Preoperative imaging in third molar surgery - A prospective comparison of X-ray-based and radiation-free magnetic resonance orthopantomography.

This study aimed to compare preoperative data relevant to third molar surgery based on radiographic orthopantomography (OPG) and orthopantomogram-like MR images (MR-OPG), using five different MR protocols. X-ray-based OPG and OPG-like MRI reconstructions from DESS, SPACE-STIR, SPACE-SPAIR, T1-VIBE-Dixon, and UTE sequences were acquired in 11 patients undergoing third molar surgery, using a 15-channel mandibular coil. Qualitative (image quality, susceptibility to artifacts, positional relationship, contact/non-contact of the inferior alveolar nerve (IAN), relationship to maxillary sinus, IAN continuity, root morphology) and quantitative (tooth length, retromolar distance, distance to the IAN, and distance to the mandible margin) parameters of the maxillary and mandibular third molars were assessed regarding inter-reader agreement and quantitative discrepancies by three calibrated readers. Radiation-free MR-OPGs generated within clinically tolerable acquisition times, which exhibited high image quality and low susceptibility to artifacts, showed no significant differences compared with X-ray-based OPGs regarding the assessment of quantitative parameters. UTE MR-OPGs provided radiographic-like images and were best suited for assessing qualitative preoperative data (positional relationship, nerve contact/non-contact, and dental root morphology) relevant to third molar surgery. For continuous and focal nerve imaging, DESS MR-OPG was superior. MR-OPGs could represent a shift towards indication-specific and modality-oriented perioperative imaging in high-risk oral and maxillofacial surgery.

The inferior alveolar nerve and its relationship to the mandibular canal.

Previous work on the mandibular canal, mental foramen, and mandibular foramen has focused on humans and some other non-primate mammals (with small sample sizes), but little work has investigated the mandibular canal and inferior alveolar nerve (IAN) across primates. However, it is important to understand the relationship between the IAN and mandibular canal due to the IAN's close relationship to the teeth and mastication, and thus dietary adaptations. While it is assumed that most bony canals within the skull grow around and form to pre-existing nervous structures, this relationship has never been validated for the IAN and mandibular canal. MicroCT scans of 273 individuals (131 females, 134 males, and 8 unknown sex) from 68 primate species and three mammalian outgroups, and diceCT scans of 66 individuals (35 females, 23 males, and 8 unknown sex) from 33 primate species and the same mammalian outgroups were used to create 3D models of the IAN and mandibular canal from which cross-sectional areas were taken at various points on the structures. Using qualitative descriptions, phylogenetic generalized least squares analysis, and phylogenetic ANOVAs, we were able to establish three main conclusions: (1) the mandibular canal is most often not a defined canal within the mandible of primates, (2) when the canal can be identified, the IAN does not comprise most of the space within, and (3) there are significant relationships between the IAN and the corresponding canals, with most showing isometry and the mental foramen/nerve showing negative allometry.

Mandibular Canal Branching Assessed With Cone-Beam Computed Tomography.

This study aimed to evaluate the prevalence and type of mandibular canal branching in a sample of the Iranian population through cone-beam computed tomography (CBCT) images. This cross-sectional study was performed on CBCT records of 300 patients (112 males and 188 females; mean age 30.14 ± 10.96 y). The presence of mandibular canal branch (MCB) was evaluated by reconstructing multiple panoramic views and buccolingual cross-sections, according to Naitoh's classification. The prevalence of MCB, the type of MCB, and the demographic information of all patients were recorded. The maximum number of branching and the maximum type of branching were also registered for each patient. Mandibular canal branching was observed in 131(43.7%) of 300 CBCT images without side or sex differences ( P > 0.05). The most frequent type was dental, followed by the retromolar, forward, and buccolingual types, respectively. There was a statistically higher frequency of retromolar canal in females than in males (odds ratio: 1.14 ± 4.25; P = 0.013). About 46% of patients with MCB had more than one accessory canal and 29% displayed more than one type of MCB. The coincidence of dental and retromolar canals in a patient was the most prevalent combination. Considering the relatively high prevalence of MCB (43.7%), it is recommended to keep in mind the possibility of anatomical variations of the inferior alveolar nerve during dental procedures to avoid postsurgical complications. The high possibility of observing multiple numbers and types of branching in the patients should also be considered during preoperative assessments.

