Understanding exosomes: Part 2-Emerging leaders in regenerative medicine.

Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due to their ability to be utilized as therapeutic options for a wide array of diseases/conditions. Over 5000 publications are currently being published yearly on this topic, and this number is only expected to dramatically increase as novel therapeutic strategies continue to be developed. Today exosomes have been applied in numerous contexts including neurodegenerative disorders (Alzheimer's disease, central nervous system, depression, multiple sclerosis, Parkinson's disease, post-traumatic stress disorders, traumatic brain injury, peripheral nerve injury), damaged organs (heart, kidney, liver, stroke, myocardial infarctions, myocardial infarctions, ovaries), degenerative processes (atherosclerosis, diabetes, hematology disorders, musculoskeletal degeneration, osteoradionecrosis, respiratory disease), infectious diseases (COVID-19, hepatitis), regenerative procedures (antiaging, bone regeneration, cartilage/joint regeneration, osteoarthritis, cutaneous wounds, dental regeneration, dermatology/skin regeneration, erectile dysfunction, hair regrowth, intervertebral disc repair, spinal cord injury, vascular regeneration), and cancer therapy (breast, colorectal, gastric cancer and osteosarcomas), immune function (allergy, autoimmune disorders, immune regulation, inflammatory diseases, lupus, rheumatoid arthritis). This scoping review is a first of its kind aimed at summarizing the extensive regenerative potential of exosomes over a broad range of diseases and disorders.

Understanding exosomes: Part 3-therapeutic + diagnostic potential in dentistry.

Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due to their ability to be utilized as therapeutic options for a wide array of various diseases. Over 5000 publications are currently being published on this topic yearly, many of which in the dental space. This extensive review article is the first scoping review aimed at summarizing all therapeutic uses of exosomes in regenerative dentistry. A total of 944 articles were identified as using exosomes in the dental field for either their regenerative/therapeutic potential or for diagnostic purposes derived from the oral cavity. In total, 113 research articles were selected for their regenerative potential (102 in vitro, 60 in vivo, 50 studies included both). Therapeutic exosomes were most commonly derived from dental pulps, periodontal ligament cells, gingival fibroblasts, stem cells from exfoliated deciduous teeth, and the apical papilla which have all been shown to facilitate the regenerative potential of a number of tissues including bone, cementum, the periodontal ligament, nerves, aid in orthodontic tooth movement, and relieve temporomandibular joint disorders, among others. Results demonstrate that the use of exosomes led to positive outcomes in 100% of studies. In the bone field, exosomes were found to perform equally as well or better than rhBMP2 while significantly reducing inflammation. Periodontitis animal models were treated with simple gingival injections of exosomes and benefits were even observed when the exosomes were administered intravenously. Exosomes are much more stable than growth factors and were shown to be far more resistant against degradation by periodontal pathogens found routinely in a periodontitis environment. Comparative studies in the field of periodontal regeneration found better outcomes for exosomes even when compared to their native parent stem cells. In total 47 diagnostic studies revealed a role for salivary/crevicular fluid exosomes for the diagnosis of birth defects, cardiovascular disease, diabetes, gingival recession detection, gingivitis, irritable bowel syndrome, neurodegenerative disease, oral lichen planus, oral squamous cell carcinoma, oropharyngeal cancer detection, orthodontic root resorption, pancreatic cancer, periodontitis, peri-implantitis, Sjögren syndrome, and various systemic diseases. Hence, we characterize the exosomes as possessing "remarkable" potential, serving as a valuable tool for clinicians with significant advantages.

Extended platelet-rich fibrin.

Platelet-rich fibrin (PRF) has been characterized as a regenerative biomaterial that is fully resorbed within a typical 2-3 week period. Very recently, however, a novel heating process was shown to extend the working properties of PRP/PRF from a standard 2-3 week period toward a duration of 4-6 months. Numerous clinicians have now utilized this extended-PRF (e-PRF) membrane as a substitute for collagen barrier membranes in various clinical applications, such as guided tissue/bone regeneration. This review article summarizes the scientific work to date on this novel technology, including its current and future applications in periodontology, implant dentistry, orthopedics and facial aesthetics. A systematic review was conducted investigating key terms including "Bio-Heat," "albumin gel," "albumin-PRF," "Alb-PRF," "extended-PRF," "e-PRF," "activated plasma albumin gel," and "APAG" by searching databases such as MEDLINE, EMBASE and PubMed. Findings from preclinical studies demonstrate that following a simple 10-min heating process, the transformation of the liquid plasma albumin layer into a gel-like injectable albumin gel extends the resorption properties to at least 4 months according to ISO standard 10 993 (subcutaneous animal model). Several clinical studies have now demonstrated the use of e-PRF membranes as a replacement for collagen membranes in GTR/GBR procedures, closing lateral windows in sinus grafting procedures, for extraction site management, and as a stable biological membrane during recession coverage procedures. Furthermore, Alb-PRF may also be injected as a regenerative biological filler that lasts extended periods with advantages in joint injections, osteoarthritis and in the field of facial aesthetics. This article highlights the marked improvement in the stability and degradation properties of the novel Alb-PRF/e-PRF technology with its widespread future potential use as a potential replacement for collagen membranes with indications including extraction site management, GBR procedures, lateral sinus window closure, recession coverage among others, and further highlights its use as a biological regenerative filler for joint injections and facial aesthetics. It is hoped that this review will pioneer future opportunities and research development in the field, leading to further progression toward more natural and less costly biomaterials for use in medicine and dentistry.

