Peking University Stomatological Hospital

Microbes appear in every corner of human life, and microbes affect every aspect of human life. The human oral cavity contains a number of different habitats. Synergy and interaction of variable oral microorganisms help human body against invasion of undesirable stimulation outside. However, imbalance of microbial flora contributes to oral diseases and systemic diseases. Oral microbiomes play an important role in the human microbial community and human health. The use of recently developed molecular methods has greatly expanded our knowledge of the composition and function of the oral microbiome in health and disease. Studies in oral microbiomes and their interactions with microbiomes in variable body sites and variable health condition are critical in our cognition of our body and how to make effect on human health improvement.

OBJECTIVES: The present study aimed to investigate whether exosomes derived from miR-375-overexpressing human adipose mesenchymal stem cells (hASCs) could enhance bone regeneration. MATERIALS AND METHODS: Exosomes enriched with miR-375 (Exo [miR-375]) were generated from hASCs stably overexpressing miR-375 after lentiviral transfection and identified with transmission electron microscopy, nanosight and western blotting. The construction efficiency of Exo (miR-375) was evaluated with qRT-PCR and incubated with human bone marrow mesenchymal stem cells (hBMSCs) to optimize the effective dosage. Then, the osteogenic capability of Exo (miR-375) was investigated with ALP and ARS assays. Furthermore, dual-luciferase reporter assay and western blotting were conducted to reveal the underlying mechanism of miR-375 in osteogenic regulation. Finally, Exo (miR-375) were embedded with hydrogel and applied to a rat model of calvarial defect, and μ-CT analysis and histological examination were conducted to evaluate the therapeutic effects of Exo (miR-375) in bone regeneration. RESULTS: miR-375 could be enriched in exosomes by overexpressing in the parent cells. Administration of Exo (miR-375) at 50 μg/mL improved the osteogenic differentiation of hBMSCs. With miR-375 absorbed by hBMSCs, insulin-like growth factor binding protein 3 (IGFBP3) was inhibited by binding to its 3'UTR, and recombinant IGFBP3 protein reduced the osteogenic effects triggered by Exo (miR-375). After incorporated with hydrogel, Exo (miR-375) displayed a slow and controlled release, and further in vivo analysis demonstrated that Exo (miR-375) enhanced the bone regenerative capacity in a rat model of calvarial defect. CONCLUSIONS: Taken together, our study demonstrated that exosomes derived from miR-375-overexpressing hASCs promoted bone regeneration.

OBJECTIVES: In order to provide a more comprehensive understanding of the effects of SARS-CoV-2 on oral health and possible saliva transmission, we performed RNA-seq profiles analysis from public databases and also a questionnaire survey on oral-related symptoms of COVID-19 patients. MATERIALS AND METHODS: To analyse ACE2 expression in salivary glands, bulk RNA-seq profiles from four public datasets including 31 COVID-19 patients were recruited. Saliva and oropharyngeal swabs were collected. SARS-CoV-2 nucleic acids in saliva were detected by real-time polymerase chain reaction (RT-PCR). Additionally, a questionnaire survey on various oral symptoms such as dry mouth and amblygeustia was also carried out on COVID-19 patients. RESULTS: ACE2 expression was present at detectable levels in the salivary glands. In addition, of four cases with positive detection of salivary SARS-CoV-2 nucleic acids, three (75%) were critically ill on ventilator support. Furthermore, we observed the two major oral-related symptoms, dry mouth (46.3%) and amblygeustia (47.2%), were manifested by a relatively high proportion of 108 COVID-19 patients who accepted the questionnaire survey. CONCLUSIONS: This study confirms the expression of ACE2 in the salivary glands and demonstrates the possibility of SARS-CoV-2 infection of salivary glands. Saliva may be a new source of diagnostic specimens for critically ill patients, since it can be easily collected without any invasive procedures. In addition, dry mouth and amblygeustia can be considered as initial symptoms of COVID-19 infection.