Lingual nerve impairment/injury after retrieval of the displaced mandibular third molar into the floor of the mouth.

Retrieval of the displaced mandibular third molar in the floor of the mouth is challenging as the lingual nerve is always at risk of injury. However, there are no available data to show the incidence of the injury caused by the retrieval. The goal of this review article is to provide the incidence of the iatrogenic lingual nerve impairment/injury caused by the retrieval based on the review of the existing literature. The retrieval cases were collected with the search words below using PubMed, Google Scholar, and CENTRAL Cochrane Library database on October 6, 2021. A total of 38 cases of lingual nerve impairment/injury in 25 studies were eligible and reviewed. Temporary lingual nerve impairment/injury due to retrieval was found in six cases (15.8%) and all recovered between three to six months after retrieval. General anaesthesia and local anaesthesia were used for retrieval in three cases each. The tooth was retrieved using a lingual mucoperiosteal flap in all six cases. The permanent iatrogenic lingual nerve impairment/injury due to retrieval of the displaced mandibular third molar is considered extremely rare as long as the appropriate surgical approach is chosen based on surgeons' clinical experience and anatomical knowledge.

Assessment of the prevalence and length of the anterior and caudal loops of the mental nerve as anatomical variants of exiting the mandible at the mental foramen using cone-beam computed tomography: a systematic review and meta-analysis.

OBJECTIVES: This systematic review aimed to identify the studies that performed cone-beam computed tomography analysis of the prevalence and length of the anterior loop (AL) and caudal loop (CL) of the mental nerve. MATERIALS AND METHODS: An electronic database search was performed across PubMed, EMBASE, Web of Science, Scopus, the Cochrane library, and Google Scholar. Original studies reporting the frequency and length of the AL and CL were selected. Qualitative synthesis and meta-analysis were then conducted to assess the prevalence and length of the AL and CL and their associations with age, gender, sides, and dentition status. RESULTS: A total of 21 studies were included in this review. The pooled prevalence of the AL (95% confidence interval) of the mental nerve at the patient and side level was 51% (31-71%) and 53% (37-69%) while the mean anterior loop length was 2.08 (1.46-2.70) mm. The pooled prevalence of the CL and mean caudal loop length were 100% and 4.73 (3.44-6.01) mm. No significant associations were found between the prevalence and length of the AL and CL and age, gender, sides, and dentition status. CONCLUSIONS: Overall, the pooled prevalence and mean length of AL of the mental nerve varied among different populations while CL seems to be a constant anatomical landmark with a longer CL than AL. CLINICAL RELEVANCE: Surgeons performing inter-foraminal oral surgeries like dental implant placement and genioplasty should be aware of the possible distance of the AL and CL to avoid iatrogenic mental nerve injury.

Novel strategy to predict high risk of inferior alveolar nerve injury during extraction of lower third molars based on assessment of computed tomographic images of multiple anatomical features.

Preoperative assessment is essential to prevent inferior alveolar nerve (IAN) injury during surgical extraction of the lower third molar (LM3). Here, we aimed to establish an assessment system to predict IAN injury during surgical extraction of the LM3. We conducted a retrospective cohort study on 115 patients diagnosed as 'high-risk' based on our previous risk assessment method involving three anatomical features of the inferior alveolar canal using computed tomographic (CT) images. We evaluated the occurrence of neurosensory impairment in these high-risk patients, and its association with novel anatomic features based on CT images. Neurosensory impairments were observed in 19 patients (16.5%). The inferior alveolar canal major diameter (p < 0.0001) and lingual bone thickness (p = 0.0039) were significantly associated with the occurrence of neurosensory impairment during LM3 extraction. Receiver operating characteristic curves were used to determine cut-off values of these quantitative factors to specifically predict IAN injury. Preoperative risk assessment with quantitative factors based on anatomical features observed on CT images may facilitate more appropriate surgical planning for patients at a high risk of IAN injury.

Variant innervation of the mylohyoid muscle by the lingual nerve.