Dental Diode Lasers for Implant Uncovering: A Case Series.

Diode lasers are increasingly being utilized as an alternative to conventional soft tissue surgery. Diode lasers originally referred to wavelengths ranging from 810 to 980 nm, but a visible diode laser with a 445-nm wavelength has emerged as an additional wavelength for soft tissue surgery. The goal of this case series was to demonstrate the clinical results of both visible and near-infrared (NIR) wavelengths when utilized for stage-two implant surgery. Ten patients with 23 implants were treated at Stony Brook University, Department of Periodontology, for implant uncovering using both visible and nonvisible (NIR) diode lasers. The uncovering was performed utilizing 445-, 970-, and 980-nm wavelengths at a power setting of 2 W in either continuous or pulsed modes. The fiberoptic tips were initiated using blue articulating paper. Either topical benzocaine or infiltration anesthesia was utilized prior to soft tissue removal with the initiated tip. All patients healed uneventfully without any postoperative complications. Visible and NIR diode lasers provide an alternative and safe method to uncover submerged implants at stage-two surgery.

Biological Characterization, Properties, and Clinical Use of a Novel Homeopathic Antiseptic Oral Recovery Kit: A Narrative Review.

Most available antiseptic solutions have strong antibacterial effects, but many also possess major cytotoxic effects on gingival fibroblasts, osteoblasts, osteoprogenitor cells, and/or epithelial cells. A novel VEGA Oral Care Recovery Kit (StellaLife) consisting of 16 active ingredients that are monographed in the Homeopathic Pharmacopeia of the United States (HPUS) has gained tremendous momentum as a replacement for more cytotoxic oral rinses such as chlorhexidine. While accumulating evidence has thus far supported its use, little of the gathered data have fully described the properties of the oral formulation. Therefore, the aim of the present review article was 3-fold. First, a biological characterization regarding the active ingredients found in StellaLife Recovery Kit including their biological properties was assessed in 4 predominant categories; 1) antimicrobial resistance, 2) accelerated wound healing, 3) pain management control, and 4) anti-cancer properties. The second aim of this review article was to assess both fundamental and clinical research to date comparing VEGA oral rinse (StellaLife) to the more commonly utilized CHX for differences regarding their effect on decreasing bacterial loads as well as cell viability, survival, proliferation, and expression of both regenerative cytokines and inflammatory markers. Lastly, clinical case examples are presented describing the use of StellaLife remedies in a variety of clinical situations. These include but are not limited to wisdom-tooth extraction, extraction site management, dental implants and ridge augmentation, soft-tissue grafting procedures, frenectomies, and also temporary relief of dry sockets, dry mouth, aphthous ulcers, mucositis, lichen planus, among others. In summary, findings from the present review article provide evidence from basic laboratory experiments that validate clinical studies supporting the use of the StellaLife oral rinse regarding its superior biocompatibility and wound healing properties when compared to common antiseptic solutions such as CHX.

Use of Enamel Matrix Derivative in Minimally Invasive/Flapless Approaches: A Systematic Review with Meta-Analysis.

