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Purpose: To explore the contribution of paired-related homeobox 1-positive (Prrx1+) cells to the implant-induced osseointegration process in adult alveolar bone and the potential underlying mechanisms. Materials and Methods: Cre recombinase-induced lineage tracing and cell ablation were conducted in a murine dental implant model. Scratch and transwell assays were used to assess MC3T3-E1 cell migration after paired-related homeobox 1 overexpression. Single-cell RNA sequencing was applied to identify potential genes involved in Prrx1+ cell-driven osteogenesis. Results: Prrx1+ cells were observed to accumulate in the peri-implant area in a time-dependent manner; the number of these cells was found to reach its maximum on day 14. Osseointegration in mice was noticeably impaired after ablation of Prrx1+ cells. Further, it was discovered that Prrxl promotes MC3T3-E1 cell migration, a process which is indispensable for sound healing of peri-implant tissue. Finally, semaphorin 3C (Sema3C) was detected exclusively and abundantly expressed by Prrx1+ cells. Knockdown of Sema3C in Prrx1+ cells significantly weakened their osteogenic potential. Conclusions: Our data suggest that Prrx1+ cells contribute to the osseointegration process under stress stimulation and Sema3C may play a critical role in Prrx1+ cell-driven osteogenesis. Prrxl could significantly promote MC3T3-E1 cell migration. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the feasibility of reversing a primary failure through therapeutic mechanical stimulation induced by transcutaneous application of acoustic waves (extracorporeal shockwave therapy [ESWT]) in the peri-implant tissues. Materials and Methods: This clinical report evaluates the outcome of a new protocol proposed to treat a primary failure (loosened oral implant): application of three cycles of ESWT (one session per week for 3 consecutive weeks) with an equivalent positive energy of 0.18 mJ/mm²(therapeutic dose: 2,000 pulses, 8 Hz, 4.0 bar). Standardized intraoral radiographs and CBCT scans were taken, the implant stability quotient (ISQ) was determined, and clinical evaluations were performed. Results: It was possible to verify a progressive increase in ISQ values after the ESWT protocol: 17 initially, 46 at 2 months, and 68 at 4 months. This led to successful implant prosthetic rehabilitation (35 Ncm). Follow-up evaluations at 6 years confirm that the new bone-implant interface is preserved and that ESWT is a safe, noninvasive treatment. Conclusions: In the context of the new dynamic model of osseointegration (the foreign body equilibrium), this represents the first report of a host-implant equilibrium reestablished after an early implant failure process. However, more studies are needed to determine both the medical device and the most effective therapeutic range for clinical applications of this technology in oral implantology. [ABSTRACT FROM AUTHOR]

Purpose: To examine the impact of two implant designs that promote different insertion torque values on implant stability and to histomorphometrically evaluate the bone healing after immediate implant placement in fresh sockets in a sheep model. Materials and Methods: Twelve female sheep (mean weight: 35.0 ± 5.0 kg) were included in the study. Additionally, 48 conical Morse taper dental implants were included, comprising two groups (n = 24 per group): Group 1, where the implant design can provide high insertion torque values; and Group 2, where the implant design can provide low insertion torque values. Both had the same surface treatment and dimensions (4.0 x 10 mm). The mandibular first and second molars on both sides were extracted carefully. Sequentially, osteotomies were made in the mesial socket of each molar tooth. The final implant position was 2 mm below the buccal bone crest level. On the right side, a Group 1 implant was placed anteriorly, with a Group 2 implant in the posterior position; on the left side, the Group 2 implant was anterior and the Group 1 implant was posterior. A digital torque meter was used to measure the maximum final insertion torque value (f-IT). The initial implant stability quotient (ISQ) was measured immediately after implant insertion (T0) and immediately after the euthanasia and removing the mandibles. The animals were euthanized (n = 6 animals/ time) at 21 days (T1) and 35 days (T2). To compare statistical differences for each analyzed intragroup parameter, f-test was used. Pearson's correlation was used to analyze possible correlations: f-IT and percentage of bone-to-implant contact (%BIC), f-IT and ISQ, and ISQ and %BIC. Results: Group 1 presented higher insertion torque values than Group 2, with a statistically significant difference (P < .0001). The ISQ mean values were higher in the buccolingual direction than those obtained in the mesiodistal direction for both groups. Higher %BIC measurements were seen in Group 2 than Group 1 samples at both times and in both directions. There were statistical differences between groups for new bone, medullary spaces, and collagen matrix at each evaluation time. Conclusions: Using implants with a modified macrogeometry plays a significant role in implant stability and bone tissue healing around the implant. It is important for clinicians to carefully consider implant macrogeometry when planning implant surgery to achieve optimal implant stability and successful osseointegration, mainly in cases of immediate implant placement. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the influence of immediate loading on the osseointegration and bone density of implants placed in a healed alveolar bone crest and supporting single crowns. Materials and Methods: Two solid titanium transmucosal mini-implants were placed in the distal regions of the mandible in 14 patients. One mini-implant was immediately functionally loaded, whereas the other was left unloaded. After 2 months of healing, biopsy samples were retrieved and the levels of new bone, old bone, and total bone (new + old) were assessed. Results: Histologic examination was performed on biopsies from 12 patients (n = 12). The new bone-to-implant contact percentage (BIC%) was 40.3% ± 16.8% and 55.1% ± 19.1% (P = .043) at the unloaded and loaded sites, respectively; in addition, the total BIC% was 44.9% ± 17.0% and 59.5% ± 18.8%, respectively (P = .034). The new bone density was 45.9% ± 11.6% for the unloaded implants and 45.9% ± 16.7% for the loaded implants (P = .622). Conclusions: Immediate loading had a positive effect on bone apposition at the implant surface, but no effect on bone density was observed after 2 months of healing. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the effect of simvastatin gel in the osseointegration of dental implants using bone scintigraphy. Materials and Methods: A total of 20 participants with missing mandibular first molars and D2 type bone were assigned equally to two groups. Group A received 1.2% simvastatin and group B received placebo gels during the placement of implants. The participants were subjected to bone scintigraphy to determine the osteoblastic activity at baseline, 30 days, and 90 days after implant placement. Results: Group A had a significant increase in osteoblastic activity between baseline, day 30, and day 90 (P < .05), with a higher mean of 100.06% ± 21.644% on day 30. Group B had a significant increase in osteoblastic activity only between baseline and day 30 and between baseline and day 90 (P < .05). There was no difference between days 30 and 90 (P > .05), with a higher mean of 79.20% ± 18.255% on day 30. A bivariate analysis performed at different time periods revealed a significant difference between groups A and B on day 30. Conclusions: Implants placed with 1.2% simvastatin gel showed enhanced osteoblastic activity in the 4th week after implant placement, indicating that there was a faster rate of osseointegration at an early stage. [ABSTRACT FROM AUTHOR]

Purpose: Marginal bone resorption (MBR) around dental implants may sometimes be a self-limiting condition due to balancing immunologic reactions against utilized materials rather than a progressive bacterial infection. Contrary to previous assumptions from ligature-induced experimental peri-implantitis studies, a recent 8-week experiment by the present authors showed that marginal ligatures trigger an inflammatory immune response, resulting in bone resorption around implants in the absence of plaque. The present study aimed to investigate whether this inflammatory/immunologic reaction attenuates or progresses toward implant failure after a longer healing time (12 weeks). Materials and Methods: Sterile silk ligatures were placed around the top of titanium (Ti) implants and compressed against the femoral cortical bone plate of six rabbits. A nonligated implant was used as a control. After 12 weeks of submerged healing, ground sections of implants and surrounding tissues were investigated with light microscopy. The marginal soft tissues were also analyzed using selected quantitative polymerase chain reaction (qPCR) markers. Results: Histologically, the ligatures were outlined by immune cells, including multinucleated giant cells (MNGCs), with adjacent fibrous encapsulation and resorbed peripheral bone that contrasted from the osseointegrated nonligated control implants. The difference in expression of qPCR markers was not significant, but > two-fold upregulation of markers CDIIb, IL1β, ARG1, NCF1, and CD4 and > twofold downregulation of CD8 indicated a mild, focal inflammatory/immune response against the ligatures compared to controls, with upregulation of M1 and M2 macrophages, neutrophils, and helper T-cells as well as downregulation of killer T cells. Further, the bone formation markers OC and ALPL were > two-fold downregulated (consistent with the lack of osseointegration of the ligatures) compared to control implants. Conclusions: Marginal silk ligatures trigger an inflammatory/immune response and aseptic bone resorption around implants. Compared to the previous 8-week study, the inflammatory reaction against the silk appears to attenuate with time, with only a mild persisting inflammation that may block osseointegration; instead, a fibrous tissue encapsulation-type reaction is maintained. This may explain why traditional ligature experiments have required regular exchange of ligatures for the bone resorption to progress. [ABSTRACT FROM AUTHOR]