MicroRNA miR-26a and long noncoding RNA (lncRNA) MEG3 gene have been independently reported to be tumor suppressor genes in various cancers, but neither has been previously associated with tongue squamous cell carcinoma (TSCC). We report here that miR-26a and lncRNA MEG3 gene expression were both strongly reduced in TSCC compared with levels in matched nonmalignant tissues, and combined low expression levels of both miR-26a and MEG3 emerged as an independent prognostic factor for poor clinical outcome in TSCC patients. Assays in the human TSCC cell lines SCC-15 and CAL27 showed that miR-26a targets the DNA methyltransferase 3B transcript and that its inhibition may result in the upregulation of MEG3, providing a plausible link between the observed reduction of miR-26a and MEG3 in TSCC tissue. Furthermore, the overexpression of miR-26a or MEG3 in SCC-15 and CAL27 cells inhibited cell proliferation and cell cycle progression, and promoted cell apoptosis. Considering the poor prognostic outcomes associated with reduced miR-26a and MEG3, our findings imply that these factors likely play important antitumor effects in TSCC pathogenesis. Furthermore, they represent potential prognostic biomarkers for stratification of TSCC patients.

Nanozymes, as one of the most efficient reactive oxygen species (ROS)-scavenging biomaterials, are receiving wide attention in promoting diabetic wound healing. Despite recent attempts at improving the catalytic efficiency of Pt-based nanozymes (e.g., PtCu, one of the best systems), they still display quite limited ROS scavenging capacity and ROS-dependent antibacterial effects on bacteria or immunocytes, which leads to uncontrolled and poor diabetic wound healing. Hence, a new class of multifunctional PtCuTe nanosheets with excellent catalytic, ROS-independent antibacterial, proangiogenic, anti-inflammatory, and immuno-modulatory properties for boosting the diabetic wound healing, is reported. The PtCuTe nanosheets show stronger ROS scavenging capacity and better antibacterial effects than PtCu. It is also revealed that the PtCuTe can enhance vascular tube formation, stimulate macrophage polarization toward the M2 phenotype and improve fibroblast mobility, outperforming conventional PtCu. Moreover, PtCuTe promotes crosstalk between different cell types to form a positive feedback loop. Consequently, PtCuTe stimulates a proregenerative environment with relevant cell populations to ensure normal tissue repair. Utilizing a diabetic mouse model, it is demonstrated that PtCuTe significantly facilitated the regeneration of highly vascularized skin, with the percentage of wound closure being over 90% on the 8th day, which is the best among the reported comparable multifunctional biomaterials.

OBJECTIVE: To test whether the use of (i) particulated bone substitute + collagen membrane used for guided bone regeneration (GBR) of peri-implant bone defects renders different results from (ii) particulated bone substitute + collagen membrane + fixation pins and from (iii) block bone substitute + collagen membrane with respect to the volume stability of the augmented region during suturing of mucosal flaps. MATERIAL AND METHODS: Twenty peri-implant box-shaped bone defects were created in 10 pig mandibles. Every bone defect was augmented once with each of the following GBR procedures: Granulate (particulated xenograft + collagen membrane), Granulate + Pins (particulated xenograft + collagen membrane + fixation pins), and Block (block xenograft + collagen membrane). Cone-beam computed tomography scans were obtained prior and after blinded wound closure. The horizontal thickness (HT) of the augmented region (bone substitute + membrane) was assessed at the implant shoulder (HT0 mm ) and at 1-5 mm apical to the implant shoulder (HT1 mm -HT5 mm ). The changes of HT during flap suturing were calculated as absolute (mm) and relative values (%). Repeated-measures ANOVA was used for statistical analysis. RESULTS: Wound closure induced a statistically significant change of HT0 mm and of HT1 mm in all the treatment groups (P ≤ 0.05). The change in HT0 mm measured -42.8 ± 17.9% (SD) for Granulate, -22.9 ± 21.2% (SD) for Granulate + Pins, and -20.2 ± 18.9% (SD) for Block. The reduction in HT0 mm, HT1 mm , HT2 mm, and HT3 mm for the Granulate procedure was significantly higher as compared to the Granulate + Pins and the Block procedures (P ≤ 0.05). There were no statistically significant differences in the change of HT between the Granulate + Pins and the Block procedures (P > 0.05). CONCLUSION: Wound closure induced displacement of the bone substitute resulting in a partial collapse of the collagen membrane in the coronal portion of the augmented site. The stability of the bone substitute and collagen membrane was enhanced by the application of fixation pins and by the use of block bone substitute instead of particulated bone substitute.

