Investigation of the early apical release from endodontic hydrogels: A 3D printed model.

AIM: Regenerative Endodontic Procedures (REPs) using new materials such as hydrogels aim to replace current endodontic treatments, but numerous limitations are to overcome. Apical release was little explored in previous studies, especially regarding hydrogels that incorporate molecules, such as growth factors and antibiotics. Apical release is a key mechanism in achieving regeneration, as it could regulate disinfection or cell colonization. Few models exist for apical release, limiting the transfer of these devices from bench to bedside. This study aims to design a simple and standardized model to identify parameters that influence the early apical release kinetic of molecules from endodontic hydrogels. METHODOLOGY: Endodontic Release Inserts (ERI) were designed to mimic the situation of an immature incisor using three different diameters (Ø 0.5 to 2 mm) and to allow the study of the early release from a hydrogel in a 96-well plate. ERI was produced with a 3D printing machine. The kinetic release was investigated using 2 fluorescent, hydrophobic (BDP-500) and hydrophilic (Fluorescein) molecules, in different hydrogels (fibrin and agarose) and in various media (PBS or serum). The release kinetics were estimated by measuring the fluorescence at different time points (1 to 24 h). RESULTS: ERI use made it possible to report that apical diameters increase from 500 to 1000 µm was associated with an increase in release from 4.02 ± 1.63% to 11.53 ± 2.38% over 24 h. It also allowed us to report that bottom solution composition change from PBS to human serum was associated with an increase in the release of fatty acid molecules, whilst a decrease in the hydrogel concentration was associated with a variation in release kinetics. Moreover, nano-encapsulation of a molecule was associated with a decreased release over the first 24 h from 5.25 to 0%. CONCLUSION: ERI use enables investigation of the parameters influencing release kinetics from endodontic hydrogels. Further investigations are necessary to evaluate the interaction of these parameters with each other, in animal models and clinic.

Bioactive Endodontic Hydrogels: From Parameters to Personalized Medicine.

Regenerative endodontic procedures (REPs) aim at recreating dental pulp tissue using biomaterials such as hydrogels. Their bioactivity is mostly related to the nature of biomolecules or chemical compounds that compose the endodontic hydrogel. However, many other parameters, such as hydrogel concentration, bioactive molecules solubility, and apex size, were reported to influence the reciprocal host-biomaterial relationship and hydrogel behavior. The lack of knowledge regarding these various parameters, which should be considered, leads to the inability to predict the clinical outcome and suggests that the biological activity of endodontic hydrogel is impossible to anticipate and could hinder the bench-to-bedside transition. We describe, in this review, that most of these parameters could be identified, described, and studied. A second part of the review lists some challenges and perspectives, including development of future mathematical models that are able to explain, and eventually predict, the bioactivity of endodontic hydrogel used in a clinical setting.

Next generation antibacterial strategies for regenerative endodontic procedures: A scoping review.

BACKGROUND: The clinical results following regenerative endodontic procedures (REPs) vary according to numerous parameters, including the presence of bacteria. This limitation reduces the indications for REPs and calls for the development of next generation antibacterial strategies (NGAS) providing alternatives to current antibacterial strategies (CAS) such as double or triple antibiotic paste (DAP/TAP) and (Ca(OH)2). OBJECTIVES: The present scoping review aims to describe the current trends regarding the use of such strategies and highlight future perspectives. METHODS: Four databases (PUBMed, Cochrane, ClinicalTrials and Science Direct) were searched until 1st May 2023. RESULTS: A total of 918 records were identified, 133 were screened and assessed for eligibility, and 87 articles were included. The findings show that (1) clinical studies are only available for CAS, (2) although next generation strategies are the most studied approach since 2017, they are all at the pre-clinical stage, (3) most of the next generation strategies use galenic forms which offer cell support and colonization and which simultaneously contain antibacterial molecules as alternatives to CAS and to antibiotics in general, (4) standardization is required for future research, specifically regarding the bacterial strains studied, the use of biofilm studies and the cellular behaviour assessments. CONCLUSION: Although NGAS are promising strategies to improve REPs in the context of infection, the current evidence is mostly limited to pre-clinical studies. Further methodological improvement is required to allow relevant comparisons between studies and to reduce the time from bench to bedside.

Surgical treatment by electrical stimulation of the auditory cortex for intractable tinnitus.

Tinnitus is a public health issue in France. Around 1% of the population is affected and 30,000 people are handicapped in their daily life. The treatments available for disabling tinnitus have until now been disappointing. We are reporting on the surgical treatment by electrical stimulation of the auditory cortex of a female patient affected by disabling tinnitus that resisted classical treatments. The tinnitus appeared suddenly 10 years ago after a left ear tympanoplasty. The acouphenometry measures revealed a bilateral tinnitus, predominant on the right side, constant, with high frequency (6000 Hz). Transcranial magnetic stimulation (TMS) was performed at first with several supraliminal and infraliminal protocols. This showed promising results. Anatomic and functional magnetic resonance imaging (fMRI) of the auditory cortex before and after repetitive TMS (rTMS) demonstrated a modification of the cortical activity and where the ideal location for a cortical electrode might be, to straddle primary and secondary auditory cortex. After these investigations, two quadra polar electrodes (Resume, Medtronic Ltd, Hertfordshire, UK), connected to a stimulating device implanted under the skin (Synergy, Medtronic Ltd), were extradurally implanted. The surgical procedure was similar to the one performed for analgesic cortical stimulation. No surgical complications were reported. The activation of the stimulator provided a reduction of 65% of the tinnitus impact, with a persistent effect on the right side. The feasibility of the cortical stimulation in symptomatic treatment of tinnitus was proven by this preparatory work. The middle- and long-term therapeutic effects remain to be evaluated.

