A quantitative evaluation of the impact of vaccine roll-out rate and coverage on reducing deaths: insights from the first 2 years of COVID-19 epidemic in Iran.

BACKGROUND: Vaccination has played a pivotal role in reducing the burden of COVID-19. Despite numerous studies highlighting its benefits in reducing the risk of severe disease and death, we still lack a quantitative understanding of how varying vaccination roll-out rates influence COVID-19 mortality. METHODS: We developed a framework for estimating the number of avertable COVID-19 deaths (ACDs) by vaccination in Iran. To achieve this, we compared Iran's vaccination roll-out rates with those of eight model countries that predominantly used inactivated virus vaccines. We calculated net differences in the number of fully vaccinated individuals under counterfactual scenarios where Iran's per-capita roll-out rate was replaced with that of the model countries. This, in turn, enabled us to determine age specific ACDs for the Iranian population under counterfactual scenarios where number of COVID-19 deaths are estimated using all-cause mortality data. These estimates covered the period from the start of 2020 to 20 April 2022. RESULTS: We found that while Iran would have had an approximately similar number of fully vaccinated individuals under counterfactual roll-out rates based on Bangladesh, Nepal, Sri Lanka, and Turkey (~ 65-70%), adopting Turkey's roll-out rates could have averted 50,000 (95% confidence interval: 38,100-53,500) additional deaths, while following Bangladesh's rates may have resulted in 52,800 (17,400-189,500) more fatalities in Iran. Surprisingly, mimicking Argentina's slower roll-out led to only 12,600 (10,400-13,300) fewer deaths, despite a higher counterfactual percentage of fully vaccinated individuals (~ 79%). Emulating Montenegro or Bolivia, with faster per capita roll-out rates and approximately 50% counterfactual full vaccination, could have prevented more deaths in older age groups, especially during the early waves. Finally, replicating Bahrain's model as an upper-bound benchmark, Iran could have averted 75,300 (56,000-83,000) deaths, primarily in the > 50 age groups. CONCLUSIONS: Our analysis revealed that faster roll-outs were consistently associated with higher numbers of averted deaths, even in scenarios with lower overall coverage. This study offers valuable insights into future decision-making regarding infectious disease epidemic management through vaccination strategies. It accomplishes this by comparing various countries' relative performance in terms of timing, pace, and vaccination coverage, ultimately contributing to the prevention of COVID-19-related deaths.

Mesoporous Core-Cone Silica Nanoparticles Can Deliver miRNA-26a to Macrophages to Exert Immunomodulatory Effects on Osteogenesis In Vitro.

Nanoparticles can play valuable roles in delivering nucleic acids, including microRNAs (miRNA), which are small, non-coding RNA segments. In this way, nanoparticles may exert post-transcriptional regulatory influences on various inflammatory conditions and bone disorders. This study used biocompatible, core-cone-structured, mesoporous silica nanoparticles (MSN-CC) to deliver miRNA-26a to macrophages in order to influence osteogenesis in vitro. The loaded nanoparticles (MSN-CC-miRNA-26) showed low-level toxicity towards macrophages (RAW 264.7 cells) and were internalized efficiently, causing the reduced expression of pro-inflammatory cytokines, as seen via real-time PCR and cytokine immunoassays. The conditioned macrophages created a favorable osteoimmune environment for MC3T3-E1 preosteoblasts, driving osteogenic differentiation with enhanced osteogenic marker expression, alkaline phosphatase (ALP) production, extracellular matrix formation, and calcium deposition. An indirect co-culture system revealed that direct osteogenic induction and immunomodulation by MSN-CC-miRNA-26a synergistically increased bone production due to the crosstalk between MSN-CC-miRNA-26a-conditioned macrophages and MSN-CC-miRNA-26a-treated preosteoblasts. These findings demonstrate the value of nanoparticle delivery of miR-NA-26a using MSN-CC for suppressing the production of pro-inflammatory cytokines with macrophages and for driving osteogenic differentiation in preosteoblasts via osteoimmune modulation.

Dentinal Tubule Penetrability and Bond Strength of Two Novel Calcium Silicate-Based Root Canal Sealers.

