The circadian clock in enamel development.

Circadian rhythms are self-sustaining oscillations within biological systems that play key roles in a diverse multitude of physiological processes. The circadian clock mechanisms in brain and peripheral tissues can oscillate independently or be synchronized/disrupted by external stimuli. Dental enamel is a type of mineralized tissue that forms the exterior surface of the tooth crown. Incremental Retzius lines are readily observable microstructures of mature tooth enamel that indicate the regulation of amelogenesis by circadian rhythms. Teeth enamel is formed by enamel-forming cells known as ameloblasts, which are regulated and orchestrated by the circadian clock during amelogenesis. This review will first examine the key roles of the circadian clock in regulating ameloblasts and amelogenesis. Several physiological processes are involved, including gene expression, cell morphology, metabolic changes, matrix deposition, ion transportation, and mineralization. Next, the potential detrimental effects of circadian rhythm disruption on enamel formation are discussed. Circadian rhythm disruption can directly lead to Enamel Hypoplasia, which might also be a potential causative mechanism of amelogenesis imperfecta. Finally, future research trajectory in this field is extrapolated. It is hoped that this review will inspire more intensive research efforts and provide relevant cues in formulating novel therapeutic strategies for preventing tooth enamel developmental abnormalities.

[Bionic design, preparation and clinical translation of oral hard tissue restorative materials].

Oral diseases concern almost every individual and are a serious health risk to the population. The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour. Based on the principle of "learning from the nature", Deng Xuliang's group of Peking University School and Hospital of Stomatology has proposed a new concept of "microstructural biomimetic design and tissue adaptation of tooth/jaw materials" to address the worldwide problems of difficulty in treating dentine hypersensitivity, poor prognosis of restoration of tooth defects, and vertical bone augmentation of alveolar bone after tooth loss. The group has broken through the bottleneck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects, and invented key technologies such as crystalline/amorphous multi-level assembly, ion-transportation blocking, and multi-physical properties of the micro-environment reconstruction, etc. The group also pioneered the cationic-hydrogel desensitizer, digital stump and core integrated restorations, and developed new crown and bridge restorative materials, gradient functionalisation guided tissue regeneration membrane, and electrically responsive alveolar bone augmentation restorative membranes, etc. These products have established new clinical strategies for tooth/jaw defect repair and achieved innovative results. In conclusion, the research results of our group have strongly supported the theoretical improvement of stomatology, developed the technical system of oral hard tissue restoration, innovated the clinical treatment strategy, and led the progress of the stomatology industry.

Fabrication of a novel aesthetic orthodontic bracket and evaluation of friction properties between PEEK and stainless steel wires.

BACKGROUND: Polyetheretherketone (PEEK) is a polyaromatic semi-crystalline thermoplastic polymer with mechanical and lubrication properties favorable for biomedical applications. Despite of its aesthetic appearance, ceramic brackets are unsatisfactory in brittleness and thickness, while PEEK is a potential material for aesthetic orthodontic brackets. OBJECTIVE: To fabricate a novel aesthetic orthodontic bracket and evaluate friction properties of PEEK and stainless steel wires. METHODS: All polyether ether ketone (PEEK) and ceramic samples disks were made into disks (diameter, 5 mm; thickness, 2 mm). The tested surfaces of PEEK were ground with #600, #800 and #1200 SiC papers, followed by polishing with Sof-Lex kit (3M ESPE, USA). The surface roughness was tested using a laser profilometer device (VK-X200, Keyence, Japan). The COFs of the specimens and stainless steel (SS) archwires were tested using a Universal Micro-Tribotester (UMT-3, Bruker, USA). The wear scratches on the materials' surfaces were examined by using a scanning electron microscope (SEM) (Hitachi SU8010). The elastic modulus and hardness of samples were examined with a nano-indenter (XP, Keysight Technologies, USA). RESULTS: The mean surface roughness of PEEK and Ceramic are 0.320 ± 0.028 µm and 0.343 ± 0.044 µm, respectively. PEEK has a lower Friction coefficient than Ceramic and the difference between the two groups was statistically significant (P< 0.05). The abrasive wear of Ceramic was the main wear style and was characterized by the observation of chipping fractures, while PEEK surface looked smooth without obvious scale-like desquamations and granular debris, indicating adhesive wear. CONCLUSION: Within the limitations of the present study, PEEK shows lower coefficient of friction than ceramic. PEEK has excellent properties such as low friction coefficient, smooth surface and good mechanical properties, and thus meets the requirements for orthodontic brackets. It is considered as a potential bracket material with both low friction and aesthetic performance.

