The trend of dental check-up and prevalence of dental complications following the use of bone modifying agents in patients with metastatic breast and prostate cancer: analysis of data from the Korean National Health Insurance Service.

BACKGROUND: Bone-modifying agents (BMA) are key components in the management of cancer patients with bone metastasis. Despite their clinical benefits, the use of BMA is associated with dental adverse events (AEs) including medication-related osteonecrosis of the jaw (MRONJ). This study investigated the frequency of dental surveillance before BMA treatment and the prevalence of dental AEs including MRONJ, after BMA treatment in patients with bone metastasis from breast and prostate cancer using data from the national health insurance system. METHODS: Data, including age, cancer diagnosis, administered BMA, and dental AEs during cancer treatment, of patients with bone metastasis from breast and prostate cancer who received at least one infusion of BMA between 2007 and 2019 were extracted from the Korean National Health Insurance Service (KNHIS) dataset. RESULTS: Of the 15,357 patients who received BMA, 1,706 patients (11.1%) underwent dental check-ups before BMA treatment. The proportion of patients receiving dental check-up increased from 4.4% in 2007 to 16.7% in 2019. Referral to dentists for a dental check-up was more active in clinics/primary hospitals than general/tertiary hospitals, and medical doctors and urologists actively consulted to dentists than general surgeons, regardless of the patient's health insurance status. After BMA treatment, 508 patients (3.8%) developed dental AEs, including abscess (42.9%), acute periodontitis (29.7%), acute pericoronitis (14.9%), and MRONJ (12.5% of dental AEs cases, 0.5% of total BMA treated patients). CONCLUSIONS: Considering the long treatment period in patients with metastatic cancer, coordination between dentists and oncologists is necessary to ensure appropriate dental management before the initiation of BMA.

Can medication-related osteonecrosis of the jaw be attributed to specific microorganisms through oral microbiota analyses? A preliminary study.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) can cause significant pain and loss of aesthetics and function if not treated properly. However, diagnosis still relies on detailed intraoral examinations and imaging. Prognosis varies even among patients with similar stages or conditions of MRONJ, emphasizing the need for a deeper understanding of its complex mechanisms. Thus, this study aimed to identify the oral microbiota of patients with MRONJ. METHODS: This single-center prospective cohort study included patients with confirmed MRONJ who visited the Department of Oral and Maxillofacial Surgery at Yonsei University Dental Hospital between 2021 and 2022. Oral swab samples were collected from the affected and unaffected sides of each patient. The composition and enumeration of the microbial communities were analyzed, and the diversity was compared to verify ecological changes in the groups using a next-generation sequencing-based 16S metagenomic analysis. A statistical analysis was performed using Wilcoxon signed-rank test with SPSS version 22, and values of P less than 0.05 were considered statistically significant. RESULTS: The final study sample included 12 patients. The mean age was 82.67 ± 5.73 (range, 72-90) years. Changes in microbial composition were observed at different taxonomic levels (phylum, genus, and species). The identified microorganisms were commonly associated with periodontitis, gingival disease, and endodontic infection, suggesting a multifactorial etiology of MRONJ. CONCLUSIONS: Although this study is based on a small number of cases, it shows that MRONJ is not caused by a specific microorganism but can rather be caused by a variety of factors. By addressing these findings in large-scale studies, the significance of oral microbiome in pathogenesis can be further elucidated and can facilitate the development of effective therapeutic interventions for patients with MRONJ.

The assessment of halitosis with a new screening tool in medication-related osteonecrosis of the jaw.