BACKGROUND: Once the chemo-mechanical preparation of root canals is finished, achieving a complete seal of the root canal system becomes crucial in determining the long-term success of endodontic treatment. The important goals of root canal obturation are to minimize leakage and achieve an adequate seal. Thus, a material that possesses satisfactory mechanical characteristics, is biocompatible, and has the ability to penetrate the dentine tubules adequately is needed. AIM: This study aimed to compare the penetrability and bond strength between two calcium silicate-based sealers and an epoxy resin-based sealer, as well as examine the relationship between penetrability and bond strength for the different sealers. METHOD AND MATERIALS: Thirty-nine recently extracted single-rooted human premolar teeth were instrumented and divided evenly into three groups (n = 13), according to the sealer used for obturation: AH Plus Jet, EndoSequence, and AH Plus Bioceramic Sealer. Three teeth (30 slices) were randomly selected out of each for analysis using confocal laser scanning microscopy to assess penetrability. The remaining ten teeth (90 slices) in each group were subject to push-out tests using a universal testing machine. All teeth were sectioned into nine transverse slices of 0.9 mm thickness for their respective tests (apical, middle, coronal). RESULTS: AH Plus Jet exhibited significantly lower penetrability and significantly higher bond strength compared to EndoSequence BC sealer (p = 0.002) and AH Plus Bioceramic Sealer (p = 0.006). There was no significant difference between EndoSequence BC sealer and AH Plus Bioceramic Sealer in terms of either penetrability or bond strength. No correlation was found between penetrability and bond strength. CONCLUSIONS: Within the limitation of this study and regardless of the location in the canal, the bioceramic based root canal sealers appeared to perform better than the epoxy resin-based sealer in terms of dentinal penetration rate. Further studies are required to compare other biomechanical properties of bioceramic sealers including setting characteristics and bacterial leakage.

Immunomodulatory Effects of Endodontic Sealers: A Systematic Review.

Inflammation is a crucial step prior to healing, and the regulatory effects of endodontic materials on the immune response can influence tissue repair. This review aimed to answer whether endodontic sealers can modulate the immune cells and inflammation. An electronic search in Scopus, Web of Science, PubMed, and Google Scholar databases were performed. This systematic review was mainly based on PRISMA guidelines, and the risk of bias was evaluated by SYRCLEs and the Modified CONSORT checklist for in vivo and in vitro studies, respectively. In total, 28 articles: 22 in vitro studies, and six in vivo studies were included in this systematic review. AH Plus and AH 26 can down-regulate iNOS mRNA, while S-PRG sealers can down-regulate p65 of NF-κB pathways to inhibit the production of TNF-α, IL-1, and IL-6. In vitro and in vivo studies suggested that various endodontic sealers exhibited immunomodulatory impact in macrophages polarization and inflammatory cytokine production, which could promote healing, tissue repair, and inhibit inflammation. Since the paradigm change from immune inert biomaterials to bioactive materials, endodontic materials, particularly sealers, are required to have modulatory effects in clinical conditions. New generations of endodontic sealers could hamper detrimental inflammatory responses and maintain periodontal tissue, which represent a breakthrough in biocompatibility and functionality of endodontic biomaterials.

A Comparative Study of Mesoporous Silica and Mesoporous Bioactive Glass Nanoparticles as Non-Viral MicroRNA Vectors for Osteogenesis.

Micro-ribonucleic acid (miRNA)-based therapies show advantages for bone regeneration but need efficient intracellular delivery methods. Inorganic nanoparticles such as mesoporous bioactive glass nanoparticles (MBGN) and mesoporous silica nanoparticles (MSN) have received growing interest in the intracellular delivery of nucleic acids. This study explores the capacity of MBGN and MSN for delivering miRNA to bone marrow mesenchymal stem cells (BMSC) for bone regenerative purposes, with a focus on comparing the two in terms of cell viability, transfection efficiency, and osteogenic actions. Spherical MBGN and MSN with a particle size of ~200 nm and small-sized mesopores were prepared using the sol-gel method, and then the surface was modified with polyethyleneimine for miRNA loading and delivery. The results showed miRNA can be loaded into both nanoparticles within 2 h and was released sustainedly for up to 3 days. Confocal laser scanning microscopy and flow cytometry analysis indicated a high transfection efficiency (>64%) of both nanoparticles without statistical difference. Compared with MSN, MBGN showed stronger activation of alkaline phosphatase and activation of osteocalcin genes. This translated to a greater osteogenic effect of MBGN on BMSC, with Alizarin red staining showing greater mineralization compared with the MSN group. These findings show the potential for MBGN to be used in bone tissue engineering.