The nerve to mylohyoid muscle supplies the mylohyoid and the anterior belly of the digastric muscles, with terminal sensory branches that might innervate the submental skin and mandibular teeth. The nerve to mylohyoid muscle typically originates from the posterior surface of the inferior alveolar nerve right before entering the mandibular foramen. In rare cases, the nerve to mylohyoid muscle arises from the lingual nerve. The variations of the nerve to mylohyoid muscle might have led to failure of an inferior alveolar nerve blockade. During the routine dissection of a cadaveric head, a rare case was identified where the nerve to mylohyoid muscle had origins from both the inferior alveolar and lingual nerves. This case is reviewed and salient literature reviewed.

Tomographic evaluation of the mandibular nerve in the mental region and its surgical implications: a cross-sectional study.

The aim of this study was to evaluate the prevalence and length of the anterior loop (AL) of the inferior alveolar nerve, nerve emergence from the mental foramen, and prevalence of sensory disorders after implant placement in the interforaminal region. Four hundred and fifty hemimandibles (225 patients) were evaluated using cone beam computed tomography and panoramic radiographs. Information on the presence of sensory disorders was obtained from the medical records. AL prevalence was 13.6% and mean AL length was 1.25 mm. The false-negative rate for the identification of the AL using panoramic radiography was 58.6%. Straight nerve emergence from the mental foramen was the most prevalent (62.7%), followed by anterior (21.8%) and posterior (15.6%) emergence. The incidence of sensory disorders was 4.4%, and 1.1% were related to the presence of the AL. When implants were placed within the planned distance of the mental foramen or further, 1.2% had sensory problems associated with the presence of the mandibular incisive canal. In cases of distances smaller than planned, 12.9% had sensory alterations. Only five (1.1%) had the AL, with a length between 0 and 4.5 mm. However, in four cases, the planned distance was respected and, even so, there was a sensory disorder. Posterior nerve emergence from the mental foramen was associated with a higher prevalence of AL.

The neurosensory deficit of inferior alveolar nerve following bilateral sagittal split osteotomy: a prospective study.

OBJECTIVES: Investigation in Saudi Arabia or the Arab Gulf States to assess the unfavorable impacts of the bilateral sagittal split osteotomy (BSSO) is non-existent, so questions have been raised about the success rate of this operation and the frequency of unwilling outcome. To address these worries, we directed a case series study to evaluate the hypoesthesia, a type of neurosensory deficit (NSD) of the inferior alveolar nerve (IAN) after BSSO, and if the hypoesthesia outcome will improve if the surgeries performed by a single surgeon. PATIENTS AND METHODS: This was a prospective case series study for the patient who underwent BSSO in a medical complex that is considered one of the largest in Saudi Arabia (Riyadh). The inclusion criteria include patient aged 18-40 years, any gender, and American Society of Anesthesiologists (ASA) class I. They will undergo BSSO for either mandibular, retrognathia, prognathic, or to follow the maxilla. The outcome will be measured after evaluating the neurosensory by four means light touch (LT), pinprick (PP), 2-point discrimination (2PD), and thermal sensations (TT) in four repeated measurements (preoperatively, 1 week, 1 month, 3 months postoperatively) as the primary outcome. Other confounding factors were the secondary outcome (age, gender, visualization of the I.A.N, the type of mandibular movement, split favorability, mandibular canal location, and patient reports about paresthesia or dysesthesia on any given side); these data analyses were carried out using SPSS ver. 25 data processing software. RESULTS: The nerve was visible in 93% of cases. During the operation, none of the nerves was transected. Hypoesthesia on the first follow-up was 94% of cases for LT, 92% for PP, 82% for TT, and 100% for the 2PD. On the last follow-up, the patients still had hypoesthesia for the LT 51%, PP 35%, TT41%, and 2PD 55%; age and sex did not significantly affect hypoesthesia outcomes. Nerve visibility and inferior alveolar nerve canal (IAC) distance did not influence the results. The level of confidence for all tests was set at p < 0.05. CONCLUSIONS: The 2PD sensation was the most affected sense on the last visit, and the right side of the chin and lower lip was affected most both on early and long-term follow-up due to several reasons. A 3-month period was enough as a recovery time to restore 100% of neurological sensation for 45% of the sample, which is similar to several studies in the literature. A single surgeon did not show superior result compared to two surgeons' literature papers. Advancement movement was associated with a high percentage of hypoesthesia.

The Assessment of Neurosensory Disturbance Following Bilateral Sagittal Split Osteotomy With Subjective and Three-Dimensional Evaluation.

