Regenerative potential of platelet concentrates in chronic oral mucosal lesions.

Chronic oral mucosal diseases (COMDs) represent a significant challenge for clinicians and patients. They are commonly associated with chronic pain and negative effects on healing and patient's quality of life. Regenerative medicine including the use of biological autologous blood-derived substances (e.g., platelet concentrates [PCs]), has been reported to improve healing and reduce pain in orthopedic and maxillofacial surgeries as well as chronic oral mucosal diseases. In this review, we aim to describe the different types of PCs and their applications in the management of COMDs such as lichen planus, mucositis, pemphigus vulgaris, mucous membrane pemphigoid, and plasma cell mucositis, in terms of healing potential, pain control, and quality of life. Overall, PC applications seem to enhance healing and reduce pain in patients with COMDs. However, due to the small sample size and the lack of standardized clinical trials, further research is required to support these findings.

Integration of an evidence-based caries management approach in dental education: The perspectives of dental instructors.

PURPOSE/OBJECTIVES: Evidence-based caries management (EBCM) has developed into an internationally recognized tool for integration of comprehensive non-surgical caries treatment in dental education. However, uptake of the EBCM approach remains uneven across Canadian dental schools. Our project sought to understand how dental instructors perceive the challenges and solutions to the integration of the EBCM approach in undergraduate clinical education. METHODS: Using a qualitative descriptive design, we recruited a purposeful sample of clinical instructors supervising undergraduate dental students in caries-related dental care. Semi-structured, online interviews focused on the main characteristics of EBCM. Interviews were analyzed using the awareness, desire, knowledge, ability, and reinforcement (ADKAR) change management model to understand challenges with EBCM implementation in undergraduate education. The analysis process started with verbatim transcription; then, transcripts were coded deductively based on the interview guide and the ADKAR model domains, and inductively to generate emergent codes. Finally, thematic analysis was used to develop themes and subthemes. RESULTS: We interviewed 11 dental instructors with a wide range of clinical experience. Our results show that participants had sufficient awareness regarding the need for the EBCM approach and portrayed a strong desire to participate in bringing curricular changes. Knowledge and ability of participants depended on their training, experience, and involvement in continuing education courses. A lack of standardized caries management practices, less chairside time, and poor remuneration for instructors were major barriers in EBCM clinical implementation. Potential solutions suggested included providing continuing education courses, credits for students for non-surgical caries management, and remunerating instructors for implementation. CONCLUSIONS: In conclusion, most participants were aware of the need for a substantive change toward EBCM and demonstrated the desire to participate and improve its implementation. Our analysis showed that to facilitate full integration of the EBCM approach into the undergraduate dental clinics, organizational focus needs to be placed on the individual's knowledge and ability, with tailored efforts toward reinforcement.

Preclinical orofacial pain assays and measures and chronic primary orofacial pain research: where we are and where we need to go.

Chronic primary orofacial pain (OFP) conditions such as painful temporomandibular disorders (pTMDs; i.e., myofascial pain and arthralgia), idiopathic trigeminal neuralgia (TN), and burning mouth syndrome (BMS) are seemingly idiopathic, but evidence support complex and multifactorial etiology and pathophysiology. Important fragments of this complex array of factors have been identified over the years largely with the help of preclinical studies. However, findings have yet to translate into better pain care for chronic OFP patients. The need to develop preclinical assays that better simulate the etiology, pathophysiology, and clinical symptoms of OFP patients and to assess OFP measures consistent with their clinical symptoms is a challenge that needs to be overcome to support this translation process. In this review, we describe rodent assays and OFP pain measures that can be used in support of chronic primary OFP research, in specific pTMDs, TN, and BMS. We discuss their suitability and limitations considering the current knowledge of the etiology and pathophysiology of these conditions and suggest possible future directions. Our goal is to foster the development of innovative animal models with greater translatability and potential to lead to better care for patients living with chronic primary OFP.