The Deubiquitinase OTUD1 Suppresses Secretory Neutrophil Polarization And Ameliorates Immunopathology of Periodontitis.

Tissue-infiltrating neutrophils (TINs) secrete various signaling molecules to establish paracrine communication within the inflammatory milieu. It is imperative to identify molecular mediators that control this secretory phenotype of TINs. The present study uncovers a secretory neutrophil subset that exhibits increased pro-inflammatory cytokine production and enhanced migratory capacity which is highly related with periodontal pathogenesis. Further analysis identifies the OTU domain-containing protein 1 (OTUD1) plays a regulatory role in this secretory neutrophil polarization. In human and mouse periodontitis, the waning of inflammation is correlated with OTUD1 upregulation, whereas severe periodontitis is induced when neutrophil-intrinsic OTUD1 is depleted. Mechanistically, OTUD1 interacts with SEC23B, a component of the coat protein II complex (COPII). By removing the K63-linked polyubiquitin chains on SEC23B Lysine 81, the deubiquitinase OTUD1 negatively regulates the COPII secretory machinery and limits protein ER-to-Golgi trafficking, thus restricting the surface expression of integrin-regulated proteins, CD9 and CD47. Accordingly, blockade of protein transport by Brefeldin A (BFA) curbs recruitment of Otud1-deficient TINs and attenuates inflammation-induced alveolar bone destruction. The results thus identify OTUD1 signaling as a negative feedback loop that limits the polarization of neutrophils with secretory phenotype and highlight the potential application of BFA in the treatment of periodontal inflammation.

A novel dice-inspired multifunctional 3D printing guided splint for minimally invasive access cavity preparation and canal orifice identification.

BACKGROUND: The minimally invasive endodontics could retain more peri-cervical dentin (PCD) and other important dental structures, thus realizing the minimal loss of teeth structures and preserving the strength and function of the endodontically treated tooth (ETT). The search for abnormal root canals or calcified root canals could be quite time-consuming and increase the risk of perforation. OBJECTIVE: This study introduced a novel multifunctional 3D printing guided splint inspired by the dice, which can achieve the minimally invasive access cavity preparation and canal orifice identification. METHOD: Data were collected from an outpatient with dens invaginatus. Cone-beam Computed Tomography (CBCT) revealed a type III invagination. The CBCT data of the patient were imported into a computer-aided design (CAD) software (Exocad 3.0; Exocad GmbH) for the 3D reconstruction of jaw bones and teeth. The dice-inspired 3D printing guided splint consists of the sleeve and guided splint. The sleeve with minimal invasive opening channel and orifice locating channel were designed with a reverse-engineering software (Geomagic Wrap 2021). The reconstructed models in the Standard Template Library (STL) format were imported into a CAD software. The design of the template was aided by the dental CAD software in Splint Design Mode. The sleeve and splint were exported into the STL files separately. A 3D printer (ProJet® 3600 3D Systems) was used to separately generate the sleeve and guided splint, and was made by stereolithography and processed in a medical resin (VisiJet M3 StonePlast). RESULTS: The novel multifunctional 3D printing guided splint could be set in position. The opening side in the sleeve was selected and the sleeve was inserted in place. The minimal invasive opening was made in the crown of the tooth to access the pulp. The sleeve was draw out and turned to the orifice location side, and then inserted in place. The target orifice was located rapidly. CONCLUSION: This novel dice-inspired multifunctional 3D printing guided splint allow dental practitioners to gain accurate, conservative, and safe cavity access from teeth with anatomical malformations. Complex operations might be carried out with less reliance on the operator's experience than with conventional access preparations. This novel dice-inspired multifunctional 3D printing guided splint would have a broad application in the dental field.

Correction: Restoring the electrical microenvironment using ferroelectric nanocomposite membranes to enhance alveolar ridge regeneration in a mini-pig preclinical model.

Correction for 'Restoring the electrical microenvironment using ferroelectric nanocomposite membranes to enhance alveolar ridge regeneration in a mini-pig preclinical model' by Yiping Li et al., J. Mater. Chem. B, 2023, 11, 985-997, https://doi.org/10.1039/D2TB02054H.

