Comparing Single Tooth Implant Placement With and Without Allogenic Soft Tissue Augmentation. A Randomized Clinical Trial.

OBJECTIVE: To explore the effect of adding an allogenic soft tissue graft at time of single implant placement using a fully digital workflow for single implant placement and restoration without making either analog or digital impressions. MATERIALS AND METHODS: A prospective randomized clinical study was performed enrolling thirtynine participants requiring single tooth implant randomized into (+ graft) group which received an allogenic dermal graft at the time of implant placement (n=19), or (- graft) group (n=20). A fully digital surgical and restorative protocol was implemented. Intraoral scans were taken before implant placement (T0), at time of final crown delivery (T1) and at one-year post placement (T2). Intraoral scans were aligned using Geomagic Control X 2020 software), linear and volumetric changes in buccal tissues were measured at T0, T1 and T2. Implant survival, probing depths, and complications were recorded. Participants were asked to complete an OHIP-14 survey at T0 and T2. Marginal bone levels were measured at T0 and T2 on peri-apical x-rays. RESULTS: 39 participants completed surgery and restoration in incisor, canine, premolar and molar positions. Two early failures were recorded in central incisor positions (95% survival). Crown delivery without complication from the digital workflow (impressionless) was achieved for 36/39 of cases (92%) with implant depth control being implicated as the chief challenge. Thirtyseven participants attended the one-year follow-up visit. Both groups showed gain in buccal tissues thickness without significant differences between the two groups for both linear and volumetric measurements (P>0.05). Soft tissue grafting was associated with minimal added morbidity. The interproximal marginal bone changes recorded were -0.16mm mesial and - 0.12mm distal for the graft group and -0.01mm mesial and -0.11mm distal for the non-graft group (p=0.07 for mesial and 0.83 for distal). OHIP score was significantly reduced at T2 compared to T0 (P=0.003) for the entire cohort. CONCLUSIONS: The augmentation of alveolar mucosa on the buccal aspect of single tooth implants is associated with clinically favorable outcomes. A fully digital workflow has been validated to permit crown delivery on CAD/CAM abutments without implant impressions.

Evaluation of nanoscale versus hybrid micro/nano surface topographies for endosseous implants.

We examined the effect of a nanoscale titanium surface topography (D) versus two hybrid micro/nanoscale topographies (B and OS) on adherent mesenchymal stem cells (MSCs) and bone marrow derived macrophages (BMMs) function in cell culture and in vivo. In the in vitro study, compared to OS and B surfaces, D surface induced earlier and greater cell spreading, and earlier and profound mRNA expression of RUNX2, Osterix and BMP2 in MSCs. D surface induced earlier and higher expression of RUNX2 and BMP2 and lower expression of inflammatory genes in implant adherent cells in vivo. Measurement of osteogenesis at implant surfaces showed greater bone-to-implant contact at D versus OS surfaces after 21 days. We explored the cell population on the D and OS implant surfaces 24 h after placement using single-cell RNA sequencing and identified distinct cell clusters including macrophages, neutrophils and B cells. D surface induced lower expression and earlier reduction of inflammatory genes expression in BMMs in vitro. BMMs on D, B and OS surfaces demonstrated a marked increase of BMP2 expression after 1 and 3 days, and this increase was significantly higher on D surface at day 3. Our data implicates a dynamic process that may be influenced by nanotopography at multiple stages of osseointegration including initial immunomodulation, recruitment of MSCs and later osteoblastic differentiation leading to bone matrix production and mineralization. The results suggest that a nanoscale topography (D) favorably modulates adherent macrophage polarization toward anti-inflammatory and regenerative phenotypes and promotes the osteoinductive phenotype of adherent mesenchymal stem cells. STATEMENT OF SIGNIFICANCE: Our manuscript contains original data developed to define effects of a novel nanotopography on the process of osseointegration at the cell and tissue level.  Few studies have compared the effects of a nanoscale surface versus the more typical hybrid micro/nano-scale surfaces used today. We have utilized single-cell RNA sequencing for the first time to identify earliest cell populations on implant surfaces in vivo. We provide data indicating that the nanoscale surface acts upon both osteoprogenitor and immune cell (macrophages) to alter the process of bone formation in a surface-specific manner. This work represents new observations regarding osseointegration and immunomodulation.

