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.

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.

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.

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.

Association of vitamin D binding protein and vitamin D receptor gene polymorphisms in Iranian patients with chronic periodontitis.

Chronic periodontitis (CP) is a multifactorial disease and the most common type of periodontitis mainly caused by microbial plaque. Insufficient oral hygiene may initiate CP and it can be further modified and progressed by environmental and genetic susceptibilities. The aim of the present study was to investigate the association between VDBP (rs7041 and rs4588) and (Taq 1-rs7975232 and Apa1-rs731236) SNPs of VDR gene receptor and susceptibility to CP in an Iranian population. Sixty nine cases with diagnosis of CP and 78 matched healthy controls engaged in this study. Three-milliliter peripheral blood samples were obtained for DNA isolation. Genotype analysis was performed using restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). Chi-squared test was used for distribution of genotypes analysis. 95% confidence interval (CI) was used to calculate the odds ratio (OR). Deviation from Hardy-Weinberg equilibrium, multiple inheritance models, linkage disequilibrium and haplotype analysis were done. There was no significant association between genotype/phenotype of VDBP's SNPs (rs7041 and rs4588) and occurrence of chronic periodontitis (p value = 0.401) Moreover, no statistically significant association was found between chronic periodontitis and Taq1 (rs731236) (p value = 0.401) and Apa1 (rs7975232) (p value = 0.248). The analysis of alleles and genotypes' distribution between different severities of chronic periodontitis and healthy controls indicated a significant association between various severities of chronic periodontitis and Apa1 (rs7975232) (p value = 0.011) and VDBP's SNPs (rs7041 and rs4588) (p value = 0.038), whereas no statistically significant association was observed between various severities of chronic periodontitis and Taq1 (rs731236) (p value = 0.278). Our results suggest a significant association between severity of chronic periodontitis and Apa1 (rs7975232) and VDBP SNPs (rs7041 and rs4588). Sequencing studies on different populations may release other results due to the genetic and racial diversity.

Buccal Fat Pad-Derived Stem Cells in Three-Dimensional Rehabilitation of Large Alveolar Defects: A Report of Two Cases.

This case report seeks to describe efficient clinical application of adipose-derived stem cells (AdSCs) originated from buccal fat pad (BFP) in combination with conventional guided bone regeneration as protected healing space for reconstruction of large alveolar defects after extraction of multiple impacted teeth. The first case was a 19-year-old woman with several impacted teeth in the maxillary and mandibular regions, which could not be forced to erupt and were recommended for surgical extraction by the orthodontist. After this procedure, a large bone defect was created, and this space was filled by AdSC loaded natural bovine bone mineral (NBBM), which was protected with lateral ramus cortical plates, microscrews, and collagen membrane. After 6 months of post-guided bone regeneration, the patient received 6 and 7 implant placements, respectively, in the maxilla and mandible. At 10 months postoperatively, radiographic evaluation revealed thorough survival of implants. The second case was a 22-year-old man with the same complaint and large bony defects created after his teeth were extracted. After 6 months of post-guided bone regeneration, he received 4 dental implants in his maxilla and 7 implants in the mandible. At 48 months postoperatively, radiographs showed complete survival of implants. This approach represented a considerable amount of 3-dimensional bone formation in both cases, which enabled us to use dental implant therapy for rehabilitation of the whole dentition. The application of AdSCs isolated from BFP in combination with NBBM can be considered an efficient treatment for bone regeneration in large alveolar bone defects.

A modified frenectomy technique: a new surgical approach.

The frenum is a mucosal fold that attaches the lips or cheeks to the alveolar mucosa, gingiva, and underlying periosteum. Consequences of an abnormal frenal attachment include gingival recession, decreased vestibular depth, decreased range of lip movement, and involvement of interdental papilla, causing a diastema. Several methods to eliminate ectopic frenal attachments have been suggested, including frenectomy (elimination) and frenotomy (repositioning). This case report describes the use of a modified frenectomy technique in a 15-year-old girl with excess gingiva between the maxillary central incisors, which exhibited a 3-mm diastema. First, a semilunar primary incision was made in the palatal surface at a 5-mm distance from the tip of the papilla. Next, sulcular incisions were made around the tooth, and the papilla was transposed to the buccal via a papilla preservation flap. After complete elimination of frenal attachments in the bone, the flap was repositioned and sutured to the palatal surface. Afterward, the frenum was classically cut and sutured. Through this approach, the position of the frenum was changed apically without invading the papilla. At the 3-month follow-up, it was found that the modified technique (combination of papilla preservation flap and frenotomy) had minimized the surgical scar on the buccal surface, preserved the papilla, and yielded optimal esthetic results.