Purpose: Dental implants are an established treatment option for varying edentulous conditions that has grown in popularity since the 1990s. This increased clinical application has shown a parallel increase in implant-related research. The objective of this paper was to perform a comprehensive bibliometric analysis of five dental implantology journals from 1991 to 2023. Materials and Methods: A search was done in the Web of Science database between 1991 and 2023 in five journals with a focus on dental implantology: Clinical Oral Implant Research, Clinical Implant Dentistry and Related Research, Implant Dentistry, The International Journal of Oral & Maxillofacial Implants, and International Journal of Oral Implantology. Results marked as a correction, retraction notice, retracted article, meeting abstract, or withdrawn publication were removed from the analysis. The time period analyzed was divided into four time periods, organized by decade: 1991 to 2000, 2001 to 2010, 2011 to 2020, and 2021 to 2023. Additionally, the top 100 cited papers were also exported separately. Authors and countries with most publications were tabulated from the Web of Science database. VOSviewer software was used to create network maps of keywords and title word occurrences for each of the time periods. HistCite software was used to analyze the number of publications and citation counts. Results: Network maps of keywords and title word occurrences suggested an early focus on osseointegration and titanium implants between 1991 and 2000. Publications between 2001 and 2010 saw a focus on in vivo studies, implant surface, and peri-implantitis. Publications from 2011 and later saw a focus on bone regeneration, complications, and zygomatic implants. The USA ranked highest in total number of publications in all analyzed time periods. Conclusions: Within the limitations of the present study, a comprehensive bibliometric analysis from 1990 to 2023 was reported. Trends in keywords and titles of implant publications were identified in these journals, which mirrored the trends seen in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of sinus membrane stabilization (via suturing) and dental implant placement on the endo-sinus bone formation in lateral sinus elevations performed without grafting. Materials and Methods: Maxillary sinus elevation surgery using the lateral approach was performed bilaterally on 30 New Zealand white rabbits. The maxillary sinus areas were divided into control and test groups. In the control group, a titanium screw was placed after sinus membrane elevation; in the test group, the sinus membrane was sutured to the lateral walls, and a titanium screw was placed in the center of the alveolar crest. The subjects were sacrificed at 4 and 8 weeks. Then samples were collected, and a microcomputed tomography (micro-CT) analysis was performed. In addition, the volume of newly formed bone, percentage of osseointegration, sinus volume, residual bone height, and implant protrusion length were measured using micro-CT analysis. Results: The sinus volume, volume of newly formed bone, and percentage of osseointegration in the test group were significantly higher than in the control group at 4 weeks (P = .01, P = .04, P = .02, respectively). While the volume of newly formed bone was 17.1 ± 3.08 mm3 in the control group, it was 26.9 ± 14.26 mm3 in the test group at 4 weeks. The volume of newly formed bone significantly decreased from 26.9 ± 14.26 mm3 to 17 ± 3.66 mm3 at 8 weeks (P = .02). No significant difference in residual bone height was found at 4 and 8 weeks (P = .07). No significant difference in implant protrusion length was found between the control and test groups (P = .18). Protrusion length and new bone formation in the sinus showed a negative relationship (P = .01). Conclusions: Suturing the sinus membrane to the lateral sinus wall is an effective approach for increasing osseointegration, bone volume, and sinus volume in the short term. A slow-absorbing suture material can be used to maintain sinus and bone volumes in the long term. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of interleukin-6 (IL-6) inhibitor (tocilizumab) on bacterial infection-associated bone resorption around implants during osseointegration in rabbits. Materials and Methods: At total of 24 male, 9-monthold New Zealand white rabbits were included, and their two mandibular anterior teeth were extracted. Three months after extraction, 24 one-piece Dentium implants (Ø 2.5 mm, intraosseous length of 12 mm) were inserted in the anterior mandible, and the rabbits were divided into four groups (n = 6 per group). Different treatment methods were used in each group: blank control group (BC); only silk ligation (negative control [NC]); silk ligation and injection with minocycline hydrochloride ointment (positive control [PC]); and silk ligation and injection with tocilizumab at 8 mg/kg via the auricle vein (experimental [EP]). Eight weeks later, the animals were sacrificed, and samples were collected and then analyzed using microcomputed tomography (microCT) scanning, immunohistochemical analysis, and histologic analysis. Results: From the microCT measurement, the ratio of the bone volume to the total volume (BV/TV) in the EP group was 67.00% ± 2.72%, which was higher than that in the other three groups (58.85% ± 2.43% in the BC group, 55.72% ± 2.48% in the PC group, and 36.52% ± 3.02% in the NC group). From immunohistochemical analysis, the expression of IL-6 was found to be higher in the NC group than in the BC, PC, and EP groups, but there was no statistical difference between these three groups. Furthermore, the RANKL (receptor activator of nuclear factor-κB ligand) expression was the lowest in the EP group, followed by the BC group, the PC group, and the NC group, which had the highest expression; there was no difference between the NC and PC groups. Upon histologic analysis, significant new bone was found on the implant surfaces in the EP group, sparse and less new bone could be seen in the BC and PC groups, and the most serious bone resorption occurred in the NC group. Conclusions: Tocilizumab, an inhibitor of IL-6, has a certain effect in preventing bone loss around implants caused by bacterial infection during the osseointegration period. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of combined therapy of teriparatide and raloxifene on the osseointegration of titanium dental implants in a rabbit model of osteoporotic bone. Materials and Methods: Sixty female rabbits were randomly divided into six groups. The sham ovariectomy group (control) consisted of animals that received no medication. Animals in the ovariectomy group (OVX) underwent ovariectomy and received no medication. The combined group consisted of ovariectomized animals that received combined teriparatide (10 mg/kg) for 12 weeks and raloxifene (10 mg/kg) for 12 weeks. The sequential group (SEQ) consisted of ovariectomized animals that received teriparatide (10 mg/kg) for the first 6 weeks and raloxifene therapy (10 mg/kg) for the following 6 weeks sequentially. The parathormone (PTH) and raloxifene (RAL) groups consisted of ovariectomized animals that received only teriparatide (10 mg/kg) for 12 weeks or raloxifene (10 mg/kg) for 12 weeks, respectively. Dental implants (Bilimplant) were placed in the proximal metaphysis of both tibias in all rabbits. Histomorphometric and microCT studies were performed on the specimens obtained from the right tibia bone. Removal torque (RTQ) and implant stability quotient (ISQ) tests were performed on the specimens obtained from the left tibia bone. The results were compared and evaluated statistically. Results: RTQ analysis revealed a statistically significant difference between the mean values of the combined group (93.01 ± 27.19 Ncm) and the OVX group (49.6 ± 12.5 Ncm) (P = .015). The highest mean T0 (implantation day) value was obtained in the control group (67.1 ± 3.4 Ncm), and the lowest mean value was obtained in the OVX group (61.4 ± 3.8 Ncm). The highest T1 mean (3 months after implantation) was obtained by the combined group (76.6 ± 3.8 Ncm), and the lowest mean was obtained by the OVX group (68.9 ± 6.2 Ncm). Histomorphometric analyses showed that the mean percentage of bone-to-implant contact (BIC%) of the combined group (51.2%) was significantly higher than that of the OVX group (28.6%) (P =.006). In the microCT examinations, it was found that the mean BIC% value of the combined group (41.1%) was significantly higher than that of the OVX group (24.1%) (P < .001). Conclusions: According to the results of the current study, combined therapy of teriparatide and raloxifene improves the BIC and osseointegration of titanium dental implants in osteoporotic bone compared with sequential or independent therapy with these agents. [ABSTRACT FROM AUTHOR]

Purpose: The structural and compositional similarities between dentin and alveolar bone form the basis for utilizing dentin for bone regeneration. Various authors have recommended using treated mineralized, partially demineralized, or demineralized dentin grafts instead of xenografts because of their comparable clinical and radiographic results and lower costs. The current study therefore compared the effect of untreated mineralized dentin grafts (UMDGs) versus xenografts in vertical and horizontal augmentation around dental implants that were immediately placed in the mandibular anterior region. Materials and Methods: A total of 56 patients who required immediate dental implant placement in the mandibular anterior region were randomly allocated to group I (study), where ground dentin was washed with normal saline and placed around the dental implants, or group II (control), where a xenograft was used. The primary implant stability was measured at the time of implant placement. Secondary implant stability, plaque index (PI), bleeding index (BI), probing depth (PD), and keratinized mucosa width (KMW) were assessed at baseline (time of definitive abutment and provisional crown placement) and then at 3, 6, and 12 months. Pain and the number of analgesics consumed were assessed daily during the first postoperative week. Marginal bone loss (MBL) and radiodensity were assessed radiographically. Results: There were no significant differences between the groups in terms of postoperative pain, the number of analgesic tablets consumed, peri-implant mucositis, or peri-implantitis. Both groups showed comparable results for the PI, BI, and PD. Moreover, there was no statistical difference between the groups with regard to primary implant stability and secondary implant stability at baseline and 12 months. Group I showed significantly lower secondary implant stability after loading at 3 and 6 months and significantly greater bone loss and lower bone density before exposure. KMW and MBL after exposure were significantly higher in group I at all time points. Conclusions: Although UMDGs showed similar clinical results to xenografts, including primary and secondary implant stability, they had higher resorption rates than xenografts. Therefore, treatment of the dentin graft is required. Thus, the authors do not recommend using UMDGs. [ABSTRACT FROM AUTHOR]