Comparative Osteogenesis of Three Clinical Bone Graft Materials: An In Vivo Study.

PURPOSE: To investigate bone regeneration among three different bone graft materials in a rat calvarum model. MATERIALS AND METHODS: A total of 24 rats had two 5-mm defects placed per calvarial. Rats were divided into four groups: bovine xenograft (XG), demineralized bone matrix (DBM), mineralized bone graft (MBG), and collagen membrane control (CC). Within each group, samples were collected at two time points: 4 weeks (T4) and 8 weeks (T8). Bone regeneration was assessed by microcomputed tomography (micro-CT) imaging and was analyzed using MATLAB software. Additionally, the fixed samples were subsequently demineralized for immunohistochemistry and histomorphometry. Slides were mounted and stained with hematoxylin and eosin (H&E) stain as well as bone morphogenetic protein 2 (BMP-2) and runt-related transcription factor 2 (RUNX2) markers. The numbers of positive cells/area were calculated for each group and analyzed. RESULTS: At 4 weeks, DBM showed low mineral density (7.7%) compared to the control (25.2%), but increased dramatically at 8 weeks (DBM, T8 = 27.6%; CC, T8 = 27.2%). Xenograft material showed an increase in mineral desnity between T4 and T8 (XG, T4 = 25.0%; XG, T8 = 32.3%). MBG remained consistent over the 8-week trial period (MBG, T4 = 30.4%; MBG, T8 = 30.4%). BMP-2 expression was present in cells adherent to all graft materials. RUNX2 expression was also observed in cells adherent to all graft materials, indicating that during the 4- to 8-week healing period, all materials supported osteogenesis. CONCLUSIONS: Compared to other materials, the DBM had high osteoinductive properties during the 4- to 8-week time period based on increased mineral content. All materials were associated with immunohistologic evidence of osteogenesis in the rat calvarial defect model.

Can patients detect peri­implant mucosal inflammation? Results from a multicentre randomized trial.

PURPOSE: The objective of this study was to compare patient-reported outcomes (PROs) of peri­implant soft tissue inflammation and aesthetics around single-tooth implants in the anterior maxillary region with three different implant-abutment interface designs. METHODS: Participants were randomized to one of three different types of implant-abutment interface designs [Conical (CI), flat-to-flat (FI), and Platform Switched (PS)]. Implants and provisional crowns with prefabricated titanium abutments were placed 5 months following extraction and/or ridge augmentation. Permanent ceramic crowns with zirconia abutments were placed after 12 weeks. To assess PROs, appearance and inflammation questionnaires were completed from provisional crown placement to the 3-year follow-up. RESULTS: Tooth appearance at the 3-year follow-up revealed a difference amongst CI, FI and PS implants (p=0.049; Kruskal-Wallis test). PS was rated better than FI (p=0.047) at 1 year for appearance of soft-tissue and satisfaction with colour. There were no differences for self-consciousness, smile and pain/discomfort while eating/hard food items. CONCLUSIONS: Although participants tended to rate the health of mucosa around PS implants as slighty better than the other two implant systems, the differences were minimal and inconsistent. Thus, patient satisfaction in terms self-perceived gingival health and esthetics was high for all 3 systems tested, suggesting that patients are unable to detect mucosal inflammation. CLINICAL SIGNIFICANCE: Patients find it difficult to perceive mucosal inflammation; hence, it is recommended that patients attend implant follow-up visits, even if they do not perceive inflammation. The study suggests that there is a relationship between the PROs and the clinical outcomes of tested implants.

Macrogeometric Differentiation of Dental Implant Primary Stability: An In Vitro Study.