Nanotechnology for the management of COVID-19 during the pandemic and in the post-pandemic era.

Following the global COVID-19 pandemic, nanotechnology has been at the forefront of research efforts and enables the fast development of diagnostic tools, vaccines and antiviral treatment for this novel virus (SARS-CoV-2). In this review, we first summarize nanotechnology with regard to the detection of SARS-CoV-2, including nanoparticle-based techniques such as rapid antigen testing, and nanopore-based sequencing and sensing techniques. Then we investigate nanotechnology as it applies to the development of COVID-19 vaccines and anti-SARS-CoV-2 nanomaterials. We also highlight nanotechnology for the post-pandemic era, by providing tools for the battle with SARS-CoV-2 variants and for enhancing the global distribution of vaccines. Nanotechnology not only contributes to the management of the ongoing COVID-19 pandemic but also provides platforms for the prevention, rapid diagnosis, vaccines and antiviral drugs of possible future virus outbreaks.

A Clinical Risk Assessment of a 3D-Printed Patient-Specific Scaffold by Failure Modes and Effects Analysis.

This study aims to carry out a risk assessment to identify and rectify potential clinical risks of a 3D-printed patient-specific scaffold for large-volume alveolar bone regeneration. A survey was used to assess clinicians' perceptions regarding the use of scaffolds in the treatment of alveolar defects and conduct a clinical risk assessment of the developed scaffold using the Failure Modes and Effects Analysis (FMEA) framework. The response rate was 69.4% with a total of 41 responses received. Two particular failure modes were identified as a high priority through the clinical risk assessment conducted. The highest mean Risk Priority Number was obtained by "failure of healing due to patient risk factors" (45.7 ± 27.7), followed by "insufficient soft tissue area" (37.8 ± 24.1). Despite the rapid developments, finding a scaffold that is both biodegradable and tailored to the patient's specific defect in cases of large-volume bone regeneration is still challenging for clinicians. Our results indicate a positive perception of clinicians towards this novel scaffold. The FMEA clinical risk assessment has revealed two failure modes that should be prioritized for risk mitigation (safe clinical translation). These findings are important for the safe transition to in-human trials and subsequent clinical use.

A critical analysis of research methods and experimental models to study biocompatibility of endodontic materials.

Materials used for endodontics and with direct contact to tissues have a wide range of indications, from vital pulpal treatments to root filling materials and those used in endodontic surgery. In principle, interaction with dental materials may result in damage to tissues locally or systemically. Thus, a great variety of test methods are applied to evaluate a materials' potential risk of adverse biological effects to ensure their biocompatibility before commercialization. However, the results of biocompatibility evaluations are dependent on not only the tested materials but also the test methods due to the diversity of these effects and numerous variables involved. In addition, diverse biological effects require equally diverse assessments on a structured and planned approach. Such a structured assessment of the materials consists of four phases: general toxicity, local tissue irritation, pre-clinical tests and clinical evaluations. Various types of screening assays are available; it is imperative to understand their advantages and limitations to recognize their appropriateness and for an accurate interpretation of their results. Recent scientific advances are rapidly introducing new materials to endodontics including nanomaterials, gene therapy and tissue engineering biomaterials. These new modalities open a new era to restore and regenerate dental tissues; however, all these new technologies can also present new hazards to patients. Before any clinical usage, new materials must be proven to be safe and not hazardous to health. Certain international standards exist for safety evaluation of dental materials (ISO 10993 series, ISO 7405 and ISO 14155-1), but researchers often fail to follow these standards due to lack of access to standards, limitation of the guidelines and complexity of new experimental methods, which may cause technical errors. Moreover, many laboratories have developed their testing strategy for biocompatibility, which makes any comparison between findings more difficult. The purpose of this review was to discuss the concept of biocompatibility, structured test programmes and international standards for testing the biocompatibility of endodontic material biocompatibility. The text will further detail current test methods for evaluating the biocompatibility of endodontic materials, and their advantages and limitations.

Modulating Osteoimmune Responses by Mesoporous Silica Nanoparticles.

