Effect of acid etching on marginal adaptation of mineral trioxide aggregate to apical dentin:microcomputed tomography and scanning electron microscopy analysis

The present investigation assessed the effect of acid etching on marginal adaptation of white- and gray-colored mineral trioxide aggregate （MTA） to apical dentin using microcomputed tomography （micro-CT） and scanning electron microscopy （SEM）. Sixty-four extracted single-rooted human maxillary teeth were used. Following root-end resection and apical preparation, the teeth were equally divided into four groups according to the following root end filling materials： （i） white-colored MTA （WMTA）, （ii） etched WMTA （EWMTA）, （iii） gray-colored MTA （GMTA） and （iv） etched GMTA （EGMTA）. After 48 h, the interface between root-end filling materials and the dentinal walls was assessed using micro-CT and SEM. Data were statistically analyzed using the KruskaI-Wallis and Dunn tests. Micro-CT analysis revealed gap volumes between the apical cavity dentin walls and EGMTA, GMTA, EWMTA and WMTA of （0.007 1±0.004） mm3, （0.053±0.002） mm3, （0.003 6±0.001） mm3 and （0.005 9±0.002） mm3 respectively. SEM analysis revealed gap sizes for EGMTA, WMTA, EWMTA and GMTA to be （492.3±13.8） μm, （594.5±17.12）μm, （543.1±15.33） μm and （910.7±26.2）μm respectively. A significant difference in gap size between root end preparations filled with GMTA and EGMTA was found （P〈O.05）. No significance difference in gap size between WMTA and EWMTA were found in either SEM or micro-CT analysis. In conclusion, pre-etching of apical dentin can provide a better seal for GMTA but not for WMTA.

Formation of Dental Plaque Biofilm on Different Titanium Surfaces and Evaluate Antimicrobial Effects of Mouthrinses on Dental Plaque Biofilm

The aim of this study was to evaluate the effect of the morphology of titanium implant surfaces on dental plaque biofilm formation and the antimicrobial effects of mouthrinses on dental plaque biofilms regarding these titanium surfaces by using an open biofilm model. The average surface roughness(RA) of three types of titanium surfaces(Smooth, hydroxyapatite(HA), sandblast large grit and acid-etching(SLA)) were tested by atomic force microscope(AFM). Subgingival plaques were collected and cultured on titanium surfaces for 4 hours to 2 weeks. After treatment with mouthrinses, characterization of dental plaque biofilms was tested by field-emission SEM(FESEM) and confocal laser scanning microscopy(CLSM). The results of AFM and SEM showed that the surface roughness and biofilm thickness of HA and SLA surfaces were significantly higher than those of smooth surface. In addition, it was revealed that the mouthrinses were effective on the killing of young dental plaque biofilms, while the more mature biofilm(14-day-old) exhibited a stronger resistance to mouthrinses used in this study. In conclusion, the roughness of titanium surfaces can affect the dental plaque biofilm formation and Colgate Plax and Listerine COOL MINT are effective mouthrinses to kill dental plaques at the early stage of biofilm growth on the titanium implant surfaces.

Laser capture microdissection enables cellular and molecular studies of tooth root development

Epithelial-mesenchymal interactions（EMIs） are critical for tooth development.Molecular mechanisms mediating these interactions in root formation is not well understood.Laser capture microdissection（LCM） and subsequent microarray analyses enable large scale in situ molecular and cellular studies of root formation but to date have been hindered by technical challenges of gaining intact histological sections of non-decalcified mineralized teeth or jaws with well-preserved RNA.Here,we describe a new method to overcome this obstacle that permits LCM of dental epithelia,adjacent mesenchyme,odontoblasts and cementoblasts from mouse incisors and molars during root development.Using this method,we obtained RNA samples of high quality and successfully performed microarray analyses.Robust differences in gene expression,as well as genes not previously associated with root formation,were identified.Comparison of gene expression data from microarray with real-time reverse transcriptase polymerase chain reaction（RT-PCR） supported our findings.These genes include known markers of dental epithelia,mesenchyme,cementoblasts and odontoblasts,as well as novel genes such as those in the fibulin family.In conclusion,our new approach in tissue preparation enables LCM collection of intact cells with well-preserved RNA allowing subsequent gene expression analyses using microarray and RT-PCR to define key regulators of tooth root development.