BACKGROUND: Bone marrow-derived mesenchymal stem cell (BMSC) transplantation is considered a promising therapeutic approach for bone defect repair. However, during the transplantation procedure, the functions and viability of BMSCs may be impaired due to extended durations of in vitro culture, aging, and disease conditions of patients. Inspired by spontaneous intercellular mitochondria transfer that naturally occurs within injured tissues to rescue cellular or tissue function, we investigated whether artificial mitochondria transfer into pre-transplant BMSCs in vitro could improve cellular function and enhance their therapeutic effects on bone defect repair in situ. METHODS: Mitochondria were isolated from donor BMSCs and transferred into recipient BMSCs of the same batch and passage. Subsequently, changes in proliferative capacity and cell senescence were evaluated by live cell imaging, Cell Counting Kit-8 assay, cell cycle analysis, Ki67 staining, qPCR and Western blot analysis of c-Myc expression, and β-galactosidase staining. Migration ability was evaluated by the transwell migration assay, wound scratch healing, and cell motility tests. Alkaline phosphatase (ALP) staining, Alizarin Red staining, and combined with qPCR and Western blot analyses of Runx2 and BMP2 were performed to elucidate the effects of mitochondria transfer on the osteogenic potential of BMSCs in vitro. After that, in vivo experiments were performed by transplanting mitochondria-recipient BMSCs into a rat cranial critical-size bone defect model. Micro CT scanning and histological analysis were conducted at 4 and 8 weeks after transplantation to evaluate osteogenesis in situ. Finally, in order to establish the correlation between cellular behavioral changes and aerobic metabolism, OXPHOS (oxidative phosphorylation) and ATP production were assessed and inhibition of aerobic respiration by oligomycin was performed. RESULTS: Mitochondria-recipient BMSCs exhibited significantly enhanced proliferation and migration, and increased osteogenesis upon osteogenic induction. The in vivo results showed more new bone formation after transplantation of mitochondria-recipient BMSCs in situ. Increased OXPHOS activity and ATP production were observed, which upon inhibition by oligomycin attenuated the enhancement of proliferation, migration, and osteogenic differentiation induced by mitochondria transfer. CONCLUSIONS: Mitochondria transfer is a feasible technique to enhance BMSC function in vitro and promote bone defect repair in situ through the upregulation of aerobic metabolism. The results indicated that mitochondria transfer may be a novel promising technique for optimizing stem cell therapeutic function.

Reprogramming has been shown to involve EMT-MET; however, its role in cell differentiation is unclear. We report here that in vitro differentiation of hESCs to hepatic lineage undergoes a sequential EMT-MET with an obligatory intermediate mesenchymal phase. Gene expression analysis reveals that Activin A-induced formation of definitive endoderm (DE) accompanies a synchronous EMT mediated by autocrine TGFβ signalling followed by a MET process. Pharmacological inhibition of TGFβ signalling blocks the EMT as well as DE formation. We then identify SNAI1 as the key EMT transcriptional factor required for the specification of DE. Genetic ablation of SNAI1 in hESCs does not affect the maintenance of pluripotency or neural differentiation, but completely disrupts the formation of DE. These results reveal a critical mesenchymal phase during the acquisition of DE, highlighting a role for sequential EMT-METs in both differentiation and reprogramming.

ABSTRACT Metastasis‐associated lung adenocarcinoma transcript 1 ( Malat1 ) is an example of a functional long noncoding RNA involved in many biologic processes. However, the mechanisms for Malat1 in myogenesis are unclear. Serum response factor (SRF) is a pivotal transcription factor for muscle proliferation and differentiation and is reported to be a target gene for muscle‐specific microRNA‐133 (miR‐133). In this study, we initially found that silencing Malat1 in the mouse myoblast C2C12 cell line inhibited myocyte differentiation and decreased Srf at both the RNA and protein levels. Srf silencing decreased Malat1 expression as well. Further study revealed that Malat1 contained an miR‐133 functional target site, and the interplay between Malat1 and Srf was miR‐133 dependent. We demonstrated that Malat1 modulates Srf through miR‐133 as a competing endogenous RNA and established a novel connection among Malat1 , miR‐133, and Srf in myoblast differentiation.— Han, X., Yang, F., Cao, H., Liang. Z. Malat1 regulates serum response factor through miR‐133 as a competing endogenous RNA in myogenesis. FASEB J . 29, 3054‐3064 (2015). www.fasebj.org

