope of the alkaline phosphatase activity curve following stimulation with BMP-6. CONCLUSIONS: The data demonstrate that, irrespective of their age, bone marrow stromal cells respond similarly to PRS and BMP-6 under in vitro conditions. These findings suggest that osteoprogenitor cells within the bone marrow of adult rats retain their juvenile potential to respond to growth and differentiation factors, which are released naturally or are applied therapeutically at sites of bone regeneration.

Combined enzymatic and antioxidative treatment reduces ischemia-reperfusion injury in rabbit skeletal muscle.

BACKGROUND: Ischemia/reperfusion (I/R) injury is characterized by the production of oxygen-free radicals leading to disturbances in vasomotility (microvascular constriction) and microvascular permeability (interstitial edema formation). The objective was to evaluate the effect of the combined antioxidative and enzymatic preparation Phlogenzym on I/R injury of skeletal muscle. MATERIALS AND METHODS: A rabbit hindlimb model of I/R (2.5/2 h) was used (IR group). Phlogenzym, containing rutin, trypsin, and bromelain, was applied enterally (60 mg/kg body weight) as a bolus 30 min prior to ischemia (Ph group). Sham-operated animals served as controls (CO group). Plasma malondialdehyde, potassium, and microvascular perfusion (monitored by laser flowmetry) were assessed. Histomorphometry and electron microscopy were performed from major adductor muscles. RESULTS: Two hours after reperfusion, potassium levels were significantly elevated in IR compared to Ph group (6.7 +/- 1.2 versus 4.9 +/- 0.9 mmol/l, P < 0.006). Enhanced lipid peroxidation, apparent by increased plasma malondialdehyde levels, was ameliorated in the Ph group (1.0 +/- 0.1 versus 0.7 +/- 0.1 nmol/ml, P < 0.0001). No-reflow (reduction of blood flow by 62% in IR group) was not observed in the Ph group (P < 0.004). Phlogenzym treatment prevented microvascular constriction (17.6 +/- 2.3 versus 12.6 +/- 1.1 microm(2), P < 0.0001) and mollified interstitial edema (21.5 +/- 2.0 versus 26.0 +/- 3.7%, P < 0.017), resulting in mild ultrastructural alterations in contrast to pronounced sarcolemmal and mitochondrial damage in untreated rabbits. CONCLUSIONS: Phlogenzym had a protective effect on skeletal muscle during I/R injury expressed by prevention of no-reflow and preservation of muscle tissue.

Ischemia/reperfusion injury of skeletal muscle: plasma taurine as a measure of tissue damage.

BACKGROUND: Cell membrane rupture by oxygen-derived free radicals is a systematic feature of ischemia/reperfusion (I/R) injury. High taurine concentration gradients in skeletal muscle prompted us to evaluate whether plasma taurine levels (pTau) are a useful marker of I/R injury after different periods of ischemia. METHODS: Rabbits were randomly assigned to either 1 or 2.5 hours of hind-limb ischemia followed by 2 hours of reperfusion (groups IR1 [n = 12] and IR2.5 [n = 13], respectively). Corresponding sham groups (SHAM1 [n = 8] and SHAM2.5 [n = 9]) were used as controls. Analyzed parameters included histomorphometry and electron microscopy of skeletal muscle biopsies, pTau, and plasma level of malondialdehyde. Skeletal muscle function was assessed 3 weeks after I/R injury. RESULTS: No significant morphologic changes were detectable at the end of ischemia. After reperfusion, mild interstitial edema with intact muscle cell membranes developed in IR1 group; pTau was not increased. IR2.5 group, by contrast, showed severe interstitial edema formation (interfiber area increased by 112%, P <.005), microvascular constriction (microvessel area decreased by 33%, P <.0005), and damage to the muscle cell membranes that was confirmed by the increased plasma malondialdehyde. pTau was higher than in the SHAM2.5 group (P <.0005). Pronounced cell damage in IR2.5 group resulted in impaired muscle function (maximal tetanic tension was reduced 2 times, P <.005) but not in IR1 group. CONCLUSION: Skeletal muscle tolerates 1 h/2 h but not 2.5 h/2 h of I/R, the latter resulting in interstitial edema formation, microvascular constriction, and a late muscle dysfunction. Cell membrane rupture through stimulated lipid peroxidation promotes leakage of intracellular taurine, leading to increased pTau after reperfusion and may be considered as prognostically unfavorable in terms of organ function reversibility. In the rabbit model, pTau seems to be a sensitive marker of I/R injury to skeletal muscle.

S-nitroso human serum albumin treatment reduces ischemia/reperfusion injury in skeletal muscle via nitric oxide release.

BACKGROUND: Peroxynitrite generated from nitric oxide (NO) and superoxide (O2-) contributes to ischemia/reperfusion (I/R) injury. Feedback inhibition of endothelial NO synthase by NO may inhibit O2- production generated also by endothelial NO synthase at diminished local L-arginine concentrations accompanying I/R. METHODS AND RESULTS: During hindlimb I/R (2.5 hours/2 hours), in vivo NO was monitored continuously (porphyrinic sensor), and high-energy phosphates, reduced and oxidized glutathione (chromatography), and I/R injury were measured intermittently. Rabbits receiving human serum albumin (HSA) (controls) were compared with those receiving S-nitroso human serum albumin (S-NO-HSA) beginning 30 minutes before reperfusion for 1 hour or 30 minutes before ischemia for 3.5 hours (0.1 micromol x kg(-1) x h(- 1)). The onset of ischemia led to a rapid increase of NO from its basal level (50+/-12 nmol/L) to 120+/-20 and 220+/-15 nmol/L in the control and S-NO-HSA-treated groups, respectively. In control animals, NO dropped below basal levels at the end of ischemia and to undetectable levels (<1 nmol/L) during reperfusion. In S-NO-HSA-treated animals, maximal NO levels never decreased below basal concentration and on reperfusion were 100+/-15 nmol/L (S-NO-HSA preischemia group, 175+/-15 nmol/L). NO supplementation by S-NO-HSA led to partial and in the preischemia group to total preservation of high-energy phosphates and glutathione status in reperfused muscle (eg, preischemia groups: ATP, 30.23+/-5.02 micromol/g versus control, 15.75+/-4.33 micromol/g, P<0.0005; % oxidized glutathione, 4.49+/- 1.87% versus control, 22.84+/-6.39%, P<0.0001). S-NO-HSA treatment in all groups led to protection from vasoconstriction and reduced edema formation after reperfusion (eg, preischemia groups: interfiber area, 12.94+/-1.36% versus control, 27.83+/-1.95%, P< 0.00001). CONCLUSIONS: Long-lasting release of NO by S-NO-HSA provides significant protection of skeletal muscle from I/R injury.