PURPOSE: To evaluate an alternative cutting, progressive thread design to increase primary stability in low-density bone. MATERIALS AND METHODS: Four different implants with different macrogeometries (Nobel Biocare Active [NA] Internal RP implants [4.3 × 11.5 mm], Straumann BLX Roxolid RB implants [4.5 × 10 mm], Astra Tech Implant EV implants [4.2 × 11 mm], and PrimeTaper [PT 4.2 × 11 mm]) were placed in simulated osteotomies and extraction sockets in synthetic bone (Sawbones) according to the manufacturers' protocol. Insertion torque and ISQ values were measured using Implantmed Plus motor and Ostell IDX, respectively. Insertion time was recorded. Average values were calculated and compared using ANOVA and Tukey test. RESULTS: Insertion torque (range: 5 to 44 Ncm) increased with increasing synthetic bone density for all implants. Different ISQ values in synthetic low-density bone were not observed in higher-density synthetic bone. Insertion torque of all implants was reduced when implants were placed in simulated sockets compared to simulated osteotomies. In both low-density and higher-density synthetic bone, the primary stability of PrimeTaper implants with cutting and progressive thread design was equivalent to that of the Nobel Biocare NobelActive implant with compressive thread design and greater than the BLX implant with compressive thread design. CONCLUSION: Different implant macrogeometries obtain relatively high primary stability in low-density bone when measured by ISQ. Doublethread implant designs reduce insertion times in higher-density bone. A cutting and progressive compressing thread design provides density-sensing performance compared to aggressive condensing thread designs. This macrogeometry can achieve high primary stability associated with modest insertion torque compared to aggressive threaded implant designs known to attain the highest insertion torque. The presence of multiple cutting threads may offer advantages in obtaining primary stability in low-density bone.

Topography-mediated immunomodulation in osseointegration; Ally or Enemy.

Osteoimmunology is at full display during endosseous implant osseointegration. Bone formation, maintenance and resorption at the implant surface is a result of bidirectional and dynamic reciprocal communication between the bone and immune cells that extends beyond the well-defined osteoblast-osteoclast signaling. Implant surface topography informs adherent progenitor and immune cell function and their cross-talk to modulate the process of bone accrual. Integrating titanium surface engineering with the principles of immunology is utilized to harness the power of immune system to improve osseointegration in healthy and diseased microenvironments. This review summarizes current information regarding immune cell-titanium implant surface interactions and places these events in the context of surface-mediated immunomodulation and bone regeneration. A mechanistic approach is directed in demonstrating the central role of osteoimmunology in the process of osseointegration and exploring how regulation of immune cell function at the implant-bone interface may be used in future control of clinical therapies. The process of peri-implant bone loss is also informed by immunomodulation at the implant surface. How surface topography is exploited to prevent osteoclastogenesis is considered herein with respect to peri-implant inflammation, osteoclastic precursor-surface interactions, and the upstream/downstream effects of surface topography on immune and progenitor cell function.

Biomaterials and Extracellular Vesicle Delivery: Current Status, Applications and Challenges.

In this review, we will discuss the current status of extracellular vesicle (EV) delivery via biopolymeric scaffolds for therapeutic applications and the challenges associated with the development of these functionalized scaffolds. EVs are cell-derived membranous structures and are involved in many physiological processes. Naïve and engineered EVs have much therapeutic potential, but proper delivery systems are required to prevent non-specific and off-target effects. Targeted and site-specific delivery using polymeric scaffolds can address these limitations. EV delivery with scaffolds has shown improvements in tissue remodeling, wound healing, bone healing, immunomodulation, and vascular performance. Thus, EV delivery via biopolymeric scaffolds is becoming an increasingly popular approach to tissue engineering. Although there are many types of natural and synthetic biopolymers, the overarching goal for many tissue engineers is to utilize biopolymers to restore defects and function as well as support host regeneration. Functionalizing biopolymers by incorporating EVs works toward this goal. Throughout this review, we will characterize extracellular vesicles, examine various biopolymers as a vehicle for EV delivery for therapeutic purposes, potential mechanisms by which EVs exert their effects, EV delivery for tissue repair and immunomodulation, and the challenges associated with the use of EVs in scaffolds.