OBJECTIVES: This study aimed to identify the levels of halitosis in patients with Medication-related osteonecrosis of the jaw (MRONJ) and osteoporosis and to suggest a new MRONJ screening method using halitosis measurement. MATERIALS AND METHODS: From October 2019 to April 2023, participants aged 19 years or older without periodontal disease were selected. Seventy-five participants, 25 in each group, were divided into an MRONJ group, an osteoporosis group without MRONJ, and a control group without osteoporosis and not taking osteoporosis drugs or antibiotics. Each participant underwent halitosis assessment twice using an exhaled breath analyzer to measure halitosis twice by blowing a straw for 1 min. Measured concentrations of hydrogen, hydrogen sulfide, and methyl mercaptan were compared between groups. RESULTS: Data from 22 patients in the MRONJ group, 25 in the osteoporosis group, and 25 in the control group were analyzed. The concentrations of hydrogen sulfide and methyl mercaptan were significantly higher in the MRONJ group than in the other groups, but the concentrations of hydrogen did not differ between the groups. When comparing the concentrations of hydrogen sulfide and methyl mercaptan in osteoporosis patients and solid cancer patients in the MRONJ group, there was a significant difference in hydrogen sulfide concentration, but there was no significant difference in methyl mercaptan. CONCLUSIONS: Quantifying the level of halitosis can be used to screen for MRONJ in patients taking bisphosphonates, such as patients with osteoporosis, prostate cancer, and breast cancer. CLINICAL RELEVANCE: MRONJ is accompanied by bad breath, and the concentrations of hydrogen sulfide and methyl mercaptan are associated with MRONJ.

Automated deep learning for classification of dental implant radiographs using a large multi-center dataset.

This study aimed to evaluate the accuracy of automated deep learning (DL) algorithm for identifying and classifying various types of dental implant systems (DIS) using a large-scale multicenter dataset. Dental implant radiographs of pos-implant surgery were collected from five college dental hospitals and 10 private dental clinics, and validated by the National Information Society Agency and the Korean Academy of Oral and Maxillofacial Implantology. The dataset contained a total of 156,965 panoramic and periapical radiographic images and comprised 10 manufacturers and 27 different types of DIS. The accuracy, precision, recall, F1 score, and confusion matrix were calculated to evaluate the classification performance of the automated DL algorithm. The performance metrics of the automated DL based on accuracy, precision, recall, and F1 score for 116,756 panoramic and 40,209 periapical radiographic images were 88.53%, 85.70%, 82.30%, and 84.00%, respectively. Using only panoramic images, the DL algorithm achieved 87.89% accuracy, 85.20% precision, 81.10% recall, and 83.10% F1 score, whereas the corresponding values using only periapical images achieved 86.87% accuracy, 84.40% precision, 81.70% recall, and 83.00% F1 score, respectively. Within the study limitations, automated DL shows a reliable classification accuracy based on large-scale and comprehensive datasets. Moreover, we observed no statistically significant difference in accuracy performance between the panoramic and periapical images. The clinical feasibility of the automated DL algorithm requires further confirmation using additional clinical datasets.

Comparison of detection performance of soft tissue calcifications using artificial intelligence in panoramic radiography.

Artificial intelligence (AI) is limited to teeth and periodontal disease in the dental field, and is used for diagnosis assistance or data analysis, and there has been no research conducted in actual clinical situations. So, we created an environment similar to actual clinical practice and conducted research by selecting three of the soft tissue diseases (carotid artery calcification, lymph node calcification, and sialolith) that are difficult for general dentists to see. Therefore, in this study, the accuracy and reading time are evaluated using panoramic images and AI. A total of 20,000 panoramic images including three diseases were used to develop and train a fast R-CNN model. To compare the performance of the developed model, two oral and maxillofacial radiologists (OMRs) and two general dentists (GDs) read 352 images, excluding the panoramic images used in development for soft tissue calcification diagnosis. On the first visit, the observers read images without AI; on the second visit, the same observers used AI to read the same image. The diagnostic accuracy and specificity for soft tissue calcification of AI were high from 0.727 to 0.926 and from 0.171 to 1.000, whereas the sensitivity for lymph node calcification and sialolith were low at 0.250 and 0.188, respectively. The reading time of AI increased in the GD group (619 to 1049) and decreased in the OMR group (1347 to 1372). In addition, reading scores increased in both groups (GD from 11.4 to 39.8 and OMR from 3.4 to 10.8). Using AI, although the detection sensitivity of sialolith and lymph node calcification was lower than that of carotid artery calcification, the total reading time of the OMR specialists was reduced and the GDs reading accuracy was improved. The AI used in this study helped to improve the diagnostic accuracy of the GD group, who were not familiar with the soft tissue calcification diagnosis, but more data sets are needed to improve the detection performance of the two diseases with low sensitivity of AI.

