Antibiotics alone are often ineffective in the treatment of bacterial biofilm infections and new strategies are needed. Once bacteria shift from their free-swimming state to the structured community of a biofilm, they become much harder to kill with conventional antibiotic regimens. A review by Zhi-Jun Song and colleagues at Denmark’s University Hospital of Copenhagen explores the challenges of diagnosing and eliminating biofilms that form on the surface of implanted medical devices. At present, the best solution is early detection followed by aggressive treatment with multiple antibiotics and removal of the device in question. However, recent research suggests other possible solutions, including drugs that interfere with communication between bacteria or disrupt their ability to anchor to surfaces, and viruses that specifically infect and kill biofilm-forming microbes.

Regenerating periodontal bone defect surrounding periodontal tissue is crucial for orthodontic or dental implant treatment. The declined osteogenic ability of periodontal ligament stem cells (PDLSCs) induced by inflammation stimulus contributes to reduced capacity to regenerate periodontal bone, which brings about a huge challenge for treating periodontitis. Here, inspired by the adhesive property of mussels, we have created adhesive and mineralized hydrogel microspheres loaded with traditional compound cordycepin (MMS-CY). MMS-CY could adhere to the surface of alveolar bone, then promote the migration capacity of PDLSCs and thus recruit them to inflammatory periodontal tissues. Furthermore, MMS-CY rescued the impaired osteogenesis and ligament-forming capacity of PDLSCs, which were suppressed by the inflammation stimulus. Moreover, MMS-CY also displayed the excellent inhibitory effect on the osteoclastic activity. Mechanistically, MMS-CY inhibited the premature senescence induced by the inflammation stimulus through the nuclear factor erythroid 2-related factor (NRF2) pathway and reducing the DNA injury. Utilizing in vivo rat periodontitis model, MMS-CY was demonstrated to enhance the periodontal bone regeneration by improving osteogenesis and inhibiting the osteoclastic activity. Altogether, our study indicated that the multi-pronged approach is promising to promote the periodontal bone regeneration in periodontitis condition by reducing the inflammation-induced stem cell senescence and maintaining bone homeostasis.

Oral submucous fibrosis (OSF), characterized by excessive deposition of extracellular matrix (ECM) that causes oral mucosal tissue sclerosis, and even cancer transformation, is a chronic, progressive fibrosis disease. However, despite some advancements in recent years, no targeted antifibrotic strategies for OSF have been approved; likely because the complicated mechanisms that initiate and drive fibrosis remain to be determined. In this review, we briefly introduce the epidemiology and etiology of OSF. Then, we highlight how cell-intrinsic changes in significant structural cells can drive fibrotic response by regulating biological behaviors, secretion function, and activation of ECM-producing myofibroblasts. In addition, we also discuss the role of innate and adaptive immune cells and how they contribute to the pathogenesis of OSF. Finally, we summarize strategies to interrupt key mechanisms that cause OSF, including modulation of the ECM, inhibition of inflammation, improvement of vascular disturbance. This review will provide potential routes for developing novel anti-OSF therapeutics.

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient’s general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.

The presence of a positive deep surgical margin in tongue squamous cell carcinoma (TSCC) significantly elevates the risk of local recurrence. Therefore, a prompt and precise intraoperative assessment of margin status is imperative to ensure thorough tumor resection. In this study, we integrate Raman imaging technology with an artificial intelligence (AI) generative model, proposing an innovative approach for intraoperative margin status diagnosis. This method utilizes Raman imaging to swiftly and non-invasively capture tissue Raman images, which are then transformed into hematoxylin-eosin (H&E)-stained histopathological images using an AI generative model for histopathological diagnosis. The generated H&E-stained images clearly illustrate the tissue’s pathological conditions. Independently reviewed by three pathologists, the overall diagnostic accuracy for distinguishing between tumor tissue and normal muscle tissue reaches 86.7%. Notably, it outperforms current clinical practices, especially in TSCC with positive lymph node metastasis or moderately differentiated grades. This advancement highlights the potential of AI-enhanced Raman imaging to significantly improve intraoperative assessments and surgical margin evaluations, promising a versatile diagnostic tool beyond TSCC.