Timing of soft tissue management around dental implants: a suggested protocol.

Survival of dental implants depends on several factors; soft tissue (ST) management around dental implants is one of the foremost. Several studies have suggested techniques for ST management around dental implants, but none of them has discussed a suitable timetable for this process. This study aimed to review published articles related to the timing of ST management around dental implants and suggest a customized treatment protocol. A search of the PubMed database was conducted; the search was limited to English-language articles published from January 1995 to July 2015 with available full texts. Only in vivo studies and clinical trials in relation to the terms soft tissue management, management timing, keratinized mucosa, free gingival graft, connective tissue graft, soft tissue, augmentation, and dental implant were included. A total of 492 articles were reviewed, and eventually 42 articles were thoroughly evaluated. Those with treatment protocols in terms of the timing of ST grafting were selected and classified. ST management around dental implants may be done prior to the surgical phase, after the surgical phase, before loading, or even after loading. A thick gingival biotype is more suitable for implant placement, providing more favorable esthetic results. A treatment plan should be based on individual patient needs as well as the knowledge and experience of the clinician. The width and thickness of keratinized tissues, the need for bone management, and local risk factors that influence esthetic results determine the appropriate time for ST augmentation procedures.

Plasma Level Formaldehyde in Children Receiving Pulpotomy Treatment under General Anesthesia.

OBJECTIVES: Formocresol has long been used by dentists for pulpotomy of primary teeth. Due to some concerns regarding its possible carcinogenicity, formocresol has been the topic of numerous studies. This study sought to assess the changes in plasma level of formaldehyde of children after receiving pulpotomy under general anesthesia. STUDY DESIGN: Twenty-five children between 2-6 years requiring dental treatments under general anesthesia were studied. Blood samples were taken of children before and after the procedure. Plasma level of formaldehyde was measured using high performance liquid chromatography (HPLC). RESULTS: A total of 106 pulpotomy treatments were performed in 25 children using 126 cotton pellets dipped in formocresol. An increase and a decrease in plasma level of formaldehyde were noted in 5 (20%) and 20 (80%) children, respectively post-operatively compared to baseline. The t-test showed no significant difference in plasma level of formaldehyde pre- and postoperatively (P=0.12). the plasma level of formaldehyde in children who had higher levels of formaldehyde prior to the operation was also higher than that of others after the operation and this association was statistically significant (P=0.001, r=0.64). CONCLUSIONS: The results showed no significant change in the mean plasma level of formaldehyde in children who received pulpotomy under general anesthesia compared to its baseline value.

Feeding in Oral Cancer Patients After Massive Ablative Surgery: Percutaneous Endoscopic Gastrostomy or Nasogastric Tube.

Feeding after ablative oral cancer surgery is a major concern in postoperative care phase. The aim of this study was to compare postoperative phase of healing in patients undergoing nasogastric tube insertion and percutaneous endoscopic gastrostomy. In this single randomized clinical trial, 40 patients were randomly allocated to 2 groups according to a randomized list: group one (20 patients) had nasogastric tube for 4 weeks and group two (20 patients) underwent percutaneous endoscopic gastrostomy for 4 weeks or more after the surgery. Occurrence of infection and wound dehiscence was assessed. Weight loss was defined as reduction in patients' weight at 4 weeks after the surgery compared with preoperation. Weight loss was 7.9 ±â€Š1.91 kg in group one and 5.3 ±â€Š1.38 kg in group two; the difference in this regard between the 2 groups was statistically significant (P = 0.001). In group one, 10 subjects had dehiscence versus 3 subjects in group two; this difference was significant (P = 0.04). Analysis of the data demonstrated a significant difference in postsurgical infection between the 2 groups (P = 0.044). It seems that gastrostomy may be an appropriate method for feeding in patients with extensive oral cancer.

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.

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.

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.

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 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.

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.

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.

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.