PURPOSE: The aim of the present systematic review with meta-analysis was to investigate the clinical effectiveness of EMD (enamel matrix derivative) using a minimally invasive surgical technique (MIST) or flapless approach for the treatment of severe periodontal probing depths. MATERIALS AND METHODS: A systematic review of the literature including searches in PubMed/Medline, Cochrane Library, Google Scholar, and Grey Literature databases as well as manual searches was performed on September 1st, 2021. Studies utilising EMD in a non-surgical or minimally invasive approach were included. The eligibility criteria comprised randomised controlled trials (RCTs) comparing minimally-invasive/flapless approaches with/without EMD for the treatment of probing depths >5 mm. RESULTS: From 1525 initial articles, 7 RCTs were included and 12 case series discussed. Three studies investigated a MIST approach, whereas 3 studies utilised a flapless approach. One study compared EMD with either a MIST or a flapless approach. The RCTs included ranged from 19-49 patients with at least 6 months of follow-up. While 5 of the studies included smokers, patients smoking >20 cigarettes/day were excluded from the study. The meta-analysis revealed that EMD with MIST improved recession coverage (REC) and bone fill (BF) when compared to MIST without EMD. However, no difference in CAL or PD was observed between MIST + EMD vs MIST without EMD. No statistically significant advantage was found for employing the EMD via the flapless approach. CONCLUSIONS: Implementing EMD in MIST procedures displayed statistically significant improvement in REC and BF when compared to MIST alone. These findings suggest that MIST in combination with EMD led to improved clinical outcomes while EMD employed in nonsurgical flapless therapy yielded no clinical benefits when compared to nonsurgical therapy alone without EMD. More research is needed to substantiate these findings.

Thermal Penetration Depth of Pulsed Lasers in Gingival Tissues: An In Vitro Study.

Background: With laser irradiation emerging as an adjunctive treatment utilized in nonsurgical periodontal therapy, it is important to understand the variance of penetration depth among the different laser wavelengths. Purpose: To evaluate the thermal penetration depth, as a photothermal effect, of carbon dioxide (CO2)-, erbium: doped yttrium-aluminum-garnett (Er:YAG)-, and erbium, chromium: yttrium-scandium-gallium-garnett (Er,Cr:YSGG)-lasers on the bovine gingiva in an in vitro model. Methods: Four mandibles from freshly slaughtered cows were utilized in this study. Buccal and lingual root debridement was provided using three different laser wavelengths, all in pulsed settings. A CO2- (10,600 nm), Er:YAG- (2940 nm), and Er,Cr:YSGG- (2780 nm) were utilized to irradiate pockets of two mandibular posterior teeth in each group. Laser power output settings were set to 2 W. The posterior teeth were irradiated for 30 sec buccal and 30 sec lingual of each tooth for all selected treatment test groups. Instrumentation with curettes was performed as a control group. Gingival flaps, including the entire gingiva, were fixed in 10% formalin and stained via Elastin van Gieson. Sections were examined microscopically to evaluate thermal damage and statistically compared using mixed effect model with Tukey adjustment. Results: The CO2-laser irradiation presented a statistically significant lower mean compared to Er,Cr:YSGG-laser (p < 0.0001). Er,Cr:YSGG-laser had a higher penetration depth compared to Er:YAG-laser (p < 0.0001). There was no statistically significant difference found in penetration depth between CO2- and Er:YAG-laser irradiation. Conclusions: It can be concluded that all tested pulsed lasers had minimal penetration depth into the gingiva. However, the pulsed CO2- and Er:YAG-lasers presented lower thermal effects compared to Er,Cr:YSGG-laser in vitro.

Combination of Nd:YAG and Er:YAG lasers in non-surgical periodontal therapy: a systematic review of randomized clinical studies.

Lasers are increasingly utilized in the non-surgical treatment of periodontal disease. The aim of the present systematic review with meta-analysis was to investigate the combination use of Nd:YAG and Er:YAG laser therapy in the treatment of severe periodontitis. A systematic review of the literature including searches in PubMed/Medline, Cochrane Library, Google Scholar, and Grey Literature databases, as well as manual searches, was performed until November 1, 2021. Only studies a combination of lasers during non-surgical treatment of pockets ≥ 6mm were included. The eligibility criteria for meta-analysis comprised randomized controlled trials (RCTs) comparing the use of combination laser therapy with/without adjunctive mechanical for the non-surgical management of periodontitis. From 57 initial articles, 6 full-text articles were assessed for eligibility. Two studies were excluded, one study was not a randomized clinical trial (case series), and one study was an in vitro study. Four RCTs were included in the meta-analysis. It was shown that combination of Nd:YAG and Er:YAG may be beneficial for non-surgical periodontal therapy with an additional average reduction in pocket depth and clinical attachment level reported at 1.01 and 0.77 mm respectively when compared to controls. The findings suggest that the combination of Nd:YAG and Er:YAG lasers may lead to additional clinical improvements compared to nonsurgical treatment alone. Future research is needed to substantiate these findings and optimize clinical guidelines including more specific laser protocols. Preliminary data suggest favorable outcomes following the combination of Nd:YAG and Er:YAG lasers for non-surgical periodontal therapy.

Evaluation of length and location of the maxillary sinus intraosseous artery using computerized tomography.

BACKGROUND: The intraosseous artery is a branch of the posterior superior alveolar artery that supplies the lateral wall of the maxillary sinus. The present study seeks to analyze the location of the intraosseous artery and its site of termination. METHODS: Cone beam computed tomography was used to evaluate 200 patients making up 400 maxillary sinuses. The following criteria were measured: (1) the distance of the lower border of the intraosseous artery to the floor of the sinus, (2) the average length of the artery, (3) the diameter of the artery, (4) the site at which the artery terminates at, and (5) the distance of the artery from the first premolar, second premolar, first molar, second molar, and third molar. RESULTS: The intraosseous artery was identified in 336 (84.0%) quadrants. The most common site of termination was at the mesial of the second molar (22%), regardless of dental status and right or left quadrant. Its overall mean diameter was 0.91 ± 0.56 mm, with no difference within the dental status. Its overall mean length was 7.40 ± 3.39 mm, with a statistically significant difference between dentate and edentulous quadrants (P < 0.001). Its overall mean distance from the floor was 6.95 ± 6.49 mm, with no difference within the dental status. All parameters showed no difference between right or left quadrants. CONCLUSIONS: The chances of encountering the intraosseous artery at the premolar area is <21% during a lateral window sinus floor elevation. The most common (22%) site of termination of the intraosseous artery is at the mesial of the second molar. Understanding of the course, location, and termination of the artery enhances the precision of a clinician when it comes to pre-operative treatment planning.

Prevalence and anatomical characteristics of the accessory mental foramen: a study using cone beam computed tomography.

The purpose of this study was to evaluate the prevalence of accessory mental foramina (AMFs) through the use of cone beam computed tomography (CBCT). The secondary purpose was to analyze the location of AMFs, mean distance from the nearest tooth, mean distance from the alveolar bone crest, exit angle dimensions, and whether sex, side of the mandible, or racial disparities exist. Two hundred CBCT scans were analyzed for the presence and characteristics of bifurcations of the inferior alveolar nerve. AMFs were observed in 11.5% of patients and 6.5% of all hemimandibles examined. The majority of patients with 1 or more AMFs were female (60.9%). Bilateral AMFs were found in 1.52% of patients. The location of the AMF relative to the mental foramen (MF) was evaluated, and 30.0% of AMFs were located anterosuperiorly and 23.3% posterosuperiorly to the MF. Associations between patient sex and the greatest and smallest diameters of AMFs, circumference and area of AMFs, and ratio of AMF-MF area were evaluated via statistical analysis. Additional analyses evaluated the prevalence on each side of the mandible as well as the association between race/ethnicity and occurrence of AMFs. Statistical analyses showed no association between the occurrence of AMFs and sex, side of the mandible, or race/ethnicity of the study population. This demonstrates the importance of preoperative CBCT prior to all mandibular surgery to reduce the risk of injury to the neurovascular bundles that pass through AMFs.

Utilization of cone beam computed tomography to determine the prevalence and anatomical characteristics of bifurcated inferior alveolar nerves.

The primary purpose of this study was to evaluate the prevalence of inferior alveolar nerve (IAN) bifurcations through the utilization of cone beam computed tomography (CBCT). The secondary purposes of this study were to analyze the average distance from the main trunk to its branch at the greatest point, to calculate the average distance of the bifid IAN from the apices of the teeth, and to determine the appropriate classification for each IAN bifid nerve according to the types described by Nortjé et al: type 1, 2 canals originating from a single foramen with a narrower inferior canal; type 2, 2 canals originating from a single foramen with a superior canal extending to the second or third molar; type 3, 2 canals of equal size that arise from 2 mental foramina that may link into a single canal near the molars. Examination of 194 CBCT scans revealed that IAN bifurcations were present in 13.4% (n = 26) of the study population. Bifurcation was bilateral in 4 individuals. For left bifurcated IANs, the average distance between the superior border of the main branch and inferior border of the bifurcated IAN (GDN) was 3.41 mm. The average distance from the superior border of the bifurcated IAN to the apex of the closest root (NAP) was 3.45 mm. For right bifurcated IANs, the average GDN was 4.01 mm, and the average NAP was 4.85 mm. Fourteen bifid nerves were type 1, and 16 were type 2. Preoperative CBCT studies can determine the presence of a bifurcated IAN, thereby reducing the chances of neurologic damage.