The immune response plays an important role in biomaterial-mediated osteogenesis. Nanomaterials may influence immune responses and thereby alter bone regeneration. Mesoporous silica nanoparticles (MSNs) have received much attention for drug delivery and bone regeneration. Recently, immunomodulatory effects of MSNs on osteogenesis have been reported. In this Review, we summarize the osteoimmunomodulation of MSNs, including the effects of MSN characteristics on immune cells and osteogenesis. Impacts of MSNs on immune cells vary according to nanoparticle properties, including surface topography and charge, particle size, and ion release. MSNs with suitable doses can inhibit inflammation and create an immune microenvironment beneficial for bone regeneration by activating immune cells and stimulating cytokine release. Further work is needed to explore and clarify the underlying mechanisms, including crosstalk between various types of immune cells and how to design MSNs to create a suitable immune environment for osteogenesis.

Microbial Decontamination and Antibacterial Activity of Nanostructured Titanium Dental Implants: A Narrative Review.

Peri-implantitis is the major cause of the failure of dental implants. Since dental implants have become one of the main therapies for teeth loss, the number of patients with peri-implant diseases has been rising. Like the periodontal diseases that affect the supporting tissues of the teeth, peri-implant diseases are also associated with the formation of dental plaque biofilm, and resulting inflammation and destruction of the gingival tissues and bone. Treatments for peri-implantitis are focused on reducing the bacterial load in the pocket around the implant, and in decontaminating surfaces once bacteria have been detached. Recently, nanoengineered titanium dental implants have been introduced to improve osteointegration and provide an osteoconductive surface; however, the increased surface roughness raises issues of biofilm formation and more challenging decontamination of the implant surface. This paper reviews treatment modalities that are carried out to eliminate bacterial biofilms and slow their regrowth in terms of their advantages and disadvantages when used on titanium dental implant surfaces with nanoscale features. Such decontamination methods include physical debridement, chemo-mechanical treatments, laser ablation and photodynamic therapy, and electrochemical processes. There is a consensus that the efficient removal of the biofilm supplemented by chemical debridement and full access to the pocket is essential for treating peri-implantitis in clinical settings. Moreover, there is the potential to create ideal nano-modified titanium implants which exert antimicrobial actions and inhibit biofilm formation. Methods to achieve this include structural and surface changes via chemical and physical processes that alter the surface morphology and confer antibacterial properties. These have shown promise in preclinical investigations.

Specialized pro-resolving lipid mediators in endodontics: a narrative review.

Endodontics is the branch of dentistry concerned with the morphology, physiology, and pathology of the human dental pulp and periradicular tissues. Human dental pulp is a highly dynamic tissue equipped with a network of resident immunocompetent cells that play major roles in the defense against pathogens and during tissue injury. However, the efficiency of these mechanisms during dental pulp inflammation (pulpitis) varies due to anatomical and physiological restrictions. Uncontrolled, excessive, or unresolved inflammation can lead to pulp tissue necrosis and subsequent bone infections called apical periodontitis. In most cases, pulpitis treatment consists of total pulp removal. Although this strategy has a good success rate, this treatment has some drawbacks (lack of defense mechanisms, loss of healing capacities, incomplete formation of the root in young patients). In a sizeable number of clinical situations, the decision to perform pulp extirpation and endodontic treatment is justifiable by the lack of therapeutic tools that could otherwise limit the immune/inflammatory process. In the past few decades, many studies have demonstrated that the resolution of acute inflammation is necessary to avoid the development of chronic inflammation and to promote repair or regeneration. This active process is orchestrated by Specialized Pro-resolving lipid Mediators (SPMs), including lipoxins, resolvins, protectins and maresins. Interestingly, SPMs do not have direct anti-inflammatory effects by inhibiting or directly blocking this process but can actively reduce neutrophil infiltration into inflamed tissues, enhance efferocytosis and bacterial phagocytosis by monocytes and macrophages and simultaneously inhibit inflammatory cytokine production. Experimental clinical application of SPMs has shown promising result in a wide range of inflammatory diseases, such as renal fibrosis, cerebral ischemia, marginal periodontitis, and cancer; the potential of SPMs in endodontic therapy has recently been explored. In this review, our objective was to analyze the involvement and potential use of SPMs in endodontic therapies with an emphasis on SPM delivery systems to effectively administer SPMs into the dental pulp space.

Efficient transfection and long-term stability of rno-miRNA-26a-5p for osteogenic differentiation by large pore sized mesoporous silica nanoparticles.