Extracellular Vesicles From TNFα Preconditioned MSCs: Effects on Immunomodulation and Bone Regeneration.

Mesenchymal stem cells show remarkable versatility and respond to extracellular and micro environmental cues by altering their phenotype and behavior. In this regard, the MSC's immunomodulatory properties in tissue repair are well documented. The paracrine effects of MSCs in immunomodulation are, in part, attributable to their secreted extracellular vesicles (EVs). When MSCs migrate to the wound bed, they are exposed to a myriad of inflammatory signals. To understand their response to an inflammatory environment from an EV perspective, we sought to evaluate the effects of the inflammatory cytokine TNFα on MSC EV mediated immunomodulation. Our results indicate that while the physical characteristics of the EVs remain unchanged, the TNFα preconditioned MSC EVs possess enhanced immunomodulatory properties. In vitro experiments using polarized (M1 and M2) primary mouse macrophages indicated that the preconditioned MSC EVs suppressed pro-inflammatory (M1) markers such as IL-1ß and iNOS and elevated reparatory (M2) markers such as Arg1 and CD206. When evaluated in vivo in a rat calvarial defect model, the TNFα preconditioned MSC EVs reduced inflammation at 1-, 3- and 7-days post wounding resulting in the subsequent enhanced bone formation at 4- and 8-weeks post wounding possibly by modulation of oncostatin M (OSM) expression. An analysis of EV miRNA composition revealed significant changes to anti-inflammatory miRNAs in the preconditioned MSC EVs hinting at a possible role for EV derived miRNA in the enhanced immunomodulatory activity. Overall, these results indicate that MSC exposure to inflammatory signals influence the MSC EV's immunomodulatory function in the context of tissue repair. The specific function of TNFα preconditioned MSC EV miRNAs in immunomodulatory control of bone regeneration merits further investigation.

The role of complement C5a receptor in DPSC odontoblastic differentiation and in vivo reparative dentin formation.

Therapeutic dentin regeneration remains difficult to achieve, and a majority of the attention has been given to anabolic strategies to promote dentinogenesis directly, whereas, the available literature is insufficient to understand the role of inflammation and inflammatory complement system on dentinogenesis. The aim of this study is to determine the role of complement C5a receptor (C5aR) in regulating dental pulp stem cells (DPSCs) differentiation and in vivo dentin regeneration. Human DPSCs were subjected to odontogenic differentiation in osteogenic media treated with the C5aR agonist and C5aR antagonist. In vivo dentin formation was evaluated using the dentin injury/pulp-capping model of the C5a-deficient and wild-type mice. In vitro results demonstrate that C5aR inhibition caused a substantial reduction in odontogenic DPSCs differentiation markers such as DMP-1 and DSPP, while the C5aR activation increased these key odontogenic genes compared to control. A reparative dentin formation using the C5a-deficient mice shows that dentin regeneration is significantly reduced in the C5a-deficient mice. These data suggest a positive role of C5aR in the odontogenic DPSCs differentiation and tertiary/reparative dentin formation. This study addresses a novel regulatory pathway and a therapeutic approach for improving the efficiency of dentin regeneration in affected teeth.

Nanoscale hybrid implant surfaces and Osterix-mediated osseointegration.

Endosseous implant surface topography directly affects adherent cell responses following implantation. The aim of this study was to examine the impact of nanoscale topographic modification of titanium implants on Osterix gene expression since this gene has been reported as key factor for bone formation. Titanium implants with smooth and nanoscale topographies were implanted in the femurs of Osterix-Cherry mice for 1-21 days. Implant integration was evaluated using scanning electron microscopy (SEM) to evaluate cell adhesion on implant surfaces, histology, and nanotomography (NanoCT) to observe and quantify the formed bone-to-implant interface, flow cytometry to quantify of Osterix expressing cells in adjacent tissues, and real-time PCR (qPCR) to quantify the osteoinductive and osteogenic gene expression of the implant-adherent cells. SEM revealed topography-dependent adhesion of cells at early timepoints. NanoCT demonstrated greater bone formation at nanoscale implants and interfacial osteogenesis was confirmed histologically at 7 and 14 days for both smooth and nanosurface implants. Flow cytometry revealed greater numbers of Osterix positive cells in femurs implanted with nanoscale versus smooth implants. Compared to smooth surface implants, nanoscale surface adherent cells expressed higher levels of Osterix (Osx), Alkaline phosphatase (Alp), Paired related homeobox (Prx1), Dentin matrix protein 1 (Dmp1), Bone sialoprotein (Bsp), and Osteocalcin (Ocn). In conclusion, nanoscale surface implants demonstrated greater bone formation associated with higher levels of Osterix expression over the 21-day healing period with direct evidence of surface-associated gene regulation involving a nanoscale-mediated osteoinductive pathway that utilizes Osterix to direct adherent cell osteoinduction.