The bioelectrical properties of bone tissue.

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.

Manipulation of Heterogeneous Surface Electric Potential Promotes Osteogenesis by Strengthening RGD Peptide Binding and Cellular Mechanosensing.

The heterogeneity of extracellular matrix (ECM) topology, stiffness, and architecture is a key factor modulating cellular behavior and osteogenesis. However, the effects of heterogeneous ECM electric potential at the micro- and nanoscale on osteogenesis remain to be elucidated. Here, the heterogeneous distribution of surface potential is established by incorporating ferroelectric BaTiO3 nanofibers (BTNF) into poly(vinylidene fluoridetrifluoroethylene) (P(VDF-TrFE)) matrix based on phase-field and first-principles simulation. By optimizing the aspect ratios of BTNF fillers, the anisotropic distribution of surface potential on BTNF/P(VDF-TrFE) nanocomposite membranes can be achieved by strong spontaneous electric polarization of BTNF fillers. These results indicate that heterogeneous surface potential distribution leads to a meshwork pattern of fibronectin (FN) aggregation, which increased FN-III7-10 (FN fragment) focal flexibility and anchor points as predicted by molecular dynamics simulation. Furthermore, integrin clustering, focal adhesion formation, cell spreading, and adhesion are enhanced sequentially. Increased traction of actin fibers amplifies mechanotransduction by promoting nuclear translocation of YAP/Runx2, which enhances osteogenesis in vitro and bone regeneration in vivo. The work thus provides fundamental insights into the biological effects of surface potential heterogeneity at the micro- and nanoscale on osteogenesis, and also develops a new strategy to optimize the performance of electroactive biomaterials for tissue regenerative therapies.

Electroactive Biomaterials for Facilitating Bone Defect Repair under Pathological Conditions.

Bone degeneration associated with various diseases is increasing due to rapid aging, sedentary lifestyles, and unhealthy diets. Living bone tissue has bioelectric properties critical to bone remodeling, and bone degeneration under various pathological conditions results in significant changes to these bioelectric properties. There is growing interest in utilizing biomimetic electroactive biomaterials that recapitulate the natural electrophysiological microenvironment of healthy bone tissue to promote bone repair. This review first summarizes the etiology of degenerative bone conditions associated with various diseases such as type II diabetes, osteoporosis, periodontitis, osteoarthritis, rheumatoid arthritis, osteomyelitis, and metastatic osteolysis. Next, the diverse array of natural and synthetic electroactive biomaterials with therapeutic potential are discussed. Putative mechanistic pathways by which electroactive biomaterials can mitigate bone degeneration are critically examined, including the enhancement of osteogenesis and angiogenesis, suppression of inflammation and osteoclastogenesis, as well as their anti-bacterial effects. Finally, the limited research on utilization of electroactive biomaterials in the treatment of bone degeneration associated with the aforementioned diseases are examined. Previous studies have mostly focused on using electroactive biomaterials to treat bone traumatic injuries. It is hoped that this review will encourage more research efforts on the use of electroactive biomaterials for treating degenerative bone conditions.

Restoring the electrical microenvironment using ferroelectric nanocomposite membranes to enhance alveolar ridge regeneration in a mini-pig preclinical model.

The maintenance and incremental growth of the alveolar bone at the tooth extraction site, to achieve the required height and width for implant restoration, remains a major clinical challenge. Here, the concept of restoring the electrical microenvironment to improve the effects of alveolar ridge preservation (ARP) was investigated in a mini-pig preclinical model. The endogeneous electrical microenvironment of the dental alveolar socket was recapitulated by fabricating a biomimetic ferroelectric BaTiO3/poly(vinylidene fluoridetrifluoroethylene) (BTO/P(VDF-TrFE)) non-resorbable nanocomposite membrane polarized by corona poling. The polarized nanocomposite membrane exhibited excellent electrical stability. After implantation with bone grafts and covering with the charged membrane in tooth extraction sites for three months, both the vertical and horizontal dimension resorption of the alveolar ridge were significantly prevented, as assessed by cone beam computed tomography (CBCT) analyses. Micro-CT analysis showed that the charged membrane induced significant enhancement of newly regenerated bone at the tooth extraction sites. Histological analysis further confirmed that the restoration of the electrical microenvironment significantly promoted buccal alveolar bone regeneration and maturation. In addition, the charged membranes can maintain their structural integrity during the entire implantation period and exhibit positive long-term systemic safety, as assessed by preclinical sub-chronic systemic toxicity. These findings thus provide an innovative strategy for restoring the electrical microenvironment to enhance ARP following dentition defect and edentulism, which could further advance prosthodontics implant technology.