Purpose: To answer the following focus question: In preclinical in vivo experimental models, do oral implants placed in overdimensioned (OD) sites present greater biomechanical properties and histomorphometric parameters of osseointegration compared to implants placed in standard or undersized implant sockets? Materials and Methods: Online databases were searched for controlled animal studies reporting on OD sites up to February 2023. The relative implant-final drill discrepancy (IDD) was used to categorize the control and test groups according to surgical drilling protocol: (1) control: undersized (IDD > 0.5 mm) or standard (IDD = 0.2 to 0.5 mm); and (2) test OD: stress-free oversized (IDD = 0.0 to -0.1 mm); test GAP: friction-free oversized (IDD = -0.1 mm). Random-effects meta-analyses were performed for the outcomes of insertion and removal torque values (ITV and RTV, respectively), bone-to-implant contact (%BIC), and bone density (%BD) for short- (0 to 2 weeks), intermediate- (3 to 4 weeks), and long-term (= 5 weeks) healing periods. Results: Of the 527 records identified, 13 studies met the eligibility criteria. Histologically, the OD and GAP groups prevented ischemic necrosis and extensive bone resorption at the bone-implant interface in both the marginal cortical layer and the trabeculae. Faster and increased rates of bone formation, characterized by primary osteons and highly vascularized tissue, took place in OD sites between 1 and 5 weeks of healing. Meta-analyses indicated statistically significant benefits in favor of (1) control vs OD for short-term healing in extraoral sites, with pooled estimates (weighted mean difference) of ITV = 25.35 Ncm, %BIC = 2.10%, and %BD = 26.19%; (2) control vs OD for long-term healing in intraoral sites, with %BD = 11.69%; (3) control vs GAP for intermediate-term healing in extraoral sites, with %BD = 3.03%; and (4) control vs GAP for long-term healing in extraoral sites, with RTV = 5.57 Ncm. Conclusions: Oversized surgical preparation of the implant site does not seem to provide any additional benefit compared to standard or undersized sites regarding quantitative parameters of osseointegration. However, it does minimize marginal bone resorption and yields better-quality bone healing, despite the comparable results among different experimental animal models in the late postoperative period. [ABSTRACT FROM AUTHOR]

This assessment evaluated the clinical feasibility of using narrow-diameter implants to support a mandibular overdenture. Twelve patients presenting with an edentulous mandible were recruited from nine dental offices. Each patient received two to four implants in the mandible. The implants were placed without additional bone augmentation, and a total of 36 implants were placed. All sites achieved satisfactory crestal bone stability and soft tissue maintenance 1 year after the final prosthetic restoration. This investigation was supported by the Osseointegration Foundation, working in conjunction with the Zest Anchors implant company. There are three basic valuable activities that emerge from a professional foundation, which were reflected in this case study. They include disseminating information to practitioners, persuading young clinicians to become research investigators, and reaching out to patients in need of treatment who cannot afford it without a charitable opportunity. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of continuous perioperative clopidogrel treatment on the osseointegration of titanium implants. Materials and Methods: A total of 32 New Zealand rabbits were randomly divided between two groups: a clopidogrel group (n = 16) and a control group (n = 16). For 1 week prior to the surgical placement of a titanium implant in their medial femoral condyle, rabbits in the clopidogrel group received 3 mg/kg of clopidogrel daily, and the control group received only the vehicle. This treatment was continued for another 6 weeks postoperatively. At 6 weeks, the rabbits were euthanized and postmortem histologic and histomorphometric evaluation of the implants was performed. Results: The surgical procedures and postoperative period were uneventful and well tolerated by all animals without any surgical wound dehiscence, signs of infection, or other complication. No implant failure was observed in any of the groups. Histomorphometric analysis showed that bone-to-implant contact (BIC) was 48.77% for the clopidogrel group and 34.65% for the control group, with statistically significant difference between them (P < .001). Moreover, clopidogrel group had significantly greater bone tissue density (40.52% vs 28.74%, respectively; P <.001) and mean trabecular thickness (284.7 μm vs 180.7 μm, respectively; P < .001) in proximity to the implant surface than the control group, while the mean trabecular number had no difference between groups (1.56 vs 1.60, respectively; P = .961). Conclusions: The present study showed that continuous clopidogrel treatment does not negatively affect osseointegration, but rather promotes it in terms of BIC and bone density around the titanium implants. Further studies on the effect of the P2Y12 receptor and its antagonists on peri-implant bone homeostasis may provide useful information or applications for long-term success of dental implant therapy. [ABSTRACT FROM AUTHOR]