Identifying the course of the greater palatine artery using intraoral ultrasonography: cohort study.

AIMS: The greater palatine artery (GPA) is one of the most important anatomical structure for free gingival grafts or connective-tissue grafts during soft tissue surgery for dental implants. Several studies have identified the approximate location of the GPA, but it is impossible to detect its exact location during surgery due to large variability between individuals. The authors, therefore, investigated the course of the GPA using intraoral ultrasonography to determine the feasibility of using real-time nonionizing ultrasonography for implant surgery. MATERIALS AND METHODS: This study included 40 healthy young participants. The courses of the GPA were identified using intraoral ultrasound probes from the first premolar to the second molar. The distance from the gingival margin to the GPA (GM-GPA) and the depth of the palatal gingiva from the GPA (PG-GPA) were measured by two independent examiners. Measurements were analyzed statistically, and interexaminer reliability was determined. RESULTS: The distance of the GM-GPA and the mean depth of the PG-GPA were 14.8 ± 1.6 mm and 4.10 ± 0.51 mm (mean ± SD), respectively. GM-GPA decreased when the GPA ran from the second molar to the first molar, and GM-GPA was significantly shorter in females (P < 0.05). PG-GPA increased when the GPA ran to the posterior teeth. Interexaminer measurement agreements were excellent, with intraclass correlation coefficient values of 0.983 and 0.918 for GM-GPA and PG-GPA, respectively. CONCLUSIONS: Using an intraoral ultrasound probe, real-time GPA tracking is possible, which is expected to help reduce the possibility of bleeding during surgery.

Assessment of Real-Time Active Noise Control Devices in Dental Treatment Conditions.

Dental clinics are exposed to various uncomfortable noises. The aim of this study was to quantify the effectiveness of active noise control devices in dental treatment conditions. Two types of commercial headsets (Airpods Pro, QC30) and two types of dental headsets (Alltalk, Quieton Dental) were used for the experiment. Three sounds (high-speed handpiece, low-speed handpiece, and suction system) were measured at three different distances from the dental teeth model, typodont. The distances of 10, 40, and 70 cm reflected the positions of the patient, assistant, and practitioner's ears, respectively. Sound analysis was performed, and the significance of differences in the maximum noise level using each device was determined with the Kruskal−Wallis test. Dental noise was characterized by the peak in sound pressure level (SPL) at 4−5 kHz and >15 kHz frequencies. The commercial headsets efficiently blocked 1 kHz and 10 kHz of noise. The dental headsets efficiently reduced 4−6 and >15 kHz noise. Quieton had the highest maximum SPL in all situations and positions among the four devices. For a better dental clinic, however, active noise control devices more suitable for the characteristics of dental noise should be developed.

Foreign body aspiration and ingestion in dental clinic: a seven-year retrospective study.