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.

The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) “difficult-to-treat”. Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix’s crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.

Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.

Daily chewing has no effect on the fracture toughness of quartz-fiber tooth restoration materials, according to recent research from China. Chun-Yuan Zhang from Sun Yat-Sen University and colleagues investigated how extracted molars — that had been repaired with aligned quartz-fiber ‘posts’ in an epoxy matrix — behave under two kinds of destructive force. They found that molars subjected to five years’ worth of chewing motions through cyclic force loading had identical fracture points and patterns as molars under a static, steadily increasing force. Zhang and colleagues attribute the resilience of the quartz posts to biomechanical movements that allow homogenous transfer of stress into tooth dentin. Chemically enhanced bonding of the quartz posts to teeth and structural reinforcements also contributed to the sturdiness of this novel system.

Acid etching of tooth root surfaces could improve the adhesion of surgical filling materials, according to research from Saudi Arabia and the United States. Khalid Al-Hezaimi at King Saud University and colleagues studied the adhesion of mineral trioxide aggregate (MTA), which is used to fill the ends of tooth roots after infected tissue has been removed. MTA comes in both white and gray colors. The researchers applied MTA to root cavities in 64 extracted human teeth, half of which had been pre-treated by etching with phosphoric acid. They then used microcomputed tomography and scanning electron microscopy to measure the sizes of gaps between the MTA and the root. This showed that the acid pre-etching helped to improve the adhesion of gray MTA, but not white—a finding the researchers attribute to chemical and structural differences between the two colors.

A strategy for suppressing enzymes involved in inflammation could improve patient response to endodontic repair of damaged pulp tissue, report dental researchers in Korea. Direct pulp capping can preserve the health of an infected tooth, although tissue inflammation can undermine the efficacy of this intervention. Proteins known as matrix metalloproteinases (MMPs) contribute to inflammation in numerous different cell types including dental pulp. Sun-Young Kim and colleagues at Kyung Hee University identified a molecule that may limit MMPs’ effects. They found that all-trans retinoic acid (ATRA), a derivative of vitamin A, can reduce production of MMP-2 at non-toxic doses in cultured human dental pulp cells. Although ATRA did not inhibit production of MMP-9, another enzyme involved in pulp cell inflammation, follow-up experiments using inflamed as well as healthy pulp cells should help clarify ATRA’s anti-inflammatory effects.

A combination of vitamin D₃ and the hormone calcitonin may restore normal growth of the lower jaw bone in young patients with diabetes. Diabetes impairs the growth of bones, including those of the head and face, potentially causing dental problems in young patients. Vitamin D₃, which is produced by human skin exposed to sunlight, is known to improve survival of cells that build new bone; calcitonin is known to decrease the activity of cells that resorb bone. Mona Abbassy at King Abdulaziz University in Jeddah, Saudi Arabia, hypothesized that combining the two treatments could have synergistic effects and studied the effects in young rats, using molars as indicators of bone growth. Intermittent injections of vitamin D₃ and calcitonin restored normal bone growth, and show promise for treatment of young patients with diabetes.

A therapeutic technique based on electromagnetic pulses may provide relief from pain caused by grinding teeth during sleep. Sleep bruxism is a condition in which sufferers grind their teeth continuously at night, causing significant discomfort and jaw pain. In a pilot study, Jing-Lu Zhang at Nanjing Medical University, China, and co-workers investigated the effects of a non-invasive technique called repetitive transcranial magnetic stimulation (rTMS) on sleep bruxism in 12 patients. The team used electromagnetic coils to send 20 min of targeted magnetic pulses to the primary motor cortex of each patient every day for 5 days. The patients rated their levels of pain before, during and after rTMS treatment, and reported a significant drop in soreness levels. Further trials will verify if rTMS therapy is beneficial for those suffering from sleep bruxism.