C5a complement receptor modulates odontogenic dental pulp stem cell differentiation under hypoxia.

AIM: Alterations in the microenvironment change the phenotypes of dental pulp stem cells (DPSCs). The role of complement component C5a in the differentiation of DPSCs is unknown, especially under oxygen-deprived conditions. The aim of this study was to determine the effect of C5a on the odontogenic differentiation of DPSCs under normoxia and hypoxia. MATERIAL AND METHODS: Human DPSCs were subjected to odontogenic differentiation in osteogenic media and treated with the C5a receptor antagonist-W54011 under normal and hypoxic conditions (2% oxygen). Immunochemistry, western blot, and PCR analysis for the various odontogenic differentiation genes/proteins were performed. RESULTS: Our results demonstrated that C5a plays a positive role in the odontogenic differentiation of DPSCs. C5a receptor inhibition resulted in a significant decrease in odontogenic differentiation genes, such as DMP1, ON, RUNX2, DSPP compared with the control. This observation was further supported by the Western blot data for DSPP and DMP1 and immunohistochemical analysis. The hypoxic condition reversed this effect. CONCLUSIONS: Our results demonstrate that C5a regulates the odontogenic DPSC differentiation under normoxia. Under hypoxia, C5a exerts a reversed function for DPSC differentiation. Taken together, we identified that C5a and oxygen levels are key initial signals during pulp inflammation to control the odontogenic differentiation of DPSCs, thereby, providing a mechanism for potential therapeutic interventions for dentin repair and vital tooth preservation.

Ti-Ions and/or Particles in Saliva Potentially Aggravate Dental Implant Corrosion.

The corrosive titanium products in peri-implant tissues are a potential risk factor for peri-implantitis. There is very limited information available on the effect of the corrosion and wear products on the dental implant corrosion. Therefore, we determined the influence of Ti-ions and Ti-particles on Ti corrosion. Eighteen commercially pure-Ti-grade-2 discs were polished to mirror-shine. Samples were divided into six groups (n = 3) as a function of electrolytes; (A) Artificial saliva (AS), (B) AS with Ti-ions (the electrolyte from group A, after corrosion), (C) AS with Ti-particles 10 ppm (D) AS with Ti-particles 20 ppm, (E) AS with Ti-ions 10 ppm, and (F) AS with Ti-ions 20 ppm. Using Tafel's method, corrosion potential (Ecorr) and current density (Icorr) were estimated from potentiodynamic curves. Electrochemical Impedance Spectroscopy (EIS) data were used to construct Nyquist and Bode plots, and an equivalent electrical circuit was used to assess the corrosion kinetics. The corroded surfaces were examined through a 3D-white-light microscope and scanning electronic microscopy. The data demonstrated that the concentration of Ti-ions and corrosion rate (Icorr) are strongly correlated (r = 0.997, p = 0.046). This study indicated that high Ti-ion concentration potentially aggravates corrosion. Under such a severe corrosion environment, there is a potential risk of increased implant associated adverse tissue reactions.

Testing for COVID-19 in dental offices: Mechanism of action, application, and interpretation of laboratory and point-of-care screening tests.