Background: This retrospective study investigated the incidence rate of accidental foreign body aspiration and ingestion according to patient sex, age, and dental department. This study aimed to verify whether the incidence rate is higher in geriatric than in younger patients and whether it is different among dental departments. Methods: Accidental foreign body aspiration and ingestion cases were collected from electronic health records and the safety report system of Yonsei University Dental Hospital from January 2011 to December 2017. The collected data included patients' age, sex, medical conditions, treatment procedures, and foreign objects that were accidentally aspirated or ingested. The incidence rate was calculated as the number of accidental foreign body aspirations and ingestions relative to the total number of patient visits. Differences depending on the patients' sex, age, and dental department were statistically identified. Results: There were 2 aspiration and 37 ingestion cases during the 7-year analysis period. The male to female incidence ratio was 2.8:1. The incidence rate increased with age and increased rapidly among those aged 80 years or older. Seven of the 37 patients with accidental foreign body ingestion had intellectual disability, Lou Gehrig's disease, dystonia, or oral and maxillofacial cancer. The incidence rate was highest in the Predoctoral Student Clinic and the Department of Prosthodontics. The most frequently swallowed objects were fixed dental prostheses and dental implant components. Conclusion: The incidence rate of accidental foreign body aspiration and ingestion differed according to patient sex, age, and dental department. Dental practitioners must identify high-risk patients and apply various methods to prevent accidental foreign body aspiration and ingestion in dental clinics. Inexperienced practitioners should be particularly careful.

Qualitative focus group interview study of communication between patients, dentists and physicians for efficient osteonecrosis of the jaw practices.

OBJECTIVES: To investigate problems and the current status of existing methods of communication between patients, dentists and physicians for the prevention and treatment of medication-related osteonecrosis of the jaw (MRONJ). DESIGN: A focus group interview study with a descriptive design using qualitative content analysis of transcripts. SETTING: Secondary care in Korea. PARTICIPANTS: 3 patient groups and 4 health professional groups in a total of 32 participants including patients with osteoporosis or bone metastasis, dentists and physicians. RESULTS: This study revealed that patients lacked medical knowledge of osteoporosis drugs, whereas dentists and physicians lacked each other's expertise. All patients reported undergoing dental treatments during the osteoporosis drug treatment, but dentists and physicians had different MRONJ experiences depending on their work setting in primary or secondary care. Patients expressed dissatisfaction with the current system of communication with health professionals via letter as they found this to be a slow process. Dentists and physicians reported the need for effective communication because they felt defensive when sending and receiving medical consults. CONCLUSIONS: Despite the low incidence of MRONJ among patients with osteoporosis, it is difficult to treat; thus, it is necessary to inform dentists, physicians and patients about the importance of MRONJ prevention. To this end, close communication among all involved stakeholders about osteoporosis drugs is required.

Orthodontic Extrusion of Mandibular Third Molar With a Miniscrew and Cross-Arch Elastic.

Sensory dysfunction is the most serious complication that occurs after extracting lower third molars in close proximity to the inferior alveolar nerve (IAN). Even experienced surgeons have difficulties in avoiding nerve damage when the root is anatomically adjacent to the nerve canal. A useful method for reducing nerve damage during extraction is to perform orthodontic extrusion, in which the distance between the nerve and the root increased after applying an orthodontic force on the third molar while extruding the tooth. Here, we report the case of a 37-year-old female who presented with a partially erupted left lower third molar and risk of IAN nerve damage because of close anatomical proximity between the nerve and root. She underwent extraction using a miniscrew placed in the maxilla and a routine orthodontic mechanism using a cross-arch elastic band that induced a 3-mm vertical eruption in the impacted third molar without using complex orthodontic devices. In addition, tilting the dental axis to the lingual side resolved the proximity between the IAN and the tooth, thereby allowing extraction to proceed without major complications.

Mucormycosis in the Jaw: A Report of 2 Cases and Literature Review.

Mucormycosis is a rare fungal infection with high morbidity and mortality and a very poor prognosis. However, aggressive medical and surgical management can result in survival rates exceeding 80%. The most common sites involved in mucormycosis infection are the sinus, lung, skin and soft tissues, gastrointestinal system, central nervous system, and rarely the mandible. Systemic risk factors for mucormycosis are diabetes mellitus (DM), neutropenia, corticosteroid use, hematologic malignancies, organ transplantation, metabolic acidosis, deferoxamine use, and advanced age. Local risk factors are a history of trauma, burns, surgery. We report on two patients with mucormycosis of the jaw. While one case presented as mucormycois involving the maxillary sinus in a patient with uncontrolled DM, the other was a rare case of mandibular mucormycosis in a patient with acute myeloid leukemia.

