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The purpose of the present study was to evaluate the Morse effect of different internal tapered implant-abutment connections (ITCs) using a pullout test. Implants with different ITCs were selected: Short (Bicon, USA), G1; Novo Colosso (Medens, Brazil), G2; Epkut (SIN, Brazil), G3; Strong SW (SIN, Brazil), G4; Flash (Conexão, Brazil), G5 and Bone Level (Straumann, Switzerland), G6. The respective computer-aided design (CAD) files were loaded into the analysis software to measure each ITC's taper angle and implant-abutment contact area. Six implants from each group were embedded in acrylic resin blocks, and the respective universal abutments were fixed using a mallet (G1) or by applying 20 Ncm of torque (G2 to G6). After 10 minutes, each abutment's retention screw was removed, and the force necessary for abutment rupture was recorded using a universal testing machine at a crosshead speed of 0.5 mm/min. The groups were compared using a one-way analysis of variance and Tukey's test. Spearman's correlation was used to check the correlation of the taper angle and contacting area with the pullout strength. G1, a no-screw abutment with a 3° taper, and G2, a 10° tapered abutment tightened by 20 Ncm, presented the highest pullout strength (P < .05). The increased taper angle of G4, compared to G3, reduced the Morse effect despite their similar implant-abutment contacting areas (P < .05). The G5 and G6 abutments loosened after screw removal and did not exhibit pullout resistance. The closer the tapered angle (r = -.958) and the higher the implant-abutment contact area (r = .880), the higher the pullout strength (P < .001). Within the limits of this study, the Morse effect is different among tapered implant-abutment connections. The closer the tapered angle and the higher the interface area, the higher the Morse effect between the abutment and the implant.

The objectives of the study group focused on the following main topics related to the performance of 1- and 2-piece ceramic implants: defining bone-implant-contact percentages and its measurement methods, evaluating the pink esthetic score as an esthetic outcome parameter after immediate implantation, recognizing the different results of ceramic implant designs as redefined by the German Association of Oral Implantology, incorporating the patient report outcome measure to include satisfaction and improvement in oral health-related quality of life, and conducting preclinical studies to address existing gaps in ceramic implants. During the Joint Congress for Ceramic Implantology (2022), the study group evaluated 17 clinical trials published between 2015 and 2021. After extensive discussions and multiple closed sessions, consensus statements and recommendations were developed, incorporating all approved modifications. A 1-piece implant design features a coronal part that is fused to the implant body or interfaces with the postabutment restoration platform, undergoing transmucosal healing. Long-term evaluations of this implant design are supported by established favorable clinical evidence. Inaccuracies in the pink esthetic score and bone-implant-contact percentages were managed by establishing control groups for preclinical studies and randomizing clinical trials. The patient-reported outcome measures were adjusted to include an individual visual analog scale, collected from each clinical study, that quantified improved oral health and quality of life. Preclinical investigations should focus on examining the spread of ceramic debris and the impact of heat generation on tissue and cellular levels during drilling. Further technical advancements should prioritize wound management and developing safe drilling protocols.

This study aimed to compare the effectiveness of platelet-rich fibrin clot (PRF) and conventional oroantral communication (OAC) repair techniques following tooth extractions from the maxilla. The study involved 22 patients, divided into 2 groups: a study group treated with PRF and a control group undergoing conventional OAC repair. The primary outcome measured was the effectiveness of OAC closure, with pain intensity and postoperative complications as secondary outcomes. Cone-beam computed tomography (CBCT) was used to evaluate post-extraction bone regeneration. Pain was assessed using the Visual Analogue Scale (VAS) on days 0, 1, 7, and 14 postoperatively. The results showed that the PRF group experienced a significant decrease in pain within the first 24 hours and after 7 days (P < .0001; P < .05). In contrast, complications were reported in 45.45% of patients in the conventional repair group and 18.18% in the A-PRF group. Three months postsurgery, CBCT revealed appreciable bone healing in both groups, with no significant difference (P > .05). In conclusion, the study suggests that A-PRF treatment for OACs resulted in fewer complications and quicker pain reduction than traditional repair methods, making it a promising alternative for managing OACs. However, future studies are needed to confirm these findings and establish the full therapeutic potential of PRF.

Since the delivery of biologic drugs to the brain is greatly hampered by the existence of the blood-brain barrier (BBB), brain shuttles are being developed to enhance therapeutic efficacy. As we have previously shown, efficient and selective brain delivery was achieved with TXB2, a cross-species reactive, anti-TfR1 VNAR antibody. To further explore the limits of brain penetration, we conducted restricted randomization of the CDR3 loop, followed by phage display to identify improved TXB2 variants. The variants were screened for brain penetration in mice using a 25 nmol/kg (1.875 mg/kg) dose and a single 18 h timepoint. A higher kinetic association rate to TfR1 correlated with improved brain penetration in vivo. The most potent variant, TXB4, showed a 3.6-fold improvement over TXB2, which had on average 14-fold higher brain levels when compared to an isotype control. Like TXB2, TXB4 retained brain specificity with parenchymal penetration and no accumulation in other organs. When fused with a neurotensin (NT) payload, it led to a rapid drop in body temperature upon transport across the BBB. We also showed that fusion of TXB4 to four therapeutic antibodies (anti-CD20, anti-EGFRvIII, anti-PD-L1 and anti-BACE1) improved their brain exposure between 14- to 30-fold. In summary, we enhanced the potency of parental TXB2 brain shuttle and gained a critical mechanistic understanding of brain delivery mediated by the VNAR anti-TfR1 antibody.