The antibacterial activity of dental composites with ammonium polymer additives depends on the polymers' chain length. Dental composites formed from calcium phosphate in its nanoparticulate form are used as a remineralization agent for tooth lesions and to prevent tooth decay. To further prevent decay, which occurs following bacterial biofilm formation, antibacterial agents can be added to the composites. Hockin HK Xu, University of Maryland, USA, Yu-Xing Bai at Capital Medical University in Beijing, and colleagues synthesized quaternary ammonium methacrylates with chain lengths varying from 3 to 18 carbons, and assessed their anti-biofilm activity in calcium phosphate composites. The antibacterial efficacy increased with chain length until a maximum was reached at 16, the efficacy decreasing thereafter. The maximum efficacy resulted in a 10-fold reduction in biofilm metabolic activity and acid production, without any detrimental mechanical effects.

Diseases of the mouth lining, or oral mucosa, occur with a loss of nerve endings crucial for sensing touch, research from Germany suggests. The perception of touch in the oral mucosa involves Merkel cells, which join to Aβ-nerve fibres to send impulses to the central nervous system. Yüksel Korkmaz and co-workers at the University of Cologne examined the distribution of Merkel cells and Aβ fibres in healthy tissues and in tissues with the diseases lichen planus and hyperkeratosis. They found that the diseased tissues contained far fewer Aβ-nerve endings, and these were rarely joined to Merkel cells, implying that both diseases impair the sense of touch in the mouth. Based on their findings, the researchers suggest that a healthy mucosa is essential before applying dental prostheses. This will facilitate a harmonic occlusion and protect the oral mucosa against harmful unphysiological occlusal forces, which may occur after impaired sensation in the mouth.

Expression of a regulator of tooth mineralization starts late during embryonic development in mice, continuing until four weeks after birth. Jian-Jun Hao and his colleagues at the University of Connecticut Health Center in the USA created a mouse model for tracking when and where the protein Fam20C is expressed in the body. The researchers engineered mice to make green fluorescence protein, a visible marker, in any tissues where Fam20C would normally be found. They saw the green glow in the dentin-forming cells of the teeth and in bone-forming cells of the craniofacial and alveolar bones starting at day 17.5 of embryonic development. The green signal decreased after the mice reached four weeks of age. The findings — and the mouse model itself — could lead to therapies for dentin and bone defects.

The success of replanting vertically fractured teeth depends on crown restoration and healthy periodontal tissues. Using 40 upper first premolar teeth that had been extracted from adolescents for orthodontic reasons, a team led by Wen-Mei Wang from Nanjing University Medical School, China, split each tooth in two, creating vertical fractures. The researchers rejoined the halves with a bonding resin and applied metal crowns to half the teeth. To simulate the two kinds of replantation that can occur, they either attached a layer of silicone rubber to mimic periodontal ligaments or attached epoxy resin as a stand-in for bone. The researchers then applied cyclic forces to reproduce the repeated stress of chewing and found that crown restoration and repaired periodontal fibers are both important for the long-term health of vertically fractured teeth.

The strength of dental resin-based adhesives could be improved by adding light-activated riboflavin (RF, also known as vitamin B₂). Amr Fawzy and his team at the National University of Singapore, analysed the resin–dentin interface of human molars in which dentin was restored with adhesives containing different concentrations of RF. Following storage of the restored teeth for up to nine months in artificial saliva, they found that the strongest bonds formed with adhesives containing 3% RF. Scanning electron microscopy showed that this was due to RF’s crosslinking effect on dentin collagen fibrils. This is consistent with their previous findings that dentin pre-treatment with RF strengthens the collagen network. Adding 3% light-activated RF to dentin adhesives could make dental composite restorations more long-lasting without increasing the number of clinical steps required.

Zirconia-based ceramic crowns are strong, mechanically reliable and resist loading fatigue over time, according to research from China. Crowns made entirely from ceramics are frequently used as tooth replacements, but repeated stresses can cause cracks to propagate and sometimes lead to total failure of the crown. Dong-Sheng Zhang at Shanghai University and co-workers compared the impact of cyclic loading on two leading types of ceramic crown: one is made from hot-press lithium disilicate and the other from zirconia core materials. The researchers subjected the crowns to two million loading cycles of different magnitudes and measured the changes in the crowns' elasticity, hardness and fracture toughness over time. They found that cyclic loading had no significant influence on zirconia crowns, but the lithium-based crowns had a markedly lower load-bearing capacity.