Electrical charge on ferroelectric nanocomposite membranes enhances SHED neural differentiation.

Stem cells from human exfoliated deciduous teeth (SHED) uniquely exhibit high proliferative and neurogenic potential. Charged biomaterials have been demonstrated to promote neural differentiation of stem cells, but the dose-response effect of electrical stimuli from these materials on neural differentiation of SHED remains to be elucidated. Here, by utilizing different annealing temperatures prior to corona poling treatment, BaTiO3/P(VDF-TrFE) ferroelectric nanocomposite membranes with varying charge polarization intensity (d 33 ≈ 0, 4, 12 and 19 pC N-1) were fabricated. Enhanced expression of neural markers, increased cell elongation and more prominent neurite outgrowths were observed with increasing surface charge of the nanocomposite membrane indicating a dose-response effect of surface electrical charge on SHED neural differentiation. Further investigations of the underlying molecular mechanisms revealed that intracellular calcium influx, focal adhesion formation, FAK-ERK mechanosensing pathway and neurogenic-related ErbB signaling pathway were implicated in the enhancement of SHED neural differentiation by surface electrical charge. Hence, this study confirms the dose-response effect of biomaterial surface charge on SHED neural differentiation and provides preliminary insights into the molecular mechanisms and signaling pathways involved.

Pyro-catalysis for tooth whitening via oral temperature fluctuation.

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.

Biomimetic hierarchical implant surfaces promote early osseointegration in osteoporotic rats by suppressing macrophage activation and osteoclastogenesis.

Successful implant-bone integration remains a formidable challenge in osteoporotic patients, because of excessive inflammatory reactions and osteoclastogenesis around the peri-implant bone tissue. This study designed biomimetic micro/sub-micro hierarchical surfaces on titanium implants based on natural bone hierarchical structures to mitigate macrophage-mediated inflammatory reactions, osteoclastogenesis, and osteogenesis in vitro, as well as promote early osseointegration in vivo. It was found that the biomimetic hierarchical surfaces inhibited M1 macrophage-mediated inflammatory reactions via suppression of the TLR2/NF-κB signaling pathway in vitro. Subsequently, osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was observed to be significantly enhanced on hierarchical surfaces in the presence of macrophage conditional media. Furthermore, osteoclast formation was also decreased by inhibiting the osteoclastogenesis regulatory factor NFATc-1 expression on hierarchical surfaces. In vivo, the implant with a micro/sub-micro hierarchical surface underwent rapid and early osseointegration, with the newly formed bone being tightly integrated with the implants. Hence, the hierarchical surface mitigated the inflammatory microenvironment around the implant, thereby inhibiting osteoclastogenesis. This study thus offers a novel biomimetic strategy for designing surface hierarchical topography to facilitate implant-bone osseointegration in osteoporotic patients.

Extrapolating neurogenesis of mesenchymal stem/stromal cells on electroactive and electroconductive scaffolds to dental and oral-derived stem cells.

The high neurogenic potential of dental and oral-derived stem cells due to their embryonic neural crest origin, coupled with their ready accessibility and easy isolation from clinical waste, make these ideal cell sources for neuroregeneration therapy. Nevertheless, these cells also have high propensity to differentiate into the osteo-odontogenic lineage. One strategy to enhance neurogenesis of these cells may be to recapitulate the natural physiological electrical microenvironment of neural tissues via electroactive or electroconductive tissue engineering scaffolds. Nevertheless, to date, there had been hardly any such studies on these cells. Most relevant scientific information comes from neurogenesis of other mesenchymal stem/stromal cell lineages (particularly bone marrow and adipose tissue) cultured on electroactive and electroconductive scaffolds, which will therefore be the focus of this review. Although there are larger number of similar studies on neural cell lines (i.e. PC12), neural stem/progenitor cells, and pluripotent stem cells, the scientific data from such studies are much less relevant and less translatable to dental and oral-derived stem cells, which are of the mesenchymal lineage. Much extrapolation work is needed to validate that electroactive and electroconductive scaffolds can indeed promote neurogenesis of dental and oral-derived stem cells, which would thus facilitate clinical applications in neuroregeneration therapy.