Differentiation of periapical granulomas and cysts by using dental MRI: a pilot study

The purpose of this pilot study was to evaluate whether periapical granulomas can be differentiated from periapical cysts in vivo by using dental magnetic resonance imaging(MRI). Prior to apicoectomy, 11 patients with radiographically confirmed periapical lesions underwent dental MRI, including fat-saturated T2-weighted(T2 wFS) images, non-contrast-enhanced T1-weighted images with and without fat saturation(T1 w/T1 wFS), and contrast-enhanced fat-saturated T1-weighted(T1 wFS+C) images. Two independent observers performed structured image analysis of MRI datasets twice. A total of 15 diagnostic MRI criteria were evaluated, and histopathological results(6 granulomas and 5 cysts) were compared with MRI characteristics. Statistical analysis was performed using intraclass correlation coefficient(ICC), Cohen’s kappa(κ), Mann–Whitney U-test and Fisher’s exact test. Lesion identification and consecutive structured image analysis was possible on T2 wFS and T1 wFS+C MRI images. A high reproducibility was shown for MRI measurements of the maximum lesion diameter(intraobserver ICC = 0.996/0.998; interobserver ICC = 0.997), for the "peripheral rim" thickness(intraobserver ICC = 0.988/0.984; interobserver ICC = 0.970), and for all non-quantitative MRI criteria(intraobserver-κ = 0.990/0.995; interobserver-κ = 0.988). In accordance with histopathological results, six MRI criteria allowed for a clear differentiation between cysts and granulomas:(1) outer margin of lesion,(2) texture of "peripheral rim" in T1 wFS+C,(3)texture of "lesion center" in T2 wFS,(4) surrounding tissue involvement in T2 wFS,(5) surrounding tissue involvement in T1 wFS+C and(6) maximum "peripheral rim" thickness(all: P < 0.05). In conclusion, this pilot study indicates that radiation-free dental MRI enables a reliable differentiation between periapical cysts and granulomas in vivo. Thus, MRI may substantially improve treatment strategies and help to avoid unnecessary surgery in apical periodontitis.

Biomaterial scaffolds in maxillofacial bone tissue engineering:A review of recent advances

Maxillofacial bone defects caused by congenital malformations,trauma,tumors,and inflammation can severely affect functions and aesthetics of maxillofacial region.Despite certain successful clinical applications of biomaterial scaffolds,ideal bone regeneration remains a challenge in maxillofacial region due to its irregular shape,complex structure,and unique biological functions.Scaffolds that address multiple needs of maxillofacial bone regeneration are under development to optimize bone regeneration capacity,costs,operational convenience.etc.In this review,we first highlight the special considerations of bone regeneration in maxillofacial region and provide an overview of the biomaterial scaffolds for maxillofacial bone regeneration under clinical examination and their efficacy,which provide basis and directions for future scaffold design.Latest advances of these scaffolds are then discussed,as well as future perspectives and challenges.Deepening our understanding of these scaffolds will help foster better innovations to improve the outcome of maxillofacial bone tissue engineering.

Antibiofilm peptides against biofilms on titanium and hydroxyapatite surfaces

Biofilms are the main challenges in the treatment of common oral diseases such as caries,gingival and endodontic infection and periimplantitis.Oral plaque is the origin of microbes colonizing in the form of biofilms on hydroxyapatite(tooth)and titanium(dental implant)surfaces.In this study,hydroxyapatite(HA)and titanium(Ti)disks were introduced,and their surface morphology was both qualitatively and quantitatively analyzed by a scanning electron microscope(SEM)and atomic force microscope(AFM).The average roughness of Ti disks(77.6±18.3 nm)was less than that of HA(146.1±38.5 nm)(p<0.05).Oral multispecies biofilms which were cultured on Ti and HA disks for 6 h and three weeks were visualized by SEM.We investigated the ability of two new antibiofilm peptides,DJK-5 and 1018,to induce killing of bacteria in oral multispecies biofilms on Ti and HA disks.A 6-h treatment by DJK-5 and 1018(2 or 10μg/mL)significantly reduced biomass of the multispecies biofilms on both Ti and HA disks.DJK-5 was able to kill more bacteria(40.4–75.9%)than 1018(30.4–67.0%)on both surfaces(p<0.05).DJK-5 also led to a more effective killing of microbes after a 3-min treatment of 3-day-old and 3-week-old biofilms on Ti and HA surfaces,compared to peptide 1018 and chlorhexidine(p<0.05).No significant difference was found in the amount of biofilm killing between Ti and HA surfaces.Both peptide DJK-5 and 1018 may potentially be used as effective antibiofilm agents in clinical dentistry.