EFFICACY OF 4% ARTICAINE BUCCAL INFILTRATION VERSUS INFERIOR ALVEOLAR NERVE BLOCK FOR MANDIBULAR MOLARS WITH SYMPTOMATIC IRREVERSIBLE PULPITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVES: To compare the anesthetic efficacy of buccal infiltration (BI) using 4% articaine vs 4% articaine or 2% lidocaine inferior alveolar nerve block (IANB) for mandibular molars with symptomatic irreversible pulpitis. METHODS: PubMed, Cochrane, Web of Science, Scopus, and ClinicalTrials.gov were searched using MESH terms and specific keywords. Included articles were Randomized Clinical Trials (RCTs), which compared 4% articaine BI vs conventional IANB in terms of the efficacy of pulpal anesthesia and success rate. The quality assessment of included studies was done according to the Cochrane risk of bias assessment tool. Studies were quantitatively assessed using fixed or random effect models. RESULTS: Out of 756 articles, 5 RCT studies were included with a total number of 500 patients: 231 in 4% articaine BI group, 150 in 2% lidocaine IANB group, and 119 in 4% articaine IANB group. Our meta-analysis results showed that patients anesthetized with 4% articaine BI had a similar success rate compared to 2% lidocaine IANB [pooled RD: 0.14 (95% CI, -0.01 to 0.29); P = .08]. Similarly, there was non-significant difference when compared to 4% articaine IANB [RD:-0.01 (95% CI, -0.13 to 0.11; P = .86)]. Patients anesthetized with 4% articaine BI presented comparable pain scores compared to IANB (4% articaine or 2% lidocaine) [pooled MD: -0.14 (95% CI, -0.38 to 0.11); P = .27]. Regarding quality assessment, 3 studies were considered to have a low risk of bias, one study has an unclear risk of bias, and one study has a high risk of bias. CONCLUSION: 4% articaine BI showed comparable results in terms of pain relief and success rate in comparison with 2% lidocaine IANB or 4% articaine IANB. However, due to the limited number and small sample size of included studies, these findings should be considered carefully, and further studies are required to confirm our findings.

Differences in platelet-rich plasma composition influence bone healing.

AIM: Platelet-rich plasma (PRP) is an autologous blood-derived material that has been used to enhance bone regeneration. Clinical studies, however, reported inconsistent outcomes. This study aimed to assess the effect of changes in leucocyte and PRP (L-PRP) composition on bone defect healing. MATERIALS AND METHODS: L-PRPs were prepared using different centrifugation methods and their regenerative potential was assessed in an in-vivo rat model. Bilateral critical-size tibial bone defects were created and filled with single-spin L-PRP, double-spin L-PRP, or filtered L-PRP. Empty defects and defects treated with collagen scaffolds served as controls. Rats were euthanized after 2 weeks, and their tibias were collected and analysed using micro-CT and histology. RESULTS: Double-spin L-PRP contained higher concentrations of platelets than single-spin L-PRP and filtered L-PRP. Filtration of single-spin L-PRP resulted in lower concentrations of minerals and metabolites. In vivo, double-spin L-PRP improved bone healing by significantly reducing the size of bone defects (1.08 ± 0.2 mm3 ) compared to single-spin L-PRP (1.42 ± 0.27 mm3 ) or filtered L-PRP (1.38 ± 0.28 mm3 ). There were fewer mast cells, lymphocytes, and macrophages in defects treated with double-spin L-PRP than in those treated with single-spin or filtered L-PRP. CONCLUSION: The preparation method of L-PRP affects their composition and potential to regenerate bone.

EFFICACY OF HEMOSTATIC AGENTS IN ENDODONTIC SURGERY: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS.