BACKGROUND: The dental office potentially possesses all transmission risk factors for severe acute respiratory syndrome coronavirus 2. Anticipating the future widespread use of COVID-19 testing in dental offices, the authors wrote this article as a proactive effort to provide dental health care providers with current and necessary information surrounding the topic. METHODS: The authors consulted all relevant and current guidelines from the Centers for Disease Control and Prevention and the US Food and Drug Administration, as well as online resources and review articles. RESULTS: Routine COVID-19 screening and triage protocols are unable to detect all infected people. With the advancements in diagnostic tools and techniques, COVID-19 testing at home or in the dental office may provide dentists with the ability to evaluate the disease status of their patients. At-home or point-of-care (POC) tests, providing results within minutes of being administered, would allow for appropriate measures and rapid decisions about dental patients' care process. In this review, the authors provide information about available laboratory and POC COVID-19 screening methods and identify and elaborate on the options available for use by dentists as well as the regulatory requirements of test administration. CONCLUSIONS: Dentists need to be familiar with COVID-19 POC testing options. In addition to contributing to public health, such tests may deliver rapid, accurate, and actionable results to clinical and infection control teams to enhance the safe patient flow in dental practices. PRACTICAL IMPLICATIONS: Oral health care must continue to offer safety in this or any future pandemics. Testing for severe acute respiratory syndrome coronavirus 2 at the POC offers a control mechanism contributing to and enhancing the real and perceived safety of care in the dental office setting.

Characteristics and Detection Rate of SARS-CoV-2 in Alternative Sites and Specimens Pertaining to Dental Practice: An Evidence Summary.

Knowledge about the detection potential and detection rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various body fluids and sites is important for dentists since they, directly or indirectly, deal with many of these fluids/sites in their daily practices. In this study, we attempt to review the latest evidence and meta-analysis studies regarding the detection rate of SARS-CoV-2 in different body specimens and sites as well as the characteristics of these sample. The presence/detection of SARS-CoV-2 viral biomolecules (nucleic acid, antigens, antibody) in different clinical specimens depends greatly on the specimen type and timing of collection. These specimens/sites include nasopharynx, oropharynx, nose, saliva, sputum, bronchoalveolar lavage, stool, urine, ocular fluid, serum, plasma and whole blood. The relative detection rate of SARS-CoV-2 viral biomolecules in each of these specimens/sites is reviewed in detail within the text. The infectious potential of these specimens depends mainly on the time of specimen collection and the presence of live replicating viral particles.

Computer simulation of the SARS-CoV-2 contamination risk in a large dental clinic.

COVID-19, caused by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus, has been rapidly spreading worldwide since December 2019, causing a public health crisis. Recent studies showed SARS-CoV-2's ability to infect humans via airborne routes. These motivated the study of aerosol and airborne droplet transmission in a variety of settings. This study performs a large-scale numerical simulation of a real-world dentistry clinic that contains aerosol-generating procedures. The simulation tracks the dispersion of evaporating droplets emitted during ultrasonic dental scaling procedures. The simulation considers 25 patient treatment cubicles in an open plan dentistry clinic. The droplets are modeled as having a volatile (evaporating) and nonvolatile fraction composed of virions, saliva, and impurities from the irrigant water supply. The simulated clinic's boundary and flow conditions are validated against experimental measurements of the real clinic. The results evaluate the behavior of large droplets and aerosols. We investigate droplet residence time and travel distance for different droplet diameters, surface contamination due to droplet settling and deposition, airborne aerosol mass concentration, and the quantity of droplets that escape through ventilation. The simulation results raise concerns due to the aerosols' long residence times (averaging up to 7.31 min) and travel distances (averaging up to 24.45 m) that exceed social distancing guidelines. Finally, the results show that contamination extends beyond the immediate patient treatment areas, requiring additional surface disinfection in the clinic. The results presented in this research may be used to establish safer dental clinic operating procedures, especially if paired with future supplementary material concerning the aerosol viral load generated by ultrasonic scaling and the viral load thresholds required to infect humans.

3D Encapsulation and tethering of functionally engineered extracellular vesicles to hydrogels.

Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) in their naïve and engineered forms have emerged as potential alternatives to stem cell therapy. While they have a defined therapeutic potential, the spatial and temporal control of their activity in vivo remains a challenge. The objective of this study was to devise a methodology to encapsulate EVs in 3D hydrogels for prolonged delivery. To achieve this, we have leveraged the MSC EV interactions with ECM proteins and their derivative peptides. Using osteoinductive functionally engineered EVs (FEEs) derived from MSCs, we show that FEEs bind to mimetic peptides from collagen (DGEA, GFPGER) and fibronectin (RGD). In in vitro experiments, photocrosslinkable alginate hydrogels containing RGD were able to encapsulate, tether and retain the FEEs over a period of 7 days while maintaining the structural integrity and osteoinductive functionality of the EVs. When employed in a calvarial defect model in vivo, alginate-RGD hydrogels containing the FEEs enhanced bone regeneration by a factor of 4 compared to controls lacking FEEs and by a factor of 2 compared to controls lacking the tethering peptide. These results show that EVs can be tethered to biomaterials to promote bone repair and the importance of prolonged delivery in vivo. Results also provide a prelude to the possible use of this technology for controlled delivery of EVs for other regenerative medicine applications. STATEMENT OF SIGNIFICANCE: The beneficial effects of human MSC (HMSC) therapy are attributable to paracrine effects of the HMSC derived EVs. While EV engineering has the potential to impact several fields of regenerative medicine, targeted delivery of the engineered EVs with spatial and temporal control is necessary to prevent off-target effects and enhance tissue specificity. Here, we have leveraged the interactions of MSC EVs with ECM proteins to develop a tethering system that can be utilized to prolong EV delivery in vivo while maintaining the structural and functional integrity of the EVs. Our work has provided a tunable platform for EV delivery that we envision can be formulated as an injectable material or a bulk hydrogel suitable for regenerative medicine applications.

The importance of cellular and exosomal miRNAs in mesenchymal stem cell osteoblastic differentiation.

The differentiation of osteoblasts is under complex regulation that includes autocrine and paracrine signaling from MSCs. Exosomes are important components of the MSC secretome and their cargo contains numerous miRNAs. In this study, the importance of MSC miRNAs in modulation of osteoblastic differentiation was examined by global reduction of miRNA biosynthesis in Dicer knock down hMSCs. We additionally impaired hMSC responses to miRNAs by knockdown of Argonaute 2 expression. Knockdown of Dicer and Argonaute 2 both reduced osteoblastic differentiation of hMSCs. This was observed at the levels of hMSC culture mineralization and osteoblastic gene expression. The treatment of Dicer deficient hMSCs with wild type hMSC exosomes effectively recovered the impaired osteoblastic differentiation. Dicer knockdown reduced the quantity and diversity of miRNAs present in hMSC exosomes. miRSeq data and KEGG analysis implicated the miRNA-dependent effects on multiple osteoinductive pathways in Dicer deficient cells, including the Hippo signaling and TGF-beta signaling pathways. Treatment of hMSCs with mimics of miRNAs significantly downregulated in Dicer knockdown cells recovered functions of exosome-mediated signaling in hMSCs. These results indicate that hMSC exosomes exert miRNA-dependent control that contributes to osteoblastic differentiation.

A 5-Year Esthetic RCT Assessment of Anterior Maxillary Single-Tooth Implants with Different Abutment Interfaces.