Systematic evaluations regarding the influence of PRF in ridge sealing are still lacking. To the best of our knowledge, this is the first systemic randomized, controlled, clinical approach dealing with the potential of a systematic applied solid PRF on soft tissue socket healing of molar and premolar extraction sockets with evaluation for up to 90 days. Qualitative and quantitative image analysis showed that PRF contributed to a significantly faster ridge sealing, within the period of 7-10 days in both tooth types. This led to a visibly less contraction at the PRF-treated group sites at day 90. Patients' pain perception demonstrated no statistic significance between both groups (PRF vs. natural healing), but the patients in PRF group seemed to have had less pain throughout the observational period. It becomes evident that PRF is able to serve as a promotor of the secondary wound healing cascade. The guiding capacity of PRF accelerating the process of open ridge healing makes it possible to act as a natural growth factor drug delivery system, providing a more predictable guided open wound healing of the ridge with less contraction of the soft tissue, the latter being a key factor for the subsequent successful dental implantation and oral rehabilitation.

Single domain shark antibodies that bind to the transferrin receptor 1 (TfR1) on brain endothelial cells have been used to shuttle antibodies and other cargos across the blood brain barrier (BBB) to the brain. For these studies the TXB4 brain shuttle was fused to a TrkB neurotrophin receptor agonist antibody. The TXB4-TrkB fusion retained potent agonist activity at its cognate receptor and after systemic administration showed a 12-fold increase in brain levels over the unmodified antibody. Only the TXB4-TrkB antibody fusion was detected within the brain and localized to TrkB positive cells in the cortex and tyrosine hydroxylase (TH) positive dopaminergic neurons in the substantia nigra pars compacta (SNc), where it was associated with activated ERK1/2 signaling. When tested in the 6-hydroxydopamine (6-OHDA) mouse model of Parkinson's disease (PD), TXB4-TrkB, but not the unmodified antibody, completely prevented the 6-OHDA induced death of TH positive neurons in the SNc. In conclusion, the fusion of the TXB4 brain shuttle allows a TrkB agonist antibody to reach neuroprotective concentrations in the brain parenchyma following systemic administration.

Single domain shark variable domain of new antigen receptor (VNAR) antibodies can offer a viable alternative to conventional Ig-based monoclonal antibodies in treating COVID-19 disease during the current pandemic. Here we report the identification of neutralizing single domain VNAR antibodies selected against the severe acute respiratory syndrome coronavirus 2 spike protein derived from the Wuhan variant using phage display. We identified 56 unique binding clones that exhibited high affinity and specificity to the spike protein. Of those, 10 showed an ability to block both the spike protein receptor binding domain from the Wuhan variant and the N501Y mutant from interacting with recombinant angiotensin-converting enzyme 2 (ACE2) receptor in vitro. In addition, three antibody clones retained in vitro blocking activity when the E484K spike protein mutant was used. The inhibitory property of the VNAR antibodies was further confirmed for all 10 antibody clones using ACE2 expressing cells with spike protein from the Wuhan variant. The viral neutralizing potential of the VNAR clones was also confirmed for the 10 antibodies tested using live Wuhan variant virus in in vitro cell infectivity assays. Single domain VNAR antibodies, due to their low complexity, small size, unique epitope recognition, and formatting flexibility, should be a useful adjunct to existing antibody approaches to treat COVID-19., (© 2021 Federation of American Societies for Experimental Biology.)

Transfer across the blood-brain barrier (BBB) remains a significant hurdle for the development of biopharmaceuticals with therapeutic effects within the central nervous system. We established a functional selection method to identify high affinity single domain antibodies to the transferrin receptor 1 (TfR1) with efficient biotherapeutic delivery across the BBB. A synthetic phage display library based on the variable domain of new antigen receptor (VNAR) was used for in vitro selection against recombinant human TfR1 ectodomain (rh-TfR1-ECD) followed by in vivo selection in mouse for brain parenchyma penetrating antibodies. TXB2 VNAR was identified as a high affinity, species cross-reactive VNAR antibody against TfR1-ECD that does not compete with transferrin or ferritin for receptor binding. IV dosing of TXB2 when fused to human Fc domain (TXB2-hFc) at 25 nmol/kg (1.875 mg/kg) in mice resulted in rapid binding to brain capillaries with subsequent transport into the brain parenchyma and specific uptake into TfR1-positive neurons. Likewise, IV dosing of TXB2-hFc fused with neurotensin (TXB2-hFc-NT) at 25 nmol/kg resulted in a rapid and reversible pharmacological response as measured by body temperature reduction. TXB2-hFc did not elicit any acute adverse reactions, bind, or deplete circulating reticulocytes or reduce BBB-expressed endogenous TfR1 in mice. There was no evidence of target-mediated clearance or accumulation in peripheral organs except lung. In conclusion, TXB2 is a high affinity, species cross-reactive, and brain-selective VNAR antibody to TfR1 that rapidly crosses the BBB and exhibits a favorable pharmacokinetic and safety profile and can be readily adapted to carry a wide variety of biotherapeutics from blood to brain., (© 2020 Federation of American Societies for Experimental Biology.)