PURPOSE: Inferior alveolar neurosensory disturbance (IAND) is the most common complication of bilateral sagittal split osteotomy (BSSO). The aim of the present study was to evaluate IAND with subjective tests postoperatively and assess the relationship between three-dimensional measurements of the mandibular canal (MC) and IAND. METHODS: Eighteen patients (Mean age: 24.05 ±â€Š5.85 years) treated with BSSO were retrieved from the archive. Subjective tests (light touch, tactile sensitivity, 2-point discrimination, brush-stroke directional discrimination, sharp/blunt discrimination, dental vitality, questionnaire) and three-dimensional measurements related to MC and fixation screws were done postoperatively (on average 20.43 ±â€Š8.76 months after surgery). Statistical significance was set at P  < 0.05. RESULTS: Subjective test results were found compatible with each other except brush-stroke directional discrimination test. According to the questionnaire, IAND was apparent in all patients immediately after surgery, and recovery after 1 to 2 years was statistically significant ( P  < 0.05). Preoperative ramus width, medial and lateral cancellous bone lengths, the decrease in MC length, and the presence of screw in MC were not related to IAND ( P  < 0.05). CONCLUSIONS: There is a high incidence of IAND following BSSO, and the subjective tests are efficient to evaluate the disturbance. Spontaneous recovery of the nerve occurs during the follow-up periods. Instead of preoperative measurements of bone thickness, MC length, and the position of fixation screws, the surgical procedure seems to be more important in IAND occurrence.

Inervación suplementaria de la mandíbula y sus Implicancias clínicas: revisión narrativa / Supplemental innervation of the mandible and it´s clinical implications: narrative review

RESUMEN: En condiciones normales, la mandíbula y sus estructuras anatómicas (dientes, musculatura, piel), son inervadas por los ramos de la tercera división del nervio trigémino (nervio mandibular), sin embargo, existen reportes que evidencian inervación suplementaria de los dientes inferiores y la zona del ángulo mandibular. Lo último podría ser responsable del fracaso del bloqueo nervioso con anestesia local. El objetivo principal de esta investigación fue revisar artículos que describen la participación de otros nervios como el milohioideo y los ramos superficiales del plexo cervical, los cuales pueden ingresar a la mandíbula a través de forámenes ubicados a lo largo de su arquitectura. Para esto, se realizó una revisión narrativa de la literatura científica, en inglés y español, desde el año 1971 hasta el año 2019, utilizando las plataformas digitales PubMed, EBSCO, Cochrane library, Scielo y Google Scholar, literatura gris y además de una búsqueda manual. Acorde a los resultados de la revisión, se confirma la existencia de fracasos de técnicas anestésicas mandibulares debido a la inervación accesoria de la mandíbula y de los dientes inferiores, donde los tres principales nervios revisados tienen incidencia en este postulado. Finalmente se plantea un orden de ejecución para realizar la infiltración de anestésico local en la mandíbula para lograr un bloqueo exitoso durante los procedimientos odontológicos que la requieran.

SUMMARY: Under normal conditions, the mandible and its anatomical structures (teeth, muscles, skin) are innervated by the branches of the third division of the trigeminal nerve (mandibular nerve), however, there are reports that show supplementary innervation of the lower teeth and the mandibular angle area. The latter could be responsible for the failure of the nerve block under local anesthesia. The main objective of this research; is to review articles that describe the participation of other nerves such as the mylohyoid nerve, and the superficial branches of the cervical plexus, which can enter the mandible through foramina located along its architecture. For this, a narrative review of the scientific literature was carried out, in English and Spanish, from 1971 to 2019, using the digital platforms PubMed, EBSCO, Cochrane library, Scielo and Google Scholar, gray literature and in addition to a search Handbook. According to the results of the review, the existence of the failures of the mandibular anesthetic techniques due to the accessory innervation of the mandible and the lower teeth is confirmed, where the three main nerves reviewed have an impact on this postulate. In conclusion, an order of execution is proposed to perform local anesthetic infiltration into the jaw to achieve a successful block during dental procedures that require it.

Factors affecting root migration after coronectomy of the mandibular third molar.