Effect of teriparatide on early sinus graft healing in the ovariectomized rabbit.

OBJECTIVES: The purpose of this study was to determine the effect of administering intermittent parathyroid hormone 1-34 [teriparatide, (PTH)] on the maxillary sinus lift and bone grafting in osteoporotic rabbits induced by ovariectomy and glucocorticoid. MATERIALS AND METHODS: Ovariectomies were performed on 20 female New Zealand white rabbits that were randomly divided into two groups: (a) the PTH group (n = 10), in which 10 µg kg-1  day-1 PTH was injected subcutaneously 5 days a week for 5 weeks (from 1 week before until 4 weeks after sinus surgery), and (b) the saline group (n = 10), in which saline substituted PTH at the same dose, mode of administration, and duration. Bone grafting with bovine bone mineral was augmented into 13 sinuses, and bone grafts and implants were simultaneously performed in seven sinuses, in both groups. Animals were sacrificed at 4 weeks after surgery. To determine whether PTH was an effective treatment for osteoporosis, we measured the bone mineral density (BMD) of the right femur using micro-computed tomography and performed radiographic and histometric analyses of the maxillary sinus surgery site. The Mann-Whitney test was used for statistical analysis. RESULTS: It was found that BMD increased in the femur, whereas none of the radiographic and histometric parameters differed significantly between the groups in the sinus, while there were large interindividual variations within groups. CONCLUSIONS: These findings suggest that intermittent PTH does not promote new bone formation in the augmented maxillary sinus of ovariectomized rabbits.

Bone Regeneration Effect of Hyperbaric Oxygen Therapy Duration on Calvarial Defects in Irradiated Rats.

OBJECTIVE: In this study, we evaluated changes in bone remodeling in an irradiated rat calvarial defect model according to duration of hyperbaric oxygen therapy. MATERIALS AND METHODS: The 28 rats were divided into four groups. Radiation of 12 Gy was applied to the skull, and 5-mm critical size defects were formed on both sides of the skull. Bone grafts were applied to one side of formed defects. From the day after surgery, HBO was applied for 0, 1, and 3 weeks. At 6 weeks after bone graft, experimental sites were removed and analyzed for radiography, histology, and histomorphometry. RESULTS: Micro-CT analysis showed a significant increase in new bone volume in the HBO-3 group, with or without bone graft. When bone grafting was performed, BV, BS, and BS/TV all significantly increased. Histomorphometric analysis showed significant increases in %NBA and %BVN in the HBO-1 and HBO-3 groups, regardless of bone graft. CONCLUSION: Hyperbaric oxygen therapy was effective for bone regeneration with only 1 week of treatment.

Synergistic effect of hyperbaric oxygen therapy with PTH [1-34] on calvarial bone graft in irradiated rat.

OBJECTIVE: To determine the synergistic effect of parathyroid hormone (PTH) [1-34] in combination with hyperbaric oxygen (HBO) on bone graft in a rat calvarial bone defect model under impaired osteogenic conditions. MATERIALS AND METHODS: Twenty-four rats were divided into three groups. Localized radiation with a single 12 Gy dose was administered to the calvaria. Four weeks after radiation, calvarial circular defects were created in the parietal bones. All defects were filled with biphasic calcium phosphate. After the bone graft, PTH [1-34] was injected subcutaneously, and HBO was administered. At 6 weeks after the bone graft, the rats were sacrificed, and specimens were harvested. RESULTS: Histomorphometric evaluation showed that the percentage of new bone area was higher in the PTH and PTH/HBO groups than in the control group. The percent residual material area was decreased in the PTH/HBO group compared with the control group. The percentage blood vessel number was highest in the PTH group. Micro-CT evaluation showed that the new bone volume was highest in the PTH/HBO group. The residual material volume was lowest in the PTH/HBO group. CONCLUSION: Within the limitations of this study, our data indicate that PTH combined with HBO may reverse radiation-induced impairment of bone healing.