The use of stem cells to accelerate bone regeneration has been monitored in real time in rats using three-dimensional imaging. The work was carried out by Khalid Al-Hezaimi and colleagues at King Saud University, Saudi Arabia, in collaboration with No-Hee Park of the University of California. Mesenchymal stem cells were harvested from rat hind leg bones. The researchers then drilled holes in rat skulls and filled them with stem cells covered with collagen membrane with and without tricalcium phosphate granules, or collagen membrane alone. Micro-computed tomography revealed that differentiation of stem cells into mature bone cells took approximately 2 weeks. Bone regeneration over a 10-week period was significantly faster with the stem cell treatments. Adding tricalcium phosphate weakened the regenerated bone, despite previous work suggesting it might promote bone cell formation

An investigation into the interaction between tooth root cells and an inflammatory protein sheds light on root degradation following injury. Osteoclast cells digest old bone to release nutrients and recycle bone tissues in a vital process called bone resorption. Cementum, the mineral substance covering tooth roots, is not usually resorbed, but injury to the tissues surrounding roots often triggers inflammation followed by root degradation. To understand this phenomenon better, Ruchanee Salingcarnboriboon Ampornaramveth at Chulalongkorn University in Bangkok, Thailand, and co-workers investigated whether cementum cells can promote the formation of osteoclasts. They found that when cementum cells were treated with interleukin 1 beta, an inflammatory protein expressed at high levels in tissues following injury, levels of another protein needed for osteoclast formation increased. This boosted osteoclast formation around roots, resulting in root resorption

Collagen gel containing basic fibroblast growth factor could assist the regeneration of submandibular glands after damage during surgery. The slow healing of these large salivary glands, which lie beneath the floor of the mouth, causes difficulties with speaking, swallowing and digestion, and an increased susceptibility to oral infection. These problems can significantly impair a patient's quality of life. Fumitaka Kobayashi at Tokyo Dental College and co-workers explored the healing potential of basic fibroblast growth factor in collagen gel using rats that had been wounded to model surgical damage. They also monitored the proliferation and development of the specific types of cell involved in repairing the wounded tissue. Treating the wounds using collagen containing growth factor accelerated and improved healing to a greater extent than using collagen gel alone.

The fibrous epulis, a common tumor-like lesion of the gingiva, appears in the interdental papilla as a result of local irritation. Lesions are asymptomatic and have a variable growth rate. A 75-year-old woman was referred for the evaluation of a large painless gingival mass. It had started 10 years back and has been increasing in size the last year. No bone involvement was noted. The tumor was totally removed by excision with surgical scalpel under local anesthesia without teeth extraction. The microscopic findings were suggestive of a fibrous epulis. Differential diagnosis, clinical considerations and factors to prevent recurrence are discussed.

The timing and site of action of two key enzymes help regulate the formation of cementum, one of the mineralized substances of teeth. An international team led by Brian Foster from the US National Institute of Arthritis and Musculoskeletal and Skin Diseases considered the roles of two enzymes — tissue non-specific phosphatase (TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) — in cementum development. They showed in mice that early TNAP expression created a particular environment in teeth with low levels of pyrophosphate, a mineral inhibitor. This promoted the creation of a type of cementum that does not incorporate cells into its structure. Later on in development, the expression of NPP1 boosted levels of pyrophosphate, which restricted this type of cementum. These enzymes had little effect on cementum containing cells. The researchers confirmed these patterns in extracted human teeth.