Abstract Recently, single‐atom nanozymes have made significant progress in the fields of sterilization and treatment, but their catalytic performance as substitutes for natural enzymes and drugs is far from satisfactory. Here, a method is reported to improve enzyme activity by adjusting the spatial position of a single‐atom site on the nanoplatforms. Two types of Cu single‐atom site nanozymes are synthesized in the interlayer (Cu L /PHI) and in‐plane (Cu P /PHI) of poly (heptazine imide) (PHI) through different synthesis pathways. Experimental and theoretical analysis indicates that the interlayer position of PHI can effectively adjust the coordination number, coordination bond length, and electronic structure of Cu single atoms compared to the in‐plane position, thereby promoting photoinduced electron migration and O 2 activation, enabling effective generate reactive oxygen species (ROS). Under visible light irradiation, the photocatalytic bactericidal activity of Cu L /PHI against aureus is ≈100%, achieving the same antibacterial effect as antibiotics, after 10 min of low‐dose light exposure and 2 h of incubation.

AIM: To investigate the new tissues growing into the pulp space of immature dog teeth that were infected, disinfected and filled with blood clot (BC), dental pulp cells (DPCs), platelet-rich plasma (PRP) or a combination of DPCs and PRP in immature dog teeth with apical periodontitis. METHODOLOGY: Fifty-six immature roots from mandibular premolars of four beagles were divided into four experimental groups (n = 40) and two control groups. After the induction of apical periodontitis, the root canals of experimental groups were disinfected with NaOCl irrigation and a tri-antibiotic paste medication. The canals were then filled with different materials according to the experimental group: BC group, DPCs group, PRP group or DPCs + PRP group. Access cavities were sealed with MTA and composite. Radiographs were taken after 90 days, and the jaws including the teeth were processed for histologic analysis. The data were statistically analysed using chi-square evaluation and Student's t-test. RESULTS: Radiographic analyses demonstrated no significant difference between experimental groups in periradicular bone healing (P > 0.05), whilst those groups that used DPCs produced a significantly greater root thickening (P < 0.01). The histologic evaluation showed that the groups with PRP formed more tissues in the canals (P = 0.01). The groups with DPCs had substantially more mineralized tissue formation in the canal than those without DPCs, especially in the apical third. In DPCs + PRP group, bone-like tissue grew into the canal space from the periapical tissue. CONCLUSIONS: A combination of DPCs + PRP increased vital tissue regeneration within the root canals of immature teeth associated with apical periodontitis.

Angiogenesis is a critical aspect of wound healing. We investigated the role of keratinocytes in promoting angiogenesis in mice with lineage-specific deletion of the transcription factor FOXO1. The results indicate that keratinocyte-specific deletion of Foxo1 reduces VEGFA expression in mucosal and skin wounds and leads to reduced endothelial cell proliferation, reduced angiogenesis, and impaired re-epithelialization and granulation tissue formation. In vitro FOXO1 was needed for VEGFA transcription and expression. In a porcine dermal wound-healing model that closely resembles healing in humans, local application of a FOXO1 inhibitor reduced angiogenesis. This is the first report that FOXO1 directly regulates VEGFA expression and that FOXO1 is needed for normal angiogenesis during wound healing. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

AIM: The aim of this study was to investigate the accuracy of cone-beam computed tomography (CBCT) in assessing maxillary molar furcation involvement (FI). MATERIALS AND METHODS: Fifteen patients with generalized chronic periodontitis after initial therapy were recruited. CBCT was performed in maxillary molars with probing pocket depths of ≥6 mm and advanced FI, and CBCT images were analysed. Furcation surgery was performed in 20 maxillary molars. Lastly, intra-surgical FI assessments were compared with CBCT-based data. RESULTS: Intra-surgical findings confirmed 82.4% of the CBCT data, with a weighted kappa of 0.917. The agreement between both assessments was the highest in buccal furcation entrances, followed by distopalatal and mesiopalatal furcation entrances. Of the four parameters tested of detailed root anatomy and furcation morphology, the mean length of the root trunk and the width of the furcation entrance revealed by CBCT were consistent with their respective intra-surgical values (p > 0.05). Horizontal bone loss and vertical bone loss were underestimated by CBCT relative to their respective intra-surgical classifications (p ≤ 0.05). CONCLUSIONS: Cone-beam computed tomography images demonstrate a high accuracy in assessing the loss of periodontal tissue of the FI and root morphologies in maxillary molars.