Bleeding related to dental treatment in patients taking novel oral anticoagulants (NOACs): a retrospective study.

OBJECTIVE: Several novel oral anticoagulants (NOACs) are currently prescribed for patients suffering from atrial fibrillation, pulmonary thromboembolism, and venous thrombosis. However, there is no clinical guideline for dental treatment in patients taking NOACs. This study investigated bleeding events related to various dental treatments. MATERIALS AND METHODS: This retrospective study included 120 patients (153 cases) who were prescribed NOACs and received dental procedures in the Department of Advanced General Dentistry at Yonsei University Dental Hospital from January 2014 to June 2017. The indication for NOACs, initiation of NOACs, duration of discontinuance, creatinine clearance, and type of dental treatment were investigated. Bleeding events were assessed at a follow-up visit to the clinic. RESULTS: Postoperative bleeding occurred in only 9 of the 153 included cases; they comprised 2 cases of scaling, 3 cases of simple extraction, 3 cases of the first stage of implant surgery, and 1 case of resin filling. The creatinine clearance (P = .111) and duration of discontinuance (P = .222) did not differ significantly between the groups with and without bleeding events. CONCLUSIONS: Our data indicate that most dental treatments may be performed in patients taking NOACs without an increased likelihood of bleeding events regardless of the discontinuance duration. Moreover, any postoperative bleeding can be stopped by applying compressive pressure or local hemostatic agents. CLINICAL RELEVANCE: Our study suggests that patients taking NOACs who need dental treatments may have a bleeding tendency based on our retrospective data. Preoperative history taking and treatment modification should therefore be considered before performing dental surgery.

Foreign body removal assisted by an intraoral ultrasound probe.

Ultrasonography has recently been applied to the field of oral and maxillofacial surgery because of its noninvasiveness and ease of use. However, traditional transducers are not used in the intraoral area because of their large size. A novel intraoral transducer was introduced with size, volume, and axis modifications. This new transducer allows the surgeon to approach the intraoral region during dental procedures. This report describes a case of successful removal of a foreign body using the newly developed intraoral ultrasound probe. Precise localization and minimally invasive removal of the foreign body using the intraoral transducer were simultaneously conducted. Because of its many advantages, this intraoral ultrasound transducer has the potential to be applied in oral and maxillofacial surgery.

Oral Papillomatosis in Immunocompromised Patients: A Case Series of Kidney Transplant Recipients and Myelodysplastic Syndrome.

Solitary papilloma is a human papillomavirus (HPV)-induced benign indolent epithelial tumor with limited growth, whereas papillomatosis is an entirely different entity. Papillomatosis requires attention because of its aggressive and recurrent clinical progress with risks of dysplastic and malignant transformation. Recurrent respiratory papillomatosis (RRP) has a high prevalence of dysplasia and reports of transformation to carcinoma-ex-papillomatosis, especially when associated with low-risk HPV type 11. Although papillomatosis seldom occurs in the oral cavity, this report describes 3 cases of oral papillomatosis in immunocompromised patients, with 1 case identified as having HPV type 11. Two cases were kidney transplant recipients and the other case had a history of myelodysplastic syndrome followed by allogeneic bone marrow transplantation and graft-versus-host disease. Oral papillomatosis might be problematic, as in RRP, and periodic oral examination for persistent recurrences and malignant transformation can be beneficial to immunocompromised patients.

Distribution of medical status and medications in elderly patients treated with dental implant surgery covered by national healthcare insurance in Korea.