MicroRNA (miRNA) based therapy for bone repair has shown promising results for regulating stem cell proliferation and differentiation, an efficient and stable vector for delivery of microRNA delivery is needed. The present study explored the stability and functionality of lyophilized mesoporous silica nanoparticles with core-cone structure and coated with polyethylenimine (MSN-CC-PEI) as a system for delivering Rattus norvegicus (rno)-miRNA-26a-5p into rat marrow mesenchymal cells (rBMSCs) to promote their osteogenic differentiation. We assessed the cellular uptake and transfection efficiency of nanoparticles loaded with labelled miRNA using confocal laser scanning microscopy and flow cytometry, and the cell viability using the MTT assay. The expression levels of osteogenic genes after one and two weeks were analysed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Extracellular matrix deposition and mineralization at 3 weeks were evaluated using Picro Sirius red and Alizarin red staining. We also assessed the performance of the delivery system after long term storage, by freeze drying rno-miRNA-26a-5p@MSN-CC-PEI with 5% trehalose and keeping them at -30 °C for 3 and 6 months. Osteogenic differentiation, matrix deposition, and mineralization were all significantly increased by rno-miRNA-26a-5p. In addition, this enhancement was not significantly altered by lyophilization and storage. Overall, these findings support the concept of MSN-CC-PEI as a delivery system for gene therapy. The complex of rno-miRNA-26a-5p@MSN-CC-PEI could efficiently transfect rBMSCs and enhance their osteogenic differentiation. In addition, the lyophilized complexes remain functional after 6 months of storage.

Impact of photobiomodulation using four diode laser wavelengths of on cationic liposome gene transfection into pre-osteoblast cells.

Gene therapy can be an effective treatment modality for some severe genetic diseases. Despite efforts to improve their performance, non-viral gene delivery methods remain inefficient and costly. As an alternative to viral vectors, cationic liposomes have a good safety profile and low immunogenicity, but relatively low transfection efficiency. They may also be toxic to cells at high concentrations. Given these challenges, the present study explored the impact of photobiomodulation (PBM) on cationic liposome plasmid DNA transfection in terms of its efficiency and toxicity, using Lipofectamine 2000 to carry green fluorescent protein (GFP) encoding plasmid DNA, with the pre-osteoblast MC3T3-E1 cell line as the target. Cultures were irradiated using diode lasers (445, 685, 810, or 970 nm) at 200 mW using pulsed mode (50 Hz), with a power density of 104.64 mW/cm2, and irradiance from 6 to 18 joules. To determine transfection efficiency, expression of GFP was assessed using confocal laser scanning microscopy and flow cytometry. Cell viability was evaluated using the MTT assay. PBM using 810 nm and 970 nm lasers significantly enhanced transfection efficiency for GFP, indicating more efficient uptake of plasmid DNA. Conversely, laser irradiation at 445 nm and 685 nm wavelengths reduced the GFP transfection efficiency. Treatment using 685, 810, and 970 nm lasers at 12 J maintained cell viability and prevented toxicity of cationic liposomes. Overall, these findings support the concept that PBM using near infrared laser wavelengths can enhance transfection efficiency and support cell viability when cationic liposomes are used as the vector in gene therapy.

Laser-assisted nucleic acid delivery: A systematic review.

Gene therapy has become an effective treatment modality for some conditions. Laser light may augment or enhance gene therapy through photomechanical, photothermal, and photochemical. This review examined the evidence base for laser therapy to enhance nucleic acid transfection in mammalian cells. An electronic search of MEDLINE, Scopus, EMBASE, Web of Science, and Google Scholar was performed, covering all available years. The preferred reporting items for systematic reviews and meta-analyses guideline for systematic reviews was used for designing the study and analyzing the results. In total, 49 studies of laser irradiation for nucleic acid delivery were included. Key approaches were optoporation, photomechanical gene transfection, and photochemical internalization. Optoporation is better suited to cells in culture, photomechanical and photochemical approaches appear well suited to in vivo use. Additional studies explored the impact of photothermal for enhancing gene transfection. Each approach has merits and limitations. Augmenting nucleic acid delivery using laser irradiation is a promising method for improving gene therapy. Laser protocols can be non-invasive because of the penetration of desirable wavelengths of light, but it depends on various parameters such as power density, treatment duration, irradiation mode, etc. The current protocols show low efficiency, and there is a need for further work to optimize irradiation parameters.

Biomedical application of mesoporous silica nanoparticles as delivery systems: a biological safety perspective.