Tooth whitening has recently become one of the most popular aesthetic dentistry procedures. Beyond classic hydrogen peroxide-based whitening agents, photo-catalysts and piezo-catalysts have been demonstrated for non-destructive on-demand tooth whitening. However, their usage has been challenged due to the relatively limited physical stimuli of light irradiation and ultrasonic mechanical vibration. To address this challenge, we report here a non-destructive and convenient tooth whitening strategy based on the pyro-catalysis effect, realized via ubiquitous oral motion-induced temperature fluctuations. Degradation of organic dyes via pyro-catalysis is performed under cooling/heating cycling to simulate natural temperature fluctuations associated with intake and speech. Teeth stained by habitual beverages and flavorings can be whitened by the pyroelectric particles-embedded hydrogel under a small surrounding temperature fluctuation. Furthermore, the pyro-catalysis-based tooth whitening procedure exhibits a therapeutic biosafety and sustainability. In view of the exemplary demonstration, the most prevalent oral temperature fluctuation will enable the pyro-catalysis-based tooth whitening strategy to have tremendous potential for practical applications.

While the application of computer-assisted maxillofacial surgery becomes increasingly popular, the translation from virtual models and surgical plans to actual bedside maneuvers and the evaluation of the repeatability of virtual planning remain to be major challenges. The objective of this study was to experiment the technique of using a resin template as a messenger in maxillofacial reconstruction involving a fibula flap. Another aim was to find a quantitative and objective method to evaluate the repeatability of preoperative planning. Seven patients who underwent maxillary or mandibular reconstruction were included in this study. The mean age was 25 years, and the mean follow-up period was 18.7 months. Virtual planning was carried out before surgery. A resin template was made according to the virtual design of bone graft through rapid prototyping technique and served as a guide when surgeons shaped the fibula flap during surgery. The repeatability of the virtual plan was evaluated based on the matching percentage between the actual postoperative model and the computer-generated outcome. All patients demonstrated satisfactory clinical outcomes. The mean repeatability was 87.5% within 1 mm and 96.5% within 2 mm in isolated bone graft. It was 71.4% within 1 mm and 89.9% within 2 mm in reconstructed mandible or maxilla. These results demonstrated that a resin template based on virtual plan and rapid prototyping technique is a reliable messenger to translate from computer modeling to bedside surgical procedures. The repeatability of a virtual plan can be easily and quantitatively evaluated through our three-dimensional differential analysis method.

Dental radiography provides important evidence for clinical diagnosis, treatment and quality evaluation. Much effort has been spent on developing digitalized dental X-ray image analysis systems for clinical quality improvement. In this paper, we present the datasets, procedures, and results conducted to evaluate dental treatment qualities using periapical dental X-ray images taken before and after the operations. In order to support dentists to make clinical decisions, we propose a tool pipeline for automated clinical quality evaluation. We build a dataset with 196 patients' periapical dental radiography images before and after the treatments. Radiography images are labelled as cases that are `getting better', `getting worse' and `have no explicit change' by designated dental experts. Our proposal includes an automatic method with the medical knowledge to crop the ROIs for clinical evaluation - the apical adjacent regions, and then pairs of ROIs are fed into a CNN to train the model for automated clinical quality evaluation. Our approach achieves the F1 score of 0.749, which is comparable to the performance of expert dentists and radiologists.

MiR-34a was demonstrated to be upregulated during the osteogenic differentiation of human adipose-derived stem cells (hASCs). Overexpression of miR-34a significantly increased alkaline phosphatase activity, mineralization capacity, and the expression of osteogenesis-associated genes in hASCs in vitro. Enhanced heterotopic bone formation in vivo was also observed upon overexpression of miR-34a in hASCs. Mechanistic investigations revealed that miR-34a inhibited the expression of retinoblastoma binding protein 2 (RBP2) and reduced the luciferase activity of reporter gene construct comprising putative miR-34a binding sites in the 3' UTR of RBP2. Moreover, miR-34a downregulated the expression of NOTCH1 and CYCLIN D1 and upregulated the expression of RUNX2 by targeting RBP2, NOTCH1, and CYCLIN D1. Taken together, our results suggested that miR-34a promotes the osteogenic differentiation of hASCs via the RBP2/NOTCH1/CYCLIN D1 coregulatory network, indicating that miR-34a-targeted therapy could be a valuable approach to promote bone regeneration.