The scientific community's understanding of how the SARS-CoV-2 virus is transmitted and how to best mitigate its spread is improving daily. To help protect patients from acquiring COVID-19 from a dental office nosocomial infection, many state or local governments have classified dental treatments as "nonessential" and have paused routine dental care. Dentists have been instructed to perform only procedures designated as emergencies. Unfortunately, there is not a good understanding of what a dental emergency is among governmental leaders. What a government agency may perceive as an elective procedure may be seen as "essential" by the dental clinician responsible for maintaining the oral health of the patient. Each dental specialty understands the effects delayed care has on a patient's oral and systemic health. Dentistry has made extensive progress in improving oral health through prevention of the dental emergency. The dental profession must work together to prevent the reversal of the progress dentistry and patients have made. This American Academy of Implant Dentistry (AAID) White Paper discusses what COVID-19 is and how it impacts dental treatments, presents guidelines for dentistry in general and for dental implant related treatments, specifically. Recommendations for implant dentistry include the following: (1) what constitutes a dental implant related emergency, (2) how patients should be screened and triaged, (3) what personal protective equipment is necessary, (4) how operatories should be equipped, (5) what equipment should be used, and (6) what, when, and how procedures can be performed. This paper is intended to provide guidance for the dental implant practice so patients and dental health care providers can be safe, and offices can remain open and viable during the pandemic.

Transferrin receptor 1 (TfR1) mediated transcytosis is an attractive strategy to enhance brain uptake of protein drugs, but translation remains a challenge. Here, a single domain shark antibody VNAR fragment (TXB2) with similar affinity to murine and human TfR1 was used to shuttle protein cargo into the brain. TXB2 was fused to a human IgG1 Fc domain (hFc) or to the amyloid-β (Aβ) antibody bapineuzumab (Bapi). TXB2-hFc displayed 20-fold higher brain concentrations compared with a control VNAR-hFc at 18 hours post-injection in wt mice. At the same time point, brain concentrations of Bapi-TXB2 was threefold higher than Bapi. In transgenic mice overexpressing human Aβ, the brain-to-blood concentration ratio increased with time due to interaction with intracerebral Aβ deposits. The relatively stable threefold difference between Bapi-TXB2 and Bapi was observed for up to 6 days after injection. PET imaging and ex vivo autoradiography revealed more parenchymal distribution of Bapi-TXB2 compared with Bapi. In conclusion, the TXB2 VNAR shuttle markedly increased brain uptake of protein cargo and increased brain concentrations of the Aβ binding antibody Bapi., (© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Several different biomaterials are being introduced for clinical applications. However, no current material-specific systematic studies define parameters for evaluating these materials. The aim of this retrospective animal study is to classify biomaterials according to the in vivo induced cellular reaction and outline the clinical consequence of the biomaterial-specific cellular reaction for the regeneration process. A retrospective histologic analysis was performed for 13 polymeric biomaterials and 19 bone substitute materials (BSMs) (of various compositions and origins) that were previously implanted in a standardized subcutaneous model. Semiquantitative analyses were performed at days 3, 15, and 30 after implantation according to a standardized score for the induction of multinucleated giant cells (MNGCs) and vascularization rate. The induced cellular reaction in response to different polymeric materials allowed their classification according to the MNGC score in the following groups: class I induced no MNGCs at any time point, class II induced and maintained a constant number of MNGCs over 30 days, and class III induced MNGCs and provided an increasing number over 30 days. All BSMs induced MNGCs to varying extents. Therefore, the resultant BSM classifications are as follows: class I induced MNGCs with a decreasing number, class II induced and maintained constant MNGCs over 30 days, and class III induced MNGCs with increasing number over 30 days. These observations were mostly related to the biomaterial physicochemical properties and were independent of the biomaterial origin. Consequently, the induction of MNGCs and their increase over 30 days resulted in disintegration of the biomaterial. By contrast, the absence of MNGCs resulted in an integration of the biomaterial within the host tissue. This novel classification provides clinicians a tool to assess the capacity and suitability of biomaterials in the intended clinical indication for bone and soft tissue implantations.