ABSTRACT: Nerve injury especially inferior alveolar nerve (IAN) is the one of the complications that occur when the mandibular third molar (M3) is extracted and in case of high risk patients, coronectomy might be an alternative to tooth extraction. The purpose of this retrospective study was to analyze root migration and its influencing factors at 6 months after coronectomy in both 2- and 3-dimensions using periapical view and cone-beam computed tomography (CBCT). We analyzed 33 cases of root remnant after coronectomy and measured the amount of migration in CBCT. The following factors that could possibly affect root migration were also analyzed: age, gender, number of M3 roots, shape of M3s, Pell, and Gregory classification, mesiodistal (MD) angulation, buccolingual (BL) angulation, contact point with the second molar, root curvature, and complete removal of the coronal portion. Migration of greater than 2 mm was found in 64% of the roots in the 2-dimensional (2D) analysis, and the average root migration was 4.11 mm in the 3-dimensional (3D) analysis. The factors affecting migration were the root morphology, complete removal of the coronal portion, impaction depth, and MD angulation in the 2D analysis, and MD and BL angulation in the 3D analysis. Ensuring sufficient space for root migration especially considering angulation, depth and complete removal of the coronal portion might be important factors after coronectomy of the M3. Root remnant after coronectomy of M3 may migrate in young patients who has sufficient empty coronal space and this may reduce the nerve damage by the separation of IAN and M3.

Mandibular canal versus inferior alveolar canal: A Delphi study.

The general principles of anatomical terminology indicate that the "mandibular canal" should be named the "inferior alveolar canal" as it accommodates the inferior alveolar neurovascular bundles. Therefore, we performed a Delphi study to evaluate the current understanding and use of the terminology in different geographical regions and areas of expertise and to determine the appropriate terminology for this bony canal. A Delphi panel was formed and questions sent and answered via email about: field of expertise (anatomy, oral surgery/oral and maxillofacial (OMF) surgery, oral radiology/OMF radiology, plastic surgery, ENT surgery, or dentistry with the exception of oral/OMF surgery and oral/OMF radiology), years of experience in the field of expertise, country currently working in, "what is the name of the bony canal that contains the inferior alveolar neurovascular bundle," and "what should the structure above be called, in general?" A total of 52 participants responded to the questionnaire. Half or more of the experts in anatomy, oral/OMF surgery, and ENT/plastic surgery considered "mandibular canal" to be the most appropriate name for this bony canal. In contrast, more than half of all experts in oral/OMF radiology and dentistry, that is, most fields of dentistry, considered "either mandibular canal or inferior alveolar canal" to be the appropriate name. The results of the Delphi study and general principles suggest that an alternative term for the "mandibular canal" should be "inferior alveolar canal."

Effects of exogenous nerve growth factor on the expression of BMP-9 and VEGF in the healing of rabbit mandible fracture with local nerve injury.

BACKGROUND: Mandibular fracture healing is a complex process involving nerves and growth factors. Nerve growth factor (NGF) not only facilitates the maintenance of sympathetic neurite growth but also stimulates other growth factors that can promote the essential osteogenesis and angiogenesis for fracture healing. Therefore, it is necessary to analyze the combined effects of NGF, bone morphogenic protein-9 (BMP-9), and vascular endothelial growth factor (VEGF) to accelerate the healing of mandible fractures. METHODS: The models of mandible fracture with local nerve injury established in 48 rabbits were randomly divided into nerve growth factor group (NGF group), gelatin sponge group (GS group), blank group, and intact group. The recovery of nerve reflex was assessed by observing the number of rabbits with lower lip responses to acupuncture. The fracture healing was observed with visual and CBCT, and then callus tissues from the mandibular fracture area were collected for hematoxylin and eosin (HE) staining observation, and the expression of BMP-9 and VEGF in callus at different stages was detected by quantitative real-time PCR (qRT-PCR). RESULTS: Needling reaction in the lower lip showed the number of animals with nerve reflex recovery was significantly higher in the NGF group than that in the GS and blank groups at the 2nd and 4th weeks after the operation. The combined results of macroscopic observation, CBCT examination, and histological analysis showed that a large number of osteoblasts and some vascular endothelial cells were found around the trabecular bone in the NGF group and the amount of callus formation and reconstruction was better than that in the GS group at the 2nd week after the operation. The qRT-PCR results indicated that the expression levels of BMP-9 and VEGF in the four groups reached the highest values at the 2nd week, while the expression levels of both in the NGF group were significantly higher than that in the GS group. CONCLUSION: The exogenous NGF could accelerate the healing of mandible fractures. This work will provide a new foundation and theoretical basis for clarifying the mechanism of fracture healing, thereby promoting fracture healing and reducing the disability rate of patients.