PURPOSE: This study sought to define the tissue responses at different implant-abutment interfaces by studying bone and peri-implant mucosal changes using a 5-year prospective randomized clinical trial design study. The conus interface was compared with the flat-to-flat interface and platform-switched implant-abutment systems. MATERIALS AND METHODS: One hundred forty-one subjects were recruited and randomized to the three treatment groups according to defined inclusion and exclusion criteria. Following implant placement and immediate provisionalization in healed alveolar ridges, clinical, photographic, and radiographic parameters were measured at 6 months and annually for 5 years. The calculated changes in marginal bone levels, peri-implant mucosal zenith location, papillae lengths, and peri-implant Plaque Index and bleeding on probing were statistically compared. RESULTS: Forty-eight conus interface implants, 49 flat-to-flat interface implants, and 44 platform-switched implants were placed in 141 subjects. Six platform-switched interface and eight flatto- flat interface implants failed, most of them within 3 months. After 5 years, 33 conical interface, 28 flat-to-flat interface, and 27 platform-switched interface implants remained for evaluation. Calculation of marginal bone level change showed a mean marginal bone loss of -0.16 ± 0.45 (-1.55 to 0.65), -0.92 ± 0.70 (-2.90 to 0.20), and -0.81 ± 1.06 (-3.35 to 1.35) mm for conical interface, flat-to-flat interface, and platform-switched interface implants, respectively (P < .0005). The peri-implant mucosal zenith changes were minimal for all three interface designs (0.10 mm and +0.08 mm, P > .60). Only 16% to 19% of the surfaces had presence of bleeding on probing, with no significant differences (P > .81) between groups. Interproximal tissue changes were positive and similar among the implant interface designs. CONCLUSION: Over 5 years, the immediate provisionalization protocol resulted in stable peri-implant mucosal responses for all three interfaces. Compared with the flat-to-flat and platform-switched interfaces, the conical interface implants demonstrated significantly less early marginal bone loss. The relationship of marginal bone responses and mucosal responses requires further experimental consideration.

A digital approach to robust and esthetic implant overdenture construction.

OBJECTIVE: Overdenture therapy is an important option for implant rehabilitation. However, numerous reports suggest that mechanical/technical complications and failures can limit therapeutic success. The goal of this report is to illustrate a digital approach to design and construction of a robust overdenture with high-esthetic value. MATERIALS AND METHODS: Beginning with new denture design to establish esthetic parameters, 3D modeling of a metal framework and the denture teeth are completed in a connected manner. This enables connection of rapidly printed, prototype dentition that is attached directly to the framework without intervening wax or acrylic components. Following evaluation of the dentition and required adjustments, the final dentition is milled from resin and processed to the selective laser sintered framework. RESULTS: The advantages of the digital workflow include the control of dimensions and strength of the framework, the esthetic relationship of the framework to the dentition and the facilitation of esthetic try-in of the dentition. CONCLUSION: Enhancing a robust overdenture can be readily achieved using a digital workflow. CLINICAL SIGNIFICANCE: The use of digital technology enables the clinical team to plan and produce prostheses with dimensions and contours that support long-term function and esthetics. The clinical chair time can be potentially reduced by use of digital design that facilitates try-in and reduces major errors by improved communication between the patient, dentist, and technician.

Reopening dentistry after COVID-19: Complete suppression of aerosolization in dental procedures by viscoelastic Medusa Gorgo.

The aerosol transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has impacted the delivery of health care and essentially stopped the provision of medical and dental therapies. Dentistry uses rotary, ultrasonic, and laser-based instruments that produce water-based aerosols in the daily, routine treatment of patients. Abundant aerosols are generated, which reach health care workers and other patients. Viruses, including SARS-CoV-2 virus and related coronavirus disease (COVID-19) pandemic, continued expansion throughout the USA and the world. The virus is spread by both droplet (visible drops) and aerosol (practically invisible drops) transmission. The generation of aerosols in dentistry-an unavoidable part of most dental treatments-creates a high-risk situation. The US Centers for Disease Control and The Occupational Safety and Health Administration consider dental procedures to be of "highest risk" in the potential spreading of SARS-CoV-2 and other respiratory viruses. There are several ways to reduce or eliminate the virus: (i) cease or postpone dentistry (public and personal health risk), (ii) screen patients immediately prior to dental treatment (by appropriate testing, if any), (iii) block/remove the virus containing aerosol by engineering controls together with stringent personal protective equipment use. The present work takes a novel, fourth approach. By altering the physical response of water to the rotary or ultrasonic forces that are used in dentistry, the generation of aerosol particles and the distance any aerosol may spread beyond the point of generation can be markedly suppressed or completely eliminated in comparison to water for both the ultrasonic scaler and dental handpiece.