OBJECTIVE: Adequate hemostasis is a critical step in endodontic surgery. It facilitates the procedure and affects the success and prognosis of the operation. This systematic review and network meta-analysis (NMA) aimed to systematically assess the efficacy of hemostatic agents in endodontic surgery and to identify the most effective ones. METHODS: PubMed, Scopus, Embase, Cochrane Library, Web of Science, ProQuest, and EBSCOhost databases were searched up to December 2020. We included randomized controlled trials (RCTs) evaluating the efficacy of different hemostatic measures in endodontic surgery, and their risk of bias was assessed using Cochrane's randomized trial tool (RoB 2.0). Frequentist network meta-analysis was conducted, with Odds Ratios and 95% confidence intervals (OR, 95% CI) as effect estimates using the "netmeta" package in R. The quality of evidence was assessed using the CINeMA approach. RESULTS: Six RCTs involving 353 patients (mean age 48.12 y) were included. NMA revealed that aluminum chloride achieved higher hemostatic efficacy than epinephrine (OR = 2.55, 95% CI [1.41, 4.64]), while there was non-significant difference when compared with PTFE strips + epinephrine (OR = 1.00, 95% CI [0.35, 2.90]), electrocauterization (OR = 2.67, 95% CI [0.84, 8.46]), or ferric sulfate (OR = 8.65, 95% CI [0.31, 240.92]). Of all hemostatic agents, aluminum chloride ranked first in control bleeding during endodontic surgery (P-score = 0.84), followed by PTFE strips + epinephrine (P-score = 0.80), electrocauterization (P-score = 0.34), epinephrine (P-score = 0.34), ferric sulfate (P-score = 0.18). The quality of evidence was very low. CONCLUSIONS: Based on the limited data, aluminum chloride provides better hemostasis than epinephrine, while there was no significant difference between the remaining hemostatic agents used in endodontic surgery, which could help clinicians choose the hemostatic agent that achieves adequate hemostasis. achieve adequate hemostasis. Given insufficient evidence, future RCTs addressing this evidence gap are required.

Acetylcholinesterase inhibitors and risk of bleeding and acute ischemic events in non-hypertensive Alzheimer's patients.

INTRODUCTION: Acetylcholinesterase inhibitors (AChEIs) are commonly used to treat mild to moderate cases of Alzheimer disease (AD). To the best of our knowledge, there has been no study estimating the risk of bleeding and cardiovascular events in patients with non-hypertensive AD. Therefore, this study aimed to estimate the association between AChEIs and the risk of bleeding and cardiovascular ischemic events in patients with non-hypertensive AD. METHODS: A nested case-control study was conducted to estimate the risk of bleeding and ischemic events (angina, myocardial infarction [MI], and stroke) in patients with AD. This study was conducted using the UK Clinical Practice Research Datalink and Hospital Episode Statistics (HES) databases. The study cohort consisted of AD patients ≥65 years of age. The case groups included all AD subjects in the database who had a bleeding or ischemic event during the cohort follow-up. Four controls were selected for each case. Patients were classified as current users or past users based on a 60-day threshold of consuming the drug. Simple and multivariable conditional logistic regression analyses were used to calculate the adjusted odds ratio for bleeding events and cardiovascular events. RESULTS: We identified 507 cases and selected 2028 controls for the bleeding event cohort and 555 cases and 2220 controls for the ischemic event cohort. The adjusted odds ratio (OR) (95% confidence interval [CI]) for the association of AChEI use was 0.93 (0.75 to 1.16) for bleeding events, 2.58 (1.01 to 6.59) for angina, and 1.89 (1.07 to 3.33) for MI. Past users of AChEIs were also at increased risk of stroke (1.51 [1.00 to 2.27]). DISCUSSION: This is the first study assessing the risk of bleeding and cardiovascular events in patients with non-hypertensive AD. Our findings could be of great interest for clinicians and researchers working on AD.

High toughness resorbable brushite-gypsum fiber-reinforced cements.