Macrophages play a pivotal role in the immunological cascade activated in response to biomedical implants, which predetermine acceptance or rejection of implants by the host via pro- and anti-inflammatory polarisation states. The role of chemical signals in macrophage polarisation is well-established, but how physical cues regulate macrophage function that may play a fundamental role in implant-bone interface, remains poorly understood. Here we find that bone marrow-derived macrophages (BMDM) cultured on polyacrylamide gels of varying stiffness exhibit different polarisation states. BMDM are 'primed' to a pro-inflammatory M1 phenotype on stiff substrates, while to an anti-inflammatory M2 phenotype on soft and medium stiffness substrates. It is further observed that matrix stiffening increases Piezo1 expression, as well as leads to subsequent activation of the mechanotransduction signalling effector YAP, thus favouring M1 polarisation whilst suppressing M2 polarisation. Moreover, upon treatment with YAP inhibitor, we successfully induce macrophage re-polarisation to the M2 state within the implant site microenvironment, which in turn promotes implant osseointegration. Collectively, our present study thus characterises the critical role of the Piezo1-YAP signalling axis in macrophage mechanosensing and stiffness-mediated macrophage polarisation and provides cues for the design of immuno-modulatory biomaterials that can regulate the macrophage phenotype.

INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition. Forty-two cases with immunoglobulin G4-related sialadenitis (IgG4-RS) confirmed by histopathological and immunohistochemical assessment were studied to clarify the clinicopathologic characteristics of the salivary glands involved in IgG4-RS, especially the relationship between the histopathologic features and function of salivary glands or serum levels of IgG4. METHODS: Clinical, serologic, imaging and histopathological data of these cases were analyzed. CT volumes of submandibular, parotid, and lacrimal glands were calculated. The saliva flow rate was measured. Scintigraphy with 99mTc-pertechnetate was undertaken in 31 cases, and the concentration index (CI) and secretion index (SI) was calculated. Relationships between fibrosis severity and salivary gland function or serum IgG4 levels were analyzed. RESULTS: The first symptom was swelling of bilateral submandibular or lacrimal glands. Physical examination showed multiple bilateral major salivary glands (including sublingual and accessory parotid glands) and lacrimal glands were enlarged in IgG4 RS. Multiple enlarged cervical lymph nodes were noted in 30 patients. Saliva flow at rest was lower than normal in 34 cases; stimulated saliva flow was lower than normal in 15 cases. Secretory function was reduced more severely in the submandibular glands than in the parotid glands. Serum levels of IgG4 were elevated in 95.2% of cases and 78.6% patients had increased IgE levels. Serum IgG4 level was higher and saliva secretion lower as glandular fibrosis increased. CONCLUSIONS: Prominent changes in the morphology, histology, immunohistochemistry and secretion of the major salivary glands of IgG4-RS patients were accompanied by involvement of the lacrimal glands and cervical lymph nodes. Elevated IgE, allergic history, eosinophil infiltration suggest allergic reactions as a potential pathogenesis of IgG4-RS. Severity of glandular fibrosis correlated with salivary function and serum levels of IgG4.

Understanding the bioelectrical properties of bone tissue is key to developing new treatment strategies for bone diseases and injuries, as well as improving the design and fabrication of scaffold implants for bone tissue engineering. The bioelectrical properties of bone tissue can be attributed to the interaction of its various cell lineages (osteocyte, osteoblast and osteoclast) with the surrounding extracellular matrix, in the presence of various biomechanical stimuli arising from routine physical activities; and is best described as a combination and overlap of dielectric, piezoelectric, pyroelectric and ferroelectric properties, together with streaming potential and electro-osmosis. There is close interdependence and interaction of the various electroactive and electrosensitive components of bone tissue, including cell membrane potential, voltage-gated ion channels, intracellular signaling pathways, and cell surface receptors, together with various matrix components such as collagen, hydroxyapatite, proteoglycans and glycosaminoglycans. It is the remarkably complex web of interactive cross-talk between the organic and non-organic components of bone that define its electrophysiological properties, which in turn exerts a profound influence on its metabolism, homeostasis and regeneration in health and disease. This has spurred increasing interest in application of electroactive scaffolds in bone tissue engineering, to recapitulate the natural electrophysiological microenvironment of healthy bone tissue to facilitate bone defect repair.