Cleaning root canals with chlorhexidine antiseptic leaves a sustained residual antimicrobial effect, research from Spain shows. Root canal surgery carries a high risk of infection: the bacteria Enterococcus faecalis is commonly found following the procedure. Effective irrigation of root canals during root canal treatment disinfects the area and can provide a barrier to future infection by leaving an antimicrobial residue to attack remaining bacteria. To verify the most effective treatment, Carmen Maria Ferrer-Luque and colleagues at the University of Granada compared three irrigation solutions on root canals infected with E. faecalis. After 50 days, the team found significant bacterial growth on 69% of roots treated with weak solutions (0.2%) of cetrimide and chlorhexidine. A more potent chlorhexidine solution (2%), however, indicated a longer-lasting residual effect, with E. faecalis growth on less than 35% of roots.

Children undergoing treatment for leukaemia may benefit from a drug that prevents mucositis, or injury to the cells that line the mouth. A team led by Dorina Lauritano from the University of Milan Bicocca, Italy, tested a drug called palifermin in 20 patients under 16 years of age who received high doses of chemotherapy and radiation, followed by stem cell transplantations to treat acute lymphoblastic leukaemia. Palifermin is a modified version of a naturally occurring human protein called keratinocyte growth factor. It is marketed as Kepivance for the prevention of oral mucositis for all age groups. However, information on the safety and efficacy of the drug in paediatric populations was limited. Lauritano and her colleagues found that Palifermin significantly reduced the severity of mucositis compared to a control group that did not receive the drug.

Better education and awareness campaigns are needed to encourage people who notice symptoms of oral cancer to quickly have their lesions inspected by medical or dental professionals. Led by Giuseppe Colella and Giuseppina Campisi, a research team from the Universities of Palermo and Naples in Italy interviewed 156 people with squamous cell carcinoma of the oral cavity to determine the time taken between patients first noticing signs of cancer and then consulting physicians or dentists. People with knowledge or personal experience with cancer tended to seek medical assistance much earlier than people who were in denial or were unaware of the problem, the researchers found. Older patients showed a shorter delay than younger patients. The team calls for educational interventions to encourage early diagnosis and treatment of oral cancer, a disease responsible for an estimated 130 000 deaths worldwide each year.

Sandblasting of glass fiber posts could enhance resin cement adhesion during tooth restoration, as scientists in China suggest. During endodontic treatment, such as root canal surgery, teeth must be hollowed out and rebuilt. Glass fiber posts and resin cements can replace lost structural support, but weak bonding between them can lead to restoration failure. In a study using human teeth, Chang Liu and co-workers at Jilin University in China analyzed the bonding of four different resin cements under different conditions. The type of resin cement significantly affected bonding to the posts regardless of pre-treatment, with two cements outperforming the others. However, one type of cement, called DMG Luxacore, adhered far better to the post following small-scale sandblasting. The sandblasting roughens the glass surface, increasing both the bonding area and interlocking between post and cement.

Gene expression profiling reveals how surrounding tissues may the promote growth of a benign but aggressive class of oral tumor. The process by which keratocystic odontogenic tumors (KCOT) develop is poorly understood, but evidence suggests that KCOT cells receive important cues from the stromal cells that surround the tumor. Researchers led by Tie-Jun Li and Feng Chen of China’s Peking University School and Hospital of Stomatology analyzed and compared the gene activity in KCOT stromal tissue with healthy samples. They identified a secreted protein, LOXL4, which is produced at considerably elevated levels in KCOT samples. Preliminary functional analysis suggests that LOXL4 can stimulate blood vessel growth, and may also promote proliferation and invasive growth in endothelial cells. These findings thus illustrate one possible mechanism by which cells in the tumor environment could stimulate KCOT formation and expansion.

A comprehensive survey of six orthodontic treatment centers in China indicates a high level of consistency with which Chinese orthodontic specialists assess treatment outcomes. The study, led by Tian-Min Xu of Peking University, is the first of its kind to compare the values of different combinations of methods for such assessments. The three most commonly used approaches to evaluate the success of orthodontic procedures are: study, or plaster, casts; cephalometric films, or head images (traditionally x-rays); and facial photographs. Previous studies examined the predictive potential of each of these methods in isolation. Xu and colleagues showed that study casts were the most reliable predictors of successful treatment. The additional use of cephalometric films and facial photographs increased the likelihood of a reliable assessment. More than 300, 000 Chinese patients undergo orthodontic procedures annually.