The ideal bone substitute material should be mechanically strong, biocompatible with a resorption rate matching the rate of new bone formation. Brushite (dicalcium phosphate dihydrate) cement is a promising bone substitute material but with limited resorbability and mechanical properties. To improve the resorbability and mechanical performance of brushite cements, we incorporated gypsum (calcium sulfate dihydrate) and diazonium-treated polyglactin fibers which are well-known for their biocompatibility and bioresorbability. Here we show that by combining brushite and gypsum, we were able to fabricate biocompatible composite cements with high fracture toughness (0.47 MPa·m1/2) and a resorption rate that matched the rate of new bone formation. Adding functionalized polyglactin fibers to this composite cement further improved the fracture toughness up to 1.00 MPa·m1/2. XPS and SEM revealed that the improvement in fracture toughness is due to the strong interfacial bonding between the functionalized fibers and the cement matrix. This study shows that adding gypsum and functionalized polyglactin fibers to brushite cements results in composite biomaterials that combine high fracture toughness, resorbability, and biocompatibility, and have great potential for bone regeneration.

The effect of aging on the bone healing properties of blood plasma.

OBJECTIVES: Age-related changes in blood composition have been found to affect overall health. Thus, this study aimed to understand the effect of these changes on bone healing by assessing how plasma derived from young and old rats affect bone healing using a rat model. METHODS: . Blood plasma was collected from 6-month and 24-month old rats. Differences in elemental composition and metabolome were assessed using optical emission spectrometry and liquid mass spectrometry, respectively. Bilateral tibial bone defects were created in eight rats. Young plasma was randomly applied to one defect, while aged plasma was applied to the contralateral one. Rats were euthanized after two weeks, and their tibiae were analyzed using micro-CT and histology. The proteome of bone marrow was analyzed in an additional group of three rats. RESULTS: Bone-defects treated with aged-plasma were significantly bigger in size and presented lower bone volume/tissue volume compared to defects treated with young-plasma. Histomorphometric analysis showed fewer mast cells, macrophages, and lymphocytes in defects treated with old versus young plasma. The proteome analysis showed that young plasma upregulated pathways required for bone healing (e.g. RUNX2, platelet signaling, and crosslinking of collagen fibrils) whereas old plasma upregulated pathways, involved in disease and inflammation (e.g. IL-7, IL-15, IL-20, and GM-CSF signaling). Plasma derived from old rats presented higher concentrations of iron, phosphorous, and nucleotide metabolites as well as lower concentrations of platelets, citric acid cycle, and pentose phosphate pathway metabolites compared to plasma derived from young rats. CONCLUSION: bone defects treated with plasma-derived from young rats showed better healing compared to defects treated with plasma-derived from old rats. The application of young and old plasmas has different effects on the proteome of bone defects.

Correction: Antegrade versus retrograde facial nerve dissection in benign parotid surgery: Is there a difference in postoperative outcomes? A meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0206028.].

A Novel Technique to Increase the Thickness of TiO2 of Dental Implants by Nd: DPSS Q-sw Laser Treatment.

High bone-implant contact is a crucial factor in the achievement of osseointegration and long time clinical success of dental implants. Micro, nano, microtopography, and oxide layer of dental implants influence tissue response. The lasers were used for achieving an implant surface with homogeneous micro texturing and uncontaminated surface. The present study aimed to characterize the implant surfaces treated by Nd: DPSS Q-sw Laser treatment compared to machined implants. A total of 10 machined implants and 10 lasered surface implants were evaluated in this study. The implant surfaces were evaluated by X-ray Photoelectron Spectroscopy (XPS), Auger Electron Spectroscopy (AES), and metallography to characterize and measure the thickness of the oxide layer on the implant titanium surface. The machined surfaces showed a non-homogeneous oxide layer ranging between 20 and 30 nm. The lasered implant surfaces showed a homogeneous oxide layer ranging between 400 nm and 460 nm in the area of the laser holes, while outside the layer, thickness ranged between 200 nm and 400 nm without microcracks or evidence of damage. Another exciting result after this laser treatment is a topographically controlled, repeatable, homogeneous, and clean surface. This technique can obtain the implant surface without leaving residues of foreign substances on it. The study results indicate that the use of Nd: DPSS Q-sw laser produces a predictable and reproducible treatment able to improve the titanium oxide layer on the dental implant surface.