The application of mesoporous silica nanoparticles (MSNs) as drug delivery systems to deliver drugs, proteins, and genes has expanded considerably in recent years, using in vitro and animal studies. For future translation to clinical applications, the biological safety aspects of MSNs must be considered carefully. This paper reviews the biosafety of MSNs, examining key issues such as biocompatibility, effects on immune cells and erythrocytes, biodistribution, biodegradation and clearance, and how these vary depending on the effects of the physical and chemical properties of MSNs such as particle size, porosity, morphology, surface charge, and chemical modifications. The future use of MSNs as a delivery system must extend beyond what has been learnt thus far using rodent animal models to encompass larger animals.

Photobiomodulation in Temporomandibular Disorders.

Objective: This systematic review aimed to comprehensively review all available documents regarding photobiomodulation therapy (PBMT) application in temporomandibular disorder (TMD) patients and to suggest an evidence-based protocol for therapeutic PBM administration for these patients. Background data: The existence of temporomandibular joint and/or pain and dysfunction in masticatory muscles is characterized in TMDs. PBMT is, due to its impact on biological processes, especially inflammation, considered as an adjuvant treatment modality in TMD cases. Materials and methods: All original articles related to PBMT for TMDs in EMBASE, MEDLINE (NCBI PubMed and PMC), Cochrane library, Scopus, Web of Science, and Google Scholar were reviewed until December 2018. Results: The energy density ranging from 0.75 to 112.5 J/cm2 with 0.9-500 mW power was found to be a window protocol for light application. The best results for pain relief and mandibular movement enhancement were reported after application of GaAlAs diode laser, 800-900 nm, 100-500 mW, and <10 J/cm2, twice a week for 30 days on trigger points. The session of light applications varied from 1 to 20. Conclusions: Although most articles showed that PBMT is effective in reducing pain and contributed to functional enhancement in TMD patients, the heterogenic parameters that have been reported in various studies made the standardization of PBMT complicated. However, such evidence-based consensus can be beneficial for both future research and for clinical applications.

Photobiomodulation in Oral Surgery: A Review.

Objective: This article presents a review of current data on the applications of photobiomodulation (PBM) in the field of oral and maxillofacial surgery (OMFS), to guide future research. Background data: Photobiomodulation therapy (PBMT) has been reported to be effective for various postoperative conditions, including pain relief, improvement of mastication, neurosensory recovery, and wound healing. There is a need for identifying the therapeutic irradiation windows for these conditions, based upon the available literature. Materials and methods: All original articles related to PBM for oral surgery in MEDLINE (NCBI PubMed and PMC), EMBASE, Scopus, Cochrane library, Web of Science, and Google Scholar were reviewed until December 2018. Results: Forty-six clinical trials were included in this study. These trials were categorized into three different types of PBM applications. After reviewing all these studies, the most effective physical properties for PBM pain reduction after tooth extraction were as follows: wavelength 650-980 nm; power 4-300 mW; and energy density 3-85.7 J/cm2. PBMT at 660-910 nm with 4-500 mW power and 2-480 J/cm2 energy density was effective for decreasing facial swelling. At the same wavelength and power range with 4-106 J/cm2 energy density, PBM was effective for alleviating trismus after tooth extraction. Conclusions: Most papers suggested that PBM seemed to be effective in reducing pain, swelling, and trismus after third molar tooth extraction, neurosensory and nerve recovery after mandibular ramus osteotomy. The heterogeneity of the standardization regarding the parameters of laser calls for caution in interpretation of these results. However, this evidence-based review regarding the best protocols for OMFS applications can be beneficial for both future research and clinical applications.

MicroRNAs Involved in the Regulation of Angiogenesis in Bone Regeneration.

MicroRNAs (miRNAs) as a newly founded and thriving non-coding endogenous class of molecules which regulate many cellular pathways after transcription have been extensively investigated in regenerative medicine. In this systematic review, we sought to analyze miRNAs-mediated therapeutic approaches for influencing angiogenesis in bone tissue/bone regeneration. An electronic search in MEDLINE, Scopus, EMBASE, Cochrane library, web of science, and google scholar with no time limit were done on English publications. All types of original articles which a miRNA for angiogenesis in bone regeneration were included in our review. In the process of reviewing, we used PRISMA guideline and, SYRCLE's and science in risk assessment and policy tools for analyzing risk of bias. Among 751 initial retrieved records, 16 studies met the inclusion criteria and were fully assessed in this review. 275 miRNAs, one miRNA 195~497 cluster, and one Cysteine-rich 61 short hairpin RNA were differentially expressed during bone regeneration with 24 predicted targets reported in these studies. Among these miRNAs, miRNA-7b, -9, -21, -26a, -27a, -210, -378, -195~497 cluster, -378 and -675 positively promoted both angiogenesis and osteogenesis, whereas miRNA-10a, -222 and -494 inhibited both processes. The most common target was vasculoendothelial growth factor-signaling pathway. Recent evidence has demonstrated that miRNAs actively participated in angio-osteogenic coupling that can improve their therapeutic potentials for the treatment of bone-related diseases and bone regeneration. However, there is still need for further research to unravel the exact mechanisms.