Epigallocatechin-3-gallate/mineralization precursors co-delivery hollow mesoporous nanosystem for synergistic manipulation of dentin exposure

As a global public health focus,oral health plays a vital role in facilitating overall health.Defected teeth characterized by exposure of dentin generally increase the risk of aggravating oral diseases.The exposed dentinal tubules provide channels for irritants and bacterial invasion,leading to dentin hypersensitivity and even pulp inflammation.Cariogenic bacterial adhesion and biofilm formation on dentin are responsible for tooth demineralization and caries.It remains a clinical challenge to achieve the integration of tubule occlusion,collagen mineralization,and antibiofilm functions for managing exposed dentin.To address this issue,an epigallocatechin-3-gallate(EGCG)and poly(allylamine)-stabilized amorphous calcium phosphate(PAH-ACP)co-delivery hollow mesoporous silica(HMS)nanosystem(E/PA@HMS)was herein developed.The application of E/PA@HMS effectively occluded the dentinal tubules with acid-and abrasion-resistant stability and inhibited the biofilm formation of Streptococcus mutans.Intrafibrillar mineralization of collagen fibrils and remineralization of demineralized dentin were induced by E/PA@HMS.The odontogenic differentiation and mineralization of dental pulp cells with high biocompatibility were also promoted.Animal experiments showed that E/PA@HMS durably sealed the tubules and inhibited biofilm growth up to 14 days.Thus,the development of the E/PA@HMS nanosystem provides promising benefits for protecting exposed dentin through the coordinated manipulation of dentin caries and hypersensitivity.

Advances in nanomaterials for the diagnosis and treatment of head and neck cancers:A review

Nanomaterials(NMs)have increasingly been used for the diagnosis and treatment of head and neck cancers(HNCs)over the past decade.HNCs can easily infiltrate surrounding tissues and form distant metastases,meaning that most patients with HNC are diagnosed at an advanced stage and often have a poor prognosis.Since NMs can be used to deliver various agents,including imaging agents,drugs,genes,vaccines,radiosensitisers,and photosensitisers,they play a crucial role in the development of novel technologies for the diagnosis and treatment of HNCs.Indeed,NMs have been reported to enhance delivery efficiency and improve the prognosis of patients with HNC by allowing targeted delivery,controlled release,responses to stimuli,and the delivery of multiple agents.In this review,we consider recent advances in NMs that could be used to improve the diagnosis,treatment,and prognosis of patients with HNC and the potential for future research.

Cell-scaffold interactions in tissue engineering for oral and craniofacial reconstruction

Tissue engineering(TE)is critical in oral and craniofacial reconstruction.One of the most popular topics on the biomaterial-based tissue regeneration process may be the interaction between cells and scaffolds.An increasing number of studies have identified the variables affecting cell-scaffold interaction.The creation and investigation of new scaffolds for TE and regenerative medicine based on specific interactions have become possible owing to these findings.This review discusses the effects of various types of scaffold materials on cells in TE.Because the intrinsic properties of scaffolds are essential,the influence of the physical,chemical,mechanical,and biological characteristics of scaffold materials on cell-scaffold interaction that has been discovered in recent research is elaborated in this review.The components carried by scaffolds,the degradation process,and the role of degraded products in cell-scaffold interactions are examined.Further,the roles of cells,including cell types,functions,and adhesion mechanisms,and extracellular matrix are discussed.Finally,the latest research progress on cell-scaffold interactions among various engineered tissues or organs in the oral and craniofacial region is summarized.A deeper understanding of cell-scaffold interactions is anticipated to benefit the development of TE and regenerative medicine.

Corrigendum to“Epigallocatechin-3-gallate/mineralization precursors co-delivery hollow mesoporous nanosystem for synergistic manipulation of dentin exposure”[Bioact.Mater.23(2023)394-408]

The authors regret the incorrect publication of Fig.5,which was not identified during the proofing stage.During a self-check,we unfortunately found that the insets(250μg/mL,1 day)in Fig.5b/c and the image(1000μg/mL,3 days)in Fig.5c were mistakenly used during figure assembly.We tracked down the original data obtained in June 2022,and have replaced Fig.5 with the correct image as follows.The authors would like to apologise for any inconvenience caused and state that the correction does not change the scientific conclusions of the article in any way.

Promoting oral mucosal wound healing using a DCS-RuB_(2)A_(2) hydrogel based on a photoreactive antibacterial and sustained release of BMSCs

The high occurrence rate and difficulties in symptom control are listed as the major problems of oral mucosal disease by medical professionals.Following the development of oral mucosal lesions,the oral microenvironment changes,immunity declines,and continuous bacterial stimulation causes wound infection.Traditional antibacterial drugs are ineffective for oral mucosal lesions.To overcome this problem,a light-responsive antibacterial hydrogel containing sustained-release BMSCs was inspired by the trauma environment in the oral cavity,which is different from that on the body surface since it mostly remains under dark conditions.In the absence of light,the hydrogel seals the wound to form a barrier,exerts a natural bacteriostatic effect,and prevents invasion by foreign bacteria.Simultaneously,mesenchymal stem cells are presented,and the released growth factors and other substances have excellent anti-inflammatory and angiogenic effects,which result in rapid repair of the damaged site.Under light conditions,after photo-induced shedding of the hydrogel,RuB_(2)A exerts an antibacterial effect accompanied by degradation of the hydrogel.Results in a rat oral mucosal repair model demonstrate that DCS-RuB_(2)A_(2)-BMSCs could rapidly repair the oral mucosa within 4 days.Sequencing data provide ideas for further analysis of the intrinsic molecular mechanisms and signaling pathways.Taken together,our results suggest that this light-responsive antibacterial hydrogel loaded with BMSCs can be used for rapid wound repair and may advance the development of therapeutic strategies for the treatment of clinical oral mucosal defects.

A ROS-responsive hydrogel incorporated with dental follicle stem cell-derived small extracellular vesicles promotes dental pulp repair by ameliorating oxidative stress

Pulpitis,an inflammatory disease of dental pulp tissues,ultimately results in the loss of pulp defense properties.Existing clinical modalities cannot effectively promote inflamed pulp repair.Oxidative stress is a major obstacle inhibiting pulp repair.Due to their powerful antioxidative capacity,mesenchymal stem cell-derived small extracellular vesicles(MSC-sEVs)exhibit potential for treating oxidative stress-related disorders.However,whether MSC-sEVs shield dental pulp tissues from oxidative damage is largely unknown.Here,we showed that dental follicle stem cell-derived sEVs(DFSC-sEVs)have antioxidative and prohealing effects on a rat LPS-induced pulpitis model by enhancing the survival,proliferation and odontogenesis of H_(2)O_(2)-injured dental pulp stem cells(DPSCs).Additionally,DFSC-sEVs restored the oxidative/antioxidative balance in DPSC mitochondria and had comparable effects on ameliorating mitochondrial dysfunction with the mitochondrion-targeted antioxidant Mito-Tempo.To improve the efficacy of DFSC-sEVs,we fabricated an intelligent and injectable hydrogel to release DFSC-sEVs by combining sodium alginate(SA)and the ROS sensor RhB-AC.The newly formed SA-RhB hydrogel efficiently encapsulates DFSC-sEVs and exhibits controlled release of DFSC-sEVs in a HClO/ClO^(-)concentration-dependent manner,providing a synergistic antioxidant effect with DFSC-sEVs.These results suggest that DFSC-sEVs-loaded SA-RhB is a promising minimally invasive treatment for pulpitis by enhancing tissue repair in the pulp wound microenvironment.

Dental plaque-inspired versatile nanosystem for caries prevention and tooth restoration

Dental caries is one of the most prevalent human diseases resulting from tooth demineralization caused by acid production of bacteria plaque.It remains challenges for current practice to specifically identify,intervene and interrupt the development of caries while restoring defects.In this study,inspired by natural dental plaque,a stimuli-responsive multidrug delivery system(PMs@NaF-SAP)has been developed to prevent tooth decay and promote enamel restoration.Classic spherical core-shell structures of micelles dual-loaded with antibacterial and restorative agents are self-assembled into bacteria-responsive multidrug delivery system based on the pH-cleavable boronate ester bond,followed by conjugation with salivary-acquired peptide(SAP)to endow the nanoparticle with strong adhesion to tooth enamel.The constructed PMs@NaF-SAP specifically adheres to tooth,identifies cariogenic conditions and intelligently releases drugs at acidic pH,thereby providing antibacterial adhesion and cariogenic biofilm resistance,and restoring the microarchitecture and mechanical properties of demineralized teeth.Topical treatment with PMs@NaF-SAP effectively diminishes the onset and severity of caries without impacting oral microbiota diversity or surrounding mucosal tissues.These findings demonstrate this novel nanotherapy has potential as a promising biomedical application for caries prevention and tooth defect restoration while resisting biofilm-associated diseases in a controlled manner activated by pathological bacteria.

Biomaterial scaffolds for clinical procedures in endodontic regeneration

Regenerative endodontic procedures have been rapidly evolving over the past two decades and are employed extensively in clinical endodontics.These procedures have been perceived as valuable adjuvants to conventional strategies in the treatment of necrotic immature permanent teeth that were deemed to have poor prognosis.As a component biological triad of tissue engineering(i.e.,stem cells,growth factors and scaffolds),biomaterial scaffolds have demonstrated clinical potential as an armamentarium in regenerative endodontic procedures and achieved remarkable advancements.The aim of the present review is to provide a broad overview of biomaterials employed for scaffolding in regenerative endodontics.The favorable properties and limitations of biomaterials organized in naturally derived,host-derived and synthetic material categories were discussed.Preclinical and clinical studies published over the past five years on the performance of biomaterial scaffolds,as well as current challenges and future perspectives for the application of biomaterials for scaffolding and clinical evaluation of biomaterial scaffolds in regenerative endodontic procedures were addressed in depth.