BACKGROUND: The purpose of this study was to investigate the distribution of systemic diseases and medications in patients older than 65 years of age who visited the hospital for implant treatment, as well as to investigate basic information about surgical complications that may occur after insured implant treatment. METHODS: A total of 126 patients over 65 years of age were treated for implant surgery from October 1, 2013 to October 30, 2016. Electronic chart review was conducted to obtain medical records, which included sex, age, systemic diseases, medication(s) being taken, and control of the medications. Five patients were excluded due to lack of medical records giving information about systemic disease. RESULTS: Of the 126 patients, 112 (88.9%) were taking medication due to systemic disease and 9 patients (7.1%) were not. The sex distribution was 71 women and 55 men and the highest proportion of patients were between 65 and 69 years old. The most common diseases were, from most to least frequent, hypertension, cardiovascular disease, diabetes, and osteoporosis. The drug groups that can cause major complications after dental treatment were classified as hemorrhagic, osteoporotic, and immunosuppressive agents, and were taken by 45 (35.7%), 22 (17.5%) and 4 (3.2%) patients, respectively. CONCLUSION: Given that 88.9% of the elderly patients who were eligible for insurance implant treatment had systemic disease, it is necessary to carefully evaluate patients' medical histories and their general conditions in order to prevent emergencies during implant surgery.

Delayed bleeding after implant surgery in patients taking novel oral anticoagulants: a case report.

The use of novel oral anticoagulants (NOACs) has increased in recent times in an effort to overcome the shortcomings of warfarin. They are being used primarily for the prevention of thrombosis caused by atrial fibrillation and offer the advantages of having fewer drug interactions than warfarin, no dietary restrictions, and no requirement for regular blood tests. Although there is reportedly less postoperative bleeding even if the drug is not discontinued during procedures that can cause local bleeding, such as dental procedures, no well-designed clinical studies have assessed postoperative bleeding associated with the use of these drugs. This article reports a case of a 74-year-old male patient who was taking rivaroxaban. The patient underwent a dental implant procedure after discontinuing rivaroxaban for one day and subsequently suffered delayed bleeding on postoperative day 6. Accordingly, this article also reports that the use of NOACs may also lead to delayed bleeding.

Neural Progenitor-Like Cells Induced from Human Gingiva-Derived Mesenchymal Stem Cells Regulate Myelination of Schwann Cells in Rat Sciatic Nerve Regeneration.

Regeneration of peripheral nerve injury remains a major clinical challenge. Recently, mesenchymal stem cells (MSCs) have been considered as potential candidates for peripheral nerve regeneration; however, the underlying mechanisms remain elusive. Here, we show that human gingiva-derived MSCs (GMSCs) could be directly induced into multipotent NPCs (iNPCs) under minimally manipulated conditions without the introduction of exogenous genes. Using a crush-injury model of rat sciatic nerve, we demonstrate that GMSCs transplanted to the injury site could differentiate into neuronal cells, whereas iNPCs could differentiate into both neuronal and Schwann cells. After crush injury, iNPCs, compared with GMSCs, displayed superior therapeutic effects on axonal regeneration at both the injury site and the distal segment of the injured sciatic nerve. Mechanistically, transplantation of GMSCs, especially iNPCs, significantly attenuated injury-triggered increase in the expression of c-Jun, a transcription factor that functions as a major negative regulator of myelination and plays a central role in dedifferentiation/reprogramming of Schwann cells into a progenitor-like state. Meanwhile, our results also demonstrate that transplantation of GMSCs and iNPCs consistently increased the expression of Krox-20/EGR2, a transcription factor that governs the expression of myelin proteins and facilitates myelination. Altogether, our findings suggest that transplantation of GMSCs and iNPCs promotes peripheral nerve repair/regeneration, possibly by promoting remyelination of Schwann cells mediated via the regulation of the antagonistic myelination regulators, c-Jun and Krox-20/EGR2. Stem Cells Translational Medicine 2017;6:458-470.