Molecular impacts of photobiomodulation on bone regeneration: A systematic review.

Photobiomodulation (PBM) encompasses a light application aimed to increase healing process, tissue regeneration, and reducing inflammation and pain. PBM is specifically aimed to modify the expression of cellular molecules; however, PBM impacts on cellular and molecular pathways especially in bone regenerative medicine have been investigated in scattered different studies. The purpose of the current study is to systematically review evidence on molecular impact of PBM on bone regeneration. A comprehensive electronic search in Medline, Scopus, EMBASE, EBSCO, Cochrane library, web of science, and google scholar was conducted from January 1975 to October 2018 limited to English language publications on administrations of photobiomodulation for bone regeneration which evaluated biological factors. In addition, hand search of selected journals was done to retrieve all articles. This systematic review was performed based on PRISMA guideline. Among these studies, five articles reported in vitro results, twelve articles were in vivo, and three of them were clinical trials. The data tabulated according to the type of markers (osteogenic markers, angiogenic markers, growth factors, and inflammation mediators). PBM's effects depend on many parameters which energy density is more important than the others. PBM can significantly enhance expression of osteocalcin, collagen, RUNX-2, vascular endothelial growth factor, bone morphogenic proteins, and COX-2. Although since the heterogeneity of the studies and their limitations, an evidence-based decision for definite therapeutic application of PBM is still unattainable, the findings of our review can help other researchers to ameliorate their study design and elect more efficient approach for their investigation.

Buccal fat pad-derived stem cells with anorganic bovine bone mineral scaffold for augmentation of atrophic posterior mandible: An exploratory prospective clinical study.

BACKGROUND: Application of adipose-derived stem cells originated from buccal fat pad (BFP) can simplify surgical procedures and diminish clinical risks compared to large autograft harvesting. PURPOSE: This study sought to evaluate and compare the efficacy of buccal fat pad-derived stem cells (BFPSCs) in combination with anorganic bovine bone mineral (ABBM) for vertical and horizontal augmentation of atrophic posterior mandibles. MATERIALS AND METHODS: Fourteen patients with atrophic posterior mandible were elected for this prospective exploratory study. BFP (3-5 mL) was harvested and BFPSCs were isolated and combined with ABBM at 50% ratio. The vertical and horizontal alveolar deficiencies were augmented by 50% mixture of ABBM with either BFPSCs (group 1) or particulated autologous bone (group 2). Titanium mesh was contoured to the desired 3D shape of the alveolar ridge and fixated to the host sites over the graft material of the two groups. At first, the amount of new bone areas was calculated by quantitative analysis of cone beam computed tomography (CBCT) images that were taken 6 months postoperatively according to regenerative techniques (group 1 vs group 2 without considering the type of bone defects). Second, these amounts were calculated in each group based on the type of defects. RESULTS: Quantitative analysis of CBCT images revealed the areas of new bone formation were 169.5 ± 5.90 mm2 and 166.75 ± 10.05 mm2 in groups 1 and 2, respectively. The area of new bone formation for vertical defects were 164.91 ± 3.74 mm2 and 169.36 ± 12.09 mm2 in groups 1 and 2, respectively. The area of new bone formation for horizontal deficiencies were 170.51 ± 4.54 mm2 and 166.98 ± 9.36 mm2 in groups 1 and 2, respectively. There were no statistically significant differences between the two groups in any of the pair-wise comparisons (P > 0.05). CONCLUSIONS: The findings of the present study demonstrated lack of difference in bone volume formation between BFPSCs and autologous particulate bone in combination with ABBM. If confirmed by future large-scale clinical trial, BFPSCs may provide an alternative to autogenous bone for reconstruction of alveolar ridge defects.