Whole mitochondrial genome screening in maternally inherited non-syndromic hearing impairment using a microarray resequencing mitochondrial DNA chip.

Mitochondrial DNA (mtDNA) mutations have been implicated in non-syndromic hearing loss either as primary or as predisposing factors. As only a part of the mitochondrial genome is usually explored in deafness, its prevalence is probably under-estimated. Among 1350 families with non-syndromic sensorineural hearing loss collected through a French collaborative network, we selected 29 large families with a clear maternal lineage and screened them for known mtDNA mutations in 12S rRNA, tRNASer(UCN) and tRNALeu(UUR) genes. When no mutation could be identified, a whole mitochondrial genome screening was performed, using a microarray resequencing chip: the MitoChip version 2.0 developed by Affymetrix Inc. Known mtDNA mutations was found in nine of the 29 families, which are described in the article: five with A1555G, two with the T7511C, one with 7472insC and one with A3243G mutation. In the remaining 20 families, the resequencing Mitochip detected 258 mitochondrial homoplasmic variants and 107 potentially heteroplasmic variants. Controls were made by direct sequencing on selected fragments and showed a high sensibility of the MitoChip but a low specificity, especially for heteroplasmic variations. An original analysis on the basis of species conservation, frequency and phylogenetic investigation was performed to select the more probably pathogenic variants. The entire genome analysis allowed us to identify five additional families with a putatively pathogenic mitochondrial variant: T669C, C1537T, G8078A, G12236A and G15077A. These results indicate that the new MitoChip platform is a rapid and valuable tool for identification of new mtDNA mutations in deafness.

Universal newborn hearing screening: a 27-month experience in the French region of Champagne-Ardenne.

OBJECTIVES: This article reports the creation of a Universal Newborn Hearing Screening (UNHS) program in a French region, Champagne-Ardenne, and the results of its first 27 months. MATERIALS AND METHODS: We introduced a UNHS program in all the Champagne-Ardenne maternities in order to screen all newborns in the region. We used a two-step strategy. The first test consists of automated transiently evoked otoacoustic emissions (TEOAE) and is performed before discharge by a nurse or a midwife. If TEOAE are absent in both ears (positive screening test), the baby is referred to the second test, which could be either TEOAE or automated auditory brainstem response (aABR) 15 days after discharge, by a physician in an outpatient clinic. If the retest is positive in both ears, the baby is referred to diagnostic tests in a reference centre. This procedure also applies to newborns in neonatal intensive care units but, in those cases, the first test procedure is aABR because of the higher incidence of auditory neuropathies in those units. UNHS data are recorded with the other neonatal screening tests in the Regional Neonatal Screening Center, which facilitates the follow-up of newborns. RESULTS: A total of 33 873 newborns were screened, which represents a coverage rate of 92.42%. In those babies, 33 431 had a negative first test and 429 were retested. There were 34 positive retests. Among those 34 children, 27 were actually deaf (0.08%). The median age at diagnosis was shortened from 17 months to 10 weeks. CONCLUSION: Those 27-month results demonstrate the validity of our UNHS program, which relies on the cooperation with maternities, an easy protocol and a strong follow-up procedure.

Surgical therapy in intractable benign paroxysmal positional vertigo.

OBJECTIVES: Benign paroxysmal positional vertigo (BPPV) is the most frequent vestibular disorder. Although it is easily cured with canal repositioning maneuvers for the majority of patients, it can be disabling in rare cases. For these patients, surgical solutions may be proposed. The aim of this article is to review the techniques used, the reported cases in the literature, and to discuss their indication in intractable BPPV. STUDY DESIGN: Literature review. MATERIALS AND METHODS: All the articles from 1972 to 2005 that discussed a specific surgical therapy in BPPV were reviewed. Many of them reported cases of operated patients and described original techniques. Some others are anatomic studies that discussed the two techniques used: singular neurectomy and posterior semicircular canal occlusion. RESULTS: Singular neurectomy (posterior ampullary nerve transsection) and posterior semicircular canal occlusion are the 2 specific techniques used in intractable BPPV surgery. The numbers of operated cases are 342 and 97, respectively. These small numbers indicate that the procedures are difficult and risk compromising hearing and that a very small population of patients require surgical treatment of BPPV. The operated cases have been decreasing since the early 1990s because of improved management in BPPV. This article summarizes the techniques and their results and proposes a currently recommended practice of surgical therapy in BPPV as well as new insights into intractable BPPVs' physiopathology.