Postoperative Administration of the Acetylcholinesterase Inhibitor, Donepezil, Interferes with Bone Healing and Implant Osseointegration in a Rat Model.

Donepezil is an acetylcholinesterase inhibitor commonly used to treat mild to moderate Alzheimer's disease. Its use has been associated with increased bone mass in humans and animals. However, the effect of postoperative administration of donepezil on bone healing remains unknown. Therefore, this study aimed to assess the impact of postoperative injection of donepezil on bone healing, titanium-implant osseointegration, and soft tissue healing. Twenty-two Sprague-Dawley rats were randomly assigned to receive a daily dose of either donepezil (0.6 mg/kg) or saline as a control. In each rat, a uni-cortical defect was created in the right tibia metaphysis and a custom-made titanium implant was placed in the left tibiae. After two weeks, rats were euthanized, and their bones were analysed by Micro-CT and histology. The healing of bone defect and implant osseointegration in the rats treated with donepezil were significantly reduced compared to the saline-treated rats. Histomorphometric analysis showed lower immune cell infiltration in bone defects treated with donepezil compared to the saline-treated defects. On the other hand, the healing time of soft tissue wounds was significantly shorter in donepezil-treated rats compared to the controls. In conclusion, short-term administration of donepezil hinders bone healing whereas enhancing soft tissue healing.

Ranitidine Impairs Bone Healing and Implant Osseointegration in Rats' Tibiae.

PURPOSE: Ranitidine has been found to have an impact on bone metabolism by suppressing osteoclastogenesis. We hypothesized that the use of ranitidine would impair bone healing and implant osseointegration. This study investigated the effect of postoperative administration of ranitidine on bone healing and osseointegration in rats. MATERIALS AND METHODS: Twenty-two Sprague-Dawley rats underwent surgery to create a unicortical bone defect in each tibia. A titanium implant was placed on the right tibial defect, whereas the contralateral defect was left unfilled. After surgery, the rats were randomly divided into 2 groups receiving a daily dose of ranitidine or saline solution for 14 days and then euthanized for assessment of bone healing and osseointegration using micro-computed tomography (CT) and histomorphometry. RESULTS: Micro-CT analysis of the bone defect showed a larger bone defect volume in the ranitidine group (0.82 ± 0.13 µL vs 0.66 ± 0.16 µL, P = .034), thinner cortical thickness (0.54 ± 0.07 mm vs 0.63 ± 0.11 mm, P = .026), and less bone regeneration at the defect site (40% ± 12% vs 57% ± 11%, P = .003). Implant-site micro-CT analysis showed less osseointegration in the ranitidine group (34.1% ± 2.7% vs 43.5% ± 2.1%, P = .014), and implant-site histologic analysis showed less medullary (P = .021), cortical (P = .001), and total (P = .003) bone-implant contact and less peri-implant bone volume-tissue volume (P = .002) in the ranitidine group. Histologic analysis for osteoclastic activity showed a lower number of osteoclasts in the ranitidine group (4.8 ± 2.4 mm-2 vs 9.1 ± 2.1 mm-2, P = .026). CONCLUSIONS: The postoperative use of ranitidine impaired bone healing and osseointegration.

Regenerative Effect of Platelet Concentrates in Oral and Craniofacial Regeneration.