Nerve growth factor-chondroitin sulfate/hydroxyapatite-coating composite implant induces early osseointegration and nerve regeneration of peri-implant tissues in Beagle dogs.

BACKGROUND: Osseointegration is the premise of the chewing function of dental implant. Nerve growth factor (NGF), as a neurotrophic factor, can induce bone healing. However, the influence of NGF-chondroitin sulfate (CS)/hydroxyapatite (HA)-coating composite implant on the osseointegration and innervations is still not entirely clear. MATERIALS AND METHODS: NGF-CS/HA-coating composite implants were prepared using the modified biomimetic method. The characteristics of NGF-CS/HA-coating implants were determined using a scanning electron microscope. After NGF-CS/HA-coating implants were placed in the mandible of Beagle dogs, the early osseointegration and innervation in peri-implant tissues were assessed through X-ray, Micro-CT, maximal pull-out force, double fluorescence staining, toluidine blue staining, DiI neural tracer, immunohistochemistry, and RT-qPCR assays. RESULTS: NGF-CS/HA-coating composite implants were made successfully, which presented porous mesh structures with the main components (Ti and HA). Besides, we revealed that implantation of NGF-CS/HA-coating implants significantly changed the morphology of bone tissues and elevated maximum output, MAR, BIC, and nerve fiber in the mandible of Beagle dogs. Moreover, we proved that the implantation of NGF-CS/HA-coating implants also markedly upregulated the levels of NGF, osteogenesis differentiation, and neurogenic differentiation-related genes in the mandible of Beagle dogs. CONCLUSION: Implantation of NGF-CS/HA-coating composite implants has significant induction effects on the early osseointegration and nerve regeneration of peri-implant tissues in the mandible of Beagle dogs.

Inferior alveolar nerve reconstruction in extensive mandibular resection: Technical notes.

The inferior alveolar nerve (IAN) is a sensitive branch of the mandibular nerve innervating the lower lip, the chin, the buccal mucosa and the teeths. Lesions of the IAN are reported to occur in the 64,4% of maxillo-facial procedures, leading to anesthesia, hypoestesia and/or neurogenic discomfort. An extensive segment of the nerve can be moreover removed during mandibular resection for benign or malignant pathologies. Nervous grafts can be used in these cases to restore the nerve continuity. In order to optimize the procedure and to allow a concomitant mandibular osseous reconstruction, the Authors identified several standardized steps. The technique described allows to perform confortable and safe nervous anastomoses and to reduce the risk of damage and tension during the flap insetting phases.

Anatomic Variations From 120 Mental Nerve Dissections: Lessons for Transoral Thyroidectomy.

BACKGROUND: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a promising technique for eliminating a neck incision. A new risk of TOETVA is the potential for injury to the mental nerves during placement of three oral endoscopic ports. A better understanding of the variations in mental nerve anatomy is needed to inform safer TOETVA technique. MATERIALS AND METHODS: We performed 120 dissections of mental nerve branches exiting the mental foramen in 60 human cadavers. Anatomic distances and relationships of the foramen to the midline were evaluated. Mental nerve branching patterns were studied and compared with previously reported classification systems to determine surgical safe zones free of nerve branches. RESULTS: The mean midline-to-mental foramen distance was 29.2 ± 3.3 mm, with high variability across individuals (18.8-36.8 mm). There were differences in this distance between the left and right foramina (29.8 ± 3.2 versus 28.8 ± 3.3 mm, P = 0.03). All mental nerve branches exiting the mental foramen distributed medially. The branching patterns were classified into eight distinct categories, three of which are previously undescribed. One of these novel patterns, occurring in 9.2% of cases, had a dense and wide clustering of branches traveling toward the midline. CONCLUSIONS: The location of the mental foramen and mental nerve branching patterns demonstrate high variability. To avoid mental nerve injury in TOETVA, we identify a safe zone for lateral port placement lateral to the plane of the mental foramen. Placement and extension of the middle port incision should proceed with caution, as clustering of mental nerve branches in this area can frequently be present.

Neural regulation in tooth regeneration of Ambystoma mexicanum.

The presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nerve-dependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration. The presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nervedependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration.