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Exosomes derived from mesenchymal stem cells are an active area of research due to their therapeutic potential in treating osteoporosis. To further harness their therapeutic performance in modulating bone resorption, we have equipped exosomes with osteoclast-targeting moieties on their surface as well as chemokine receptor antagonists blocking osteoclast recruitment. Phosphatidylserine (PS), a membrane lipid exerting immunosuppressive and phagocytic signals, was incorporated in the membrane of exosome mimetics (EMs) to achieve a marked affinity for osteoclast precursors and potential anti-resorptive effects. We also aimed to tackle a CXCL9-CXCR3 ligand-receptor axis, a critical signaling axis in regulating osteoclast precursor recruitment and differentiation at bone resorption sites, by encapsulating a chemical antagonist of CXCR3, AMG487, in the PS-incorporated EMs (PS-EMs). The osteoclast-targeting PS-EMs loaded with AMG487 effectively protected against bone loss in an ovariectomized mouse model. Our findings demonstrate the great promise of PS-EMs as anti-resorptive nanotherapies for alleviating osteoporosis., Competing Interests: The authors declare no competing financial interest.

Background: Medication related osteonecrosis of the jaws (MRONJ), a rare side-effect of antiresorptive medications, is described as exposed bone in the oral cavity that lasts for at least 8 weeks. Most studies report a female predilection for MRONJ; these findings could be due to the increased use of antiresorptives in females, or due to inherent differences between male versus female patients., Purpose: The purpose of this study was to measure and compare the incidence and severity of osteonecrosis of the jaws (ONJ) between male and female mice., Study Design, Setting, Sample: We designed a randomized in-vivo animal study utilizing male and female mice treated with zoledronic acid (ZA). Experimental periodontitis was induced in 24 male and 24 female mice using a silk ligature following administration of saline or a potent bisphosphonate. After 8 weeks, animals were evaluated radiographically and histologically., Independent Variable: The independent variables were sex (male vs female) and treatment group (ZA vs saline control). Treatment was randomly assigned with balanced distribution between male and female animals., Main Outcome Variable: The main outcome variable was ONJ status coded as present or absent. ONJ was defined as present if there was histologic contact between the ligature and the alveolar bone. Secondary outcomes of interest were radiographic and histologic parameters., Analysis: Statistical differences were analyzed using a two-way analysis of variance with Tukey's post hoc test using a P value of 0.05 for significance., Results: The final sample was composed of 24 vehicle treated and 24 ZA treated animals. In vehicle treated animals, 8% of female and 8% of male animals developed ONJ. In ZA treated animals, 83% of female and 92% of male animals developed ONJ. Sex was not associated with the risk (measured as incidence of disease) for developing ONJ or in the radiographic or histologic parameters that were assessed (P values >.1)., Conclusions: Sex does not appear to affect the incidence of MRONJ or the severity of the disease as assessed by the radiographic and histologic parameters., (Copyright © 2024 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the outcomes of immediate and delayed implant placement with bone-level tapered implants., Materials and Methods: In this post-market, multicenter prospective randomized controlled study with a primary endpoint of 1 year, 53 patients were randomized to receive either immediate implant placement (test group) or delayed implant placement (control group). The mean crestal bone level changes from implant loading to 12 months postloading were measured using standardized digital periapical radiographs. Changes in facial plate thickness (as measured on CBCT images), implant success and survival, implant stability, soft tissue changes, patient-centered outcomes, and adverse events were measured to assess outcomes between the test and control treatments at 12 months postloading., Results: Of the original 53 patients, 46 patients completed the study (23 in each group). Mean bone changes from loading to the 12-month follow-up were recorded with no statistically significant difference (P = .950) between the groups. The hypothesis was confirmed that immediate implant placement (test) in extraction sockets produces in similar outcomes as delayed placement (control). The test group was found to be similar to the control group (P = .022) in terms of mean changes in facial plate thickness. Implant survival and success were 95.8% in the test group and 92% in the control group. Stability in the control group was superior at the time of surgery, but there was no difference between the groups at implant loading, producing a nonsignificant P value of .563)., Conclusions: This randomized controlled multicenter study showed comparable outcomes 1 year after prosthetic loading in the immediate and delayed implant placement groups.

The bone morphogenetic protein (BMP) signaling pathway plays a crucial role in bone development and regeneration. While BMP-2 is widely used as an alternative to autograft, its clinical application has raised concerns about adverse side effects and deteriorated bone quality. Therefore, there is a need to develop more sophisticated approaches to regulate BMP signaling and promote bone regeneration. Here, we present a novel complementary strategy that targets both BMP antagonist noggin and agonist Trb3 to enhance bone defect repair without the application of exogenous BMP-2. In vitro studies showed that overexpression of Trb3 with simultaneous noggin suppression significantly promotes osteogenic differentiation of mesenchymal stem cells. This was accompanied by increased BMP/Smad signaling. We also developed sterosome nanocarriers, a non-phospholipid liposomal system, to achieve non-viral mediated noggin suppression and Trb3 overexpression. The gene-loaded sterosomes were integrated onto an apatite-coated polymer scaffold for in vivo calvarial defect implantation, resulting in robust bone healing compared to BMP-2 treatments. Our work provides a promising alternative for high-quality bone formation by regulating expression of BMP agonists and antagonists., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Immediate implant placement and loading is a practice that continues to gain traction in implant dentistry because it reduces treatment time and improves satisfaction. Novel implant designs that facilitate increased primary stability, while not compromising osseointegration and long-term survival are important to offer immediate solutions for missing teeth. Here, we hypothesize that fully tapered implants can obtain successful osseointegration with high survival rates after immediate loading in fresh extraction sockets and healed sites., Materials and Methods: A total of 13 swine with 73 implants were evaluated. Fully tapered or apically tapered implants were placed in extraction sockets and healed sites. Insertion torque and resonance frequency analysis were determined at placement and euthanasia. Animals were evaluated at: placement, and 1-week and 12-weeks after placement. Bone to Implant Contact (BIC), Bone Area/Total Area (BA/TA), and first BIC (fBIC) analyses were conducted., Results: The fully tapered implant achieved similar primary stability with lower insertion torque at placement. Apically and fully tapered implants had comparable BIC (50.1% vs 59.4%) and ISQ (82.5 vs 80.3) values by 12 weeks in healed sites. In extraction sockets, BIC and ISQ for the apically tapered implant was 35.8% and 73.2 and 37.8% and 79.2 for the fully tapered implants, respectively., Conclusions: In this short-term study, immediately loaded fully tapered implants obtained high survival with similar osseointegration ability as apically tapered implants when placed in healed sites and fresh extraction sockets. Fully tapered implants show promise for use in immediate loading and immediate placement., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)