Platelet concentrates (PCs) are biological autologous products derived from the patient's whole blood and consist mainly of supraphysiologic concentration of platelets and growth factors (GFs). These GFs have anti-inflammatory and healing enhancing properties. Overall, PCs seem to enhance bone and soft tissue healing in alveolar ridge augmentation, periodontal surgery, socket preservation, implant surgery, endodontic regeneration, sinus augmentation, bisphosphonate related osteonecrosis of the jaw (BRONJ), osteoradionecrosis, closure of oroantral communication (OAC), and oral ulcers. On the other hand, no effect was reported for gingival recession and guided tissue regeneration (GTR) procedures. Also, PCs could reduce pain and inflammatory complications in temporomandibular disorders (TMDs), oral ulcers, and extraction sockets. However, these effects have been clinically inconsistent across the literature. Differences in study designs and types of PCs used with variable concentration of platelets, GFs, and leucocytes, as well as different application forms and techniques could explain these contradictory results. This study aims to review the clinical applications of PCs in oral and craniofacial tissue regeneration and the role of their molecular components in tissue healing.

Antegrade versus retrograde facial nerve dissection in benign parotid surgery: Is there a difference in postoperative outcomes? A meta-analysis.

OBJECTIVE: The primary aim of this meta-analysis was to test the null hypothesis of no difference in facial nerve dysfunction in studies that compared classical antegrade facial nerve dissection (AFND) versus retrograde facial nerve dissection (RFND) during benign parotid surgery. METHODS: A comprehensive search of PubMed, the Cochrane Central Register of Controlled Trials, Scopus, Google Scholar, Science Direct and relevant journals was undertaken up to June 27, 2018. Randomized controlled clinical trials (RCTs), controlled clinical trials (CCTs), and retrospective studies aimed at comparing the effect of AFND vs. RFND during parotidectomy were included. The outcome measures included facial nerve dysfunction, Frey's syndrome, recurrence, silaocele, salivary fistula, operating time length of hospital stay, and estimated blood loss. Pooled risk ratio (RR) and weighted mean differences (MD) with 95% confidence intervals were calculated using either a fixed-effects or random-effects model. RESULTS: Ten studies; four RCTs and five retrospective studies were included. There were 570 patients (319 in RFND group and 251 in AFND group). 481 patients in 9 studies reported the incidence rate of facial nerve dysfunction. No statistical significant difference was observed between both groups concerning the occurrence of transient or permanent facial nerve paralysis (p = 0.44 and 0.11 respectively). One out 10 studies reported the incidence rate of sialocele, however no statistical difference was observed between the two techniques. There was reduction in the operative time (19.30 min), amount of blood loss (25.08 ml) and amount of healthy salivary tissues removed (12.20 mm) in RFND compared with AFND. CONCLUSIONS: According to the results of the current review there is no evidence demonstrating a significant advantage of one approach over another, therefore, well-designed standardized RCTs are required.

Efficacy of Platelet-Rich Fibrin After Mandibular Third Molar Extraction: A Systematic Review and Meta-Analysis.

PURPOSE: To assess the effect of platelet-rich fibrin (PRF) on the healing process of the alveolar socket after surgical extraction of the mandibular third molars. MATERIALS AND METHODS: PubMed, the Cochrane Central Register of Controlled Trials, Scopus, and relevant journals were searched using a combination of specific keywords ("platelet-rich fibrin," "oral surgery," and "third molar"). The final search was conducted on November 2, 2015. Randomized controlled clinical trials, as well as controlled clinical trials, aimed at comparing the effect of PRF versus natural healing after extraction of mandibular third molars were included. RESULTS: Five randomized controlled trials and one controlled clinical trial were included. There were 335 extractions (168 with PRF and 167 controls) in 183 participants. Considerable heterogeneity in study characteristics, outcome variables, and estimated scales was observed. Positive results were generally recorded for pain, trismus, swelling, periodontal pocket depth, soft tissue healing, and incidence of localized osteitis, but not in all studies. However, no meta-analysis could be conducted for such variables because of the different measurement scales used. The qualitative and meta-analysis results showed no significant improvement in bone healing with PRF-treated sockets compared with the naturally healing sockets. CONCLUSIONS: Within the limitations of the available evidence, PRF seems to have no beneficial role in bone healing after extraction of the mandibular third molars. Future standardized randomized controlled clinical trials are required to estimate the effect of PRF on socket regeneration.