Bone Piezoelectricity-Mimicking Nanocomposite Membranes Enhance Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by Amplifying Cell Adhesion and Actin Cytoskeleton.

Ferroelectric biomaterials have been widely investigated and demonstrated to enhance osteogenesis by simulating the inherent electrical properties of bone tissues. Nevertheless, the underlying biological processes are still not wellunderstood. Hence, this study investigated the underlying biological processes by which bone piezoelectricity-mimicking barium titanate/poly(vinylidene fluoride-trifluoroethylene) nanocomposite membranes (BTO nanocomposite membranes) promote osteogenesis of Bone Marrow Mesenchymal Stem Cells (BMSCs). Ourresults revealed that the piezoelectric coefficient (d33) of nanocomposite membranes aftercontrolled corona poling was similar to that of native bone, and exhibited highly-stable piezoelectrical properties and concentrated surface electrical potential. These nanocomposite membranes significantly enhanced the adhesion and spreading of BMSCs, which was manifested as increased number and area of mature focal adhesions. Furthermore, the nanocomposite membranes significantly promoted the expression of integrin receptors genes (α1, α5 andß3), which in turn enhanced osteogenesis of BMSCs, as manifested by upregulated Alkaline Phosphatase (ALP) and Bone Morphogenetic Protein 2 (BMP2) expression levels. Further investigations found that the Focal Adhesion Kinase (FAK)-Extracellular Signal-Regulated Kinase1/2 (ERK 1/2) signaling axis may be involved in the biological process of polarized nanocomposite membrane-induced osteogenesis. This study thus provides useful insights for betterunderstanding of the biological processes by which piezoelectric or ferroelectric biomaterials promote osteogenesis.

Restoration of electrical microenvironment enhances bone regeneration under diabetic conditions by modulating macrophage polarization.

Macrophage-mediated inflammation compromises bone repair in diabetic patients. Electrical signaling cues are known to regulate macrophage functions. However, the biological effects of electrical microenvironment from charged biomaterials on the immune response for regulating osteogenesis under diabetic conditions remain to be elucidated. Herein the endogeneous electrical microenvironment of native bone tissue was recapitulated by fabricating a ferroelectric BaTiO3/poly (vinylidene fluoridetrifluoroethylene) (BTO/P(VDF-TrFE)) nanocomposite membrane. In vitro, the polarized BaTiO3/poly (vinylidene fluoridetrifluoroethylene) (BTO/P(VDF-TrFE)) nanocomposite membranes inhibited high glucose-induced M1-type inflammation, by effecting changes in cell morphology, M1 marker expression and pro-inflammatory cytokine secretion in macrophages. This led to enhanced osteogenic differentiation of human bone marrow mesenchymal stem cells (BM-MSCs). In vivo, the biomimetic electrical microenvironment recapitulated by the polarized nanocomposite membranes switched macrophage phenotype from the pro-inflammatory (M1) into the pro-healing (M2) phenotype, which in turn enhanced bone regeneration in rats with type 2 diabetes mellitus. Mechanistic studies revealed that the biomimetic electrical microenvironment attenuated pro-inflammatory M1 macrophage polarization under hyperglycemic conditions by suppressing expression of AKT2 and IRF5 within the PI3K-AKT signaling pathway, thereby inducing favorable osteo-immunomodulatory effects. Our study thus provides fundamental insights into the biological effects of restoring the electrical microenvironment conducive for osteogenesis under DM conditions, and offers an effective strategy to design functionalized biomaterials for bone regeneration therapy in diabetic patients.

An overview of signaling pathways regulating YAP/TAZ activity.

YAP and TAZ are ubiquitously expressed homologous proteins originally identified as penultimate effectors of the Hippo signaling pathway, which plays a key role in maintaining mammalian tissue/organ size. Presently, it is known that YAP/TAZ also interact with various non-Hippo signaling pathways, and have diverse roles in multiple biological processes, including cell proliferation, tissue regeneration, cell lineage fate determination, tumorigenesis, and mechanosensing. In this review, we first examine the various microenvironmental cues and signaling pathways that regulate YAP/TAZ activation, through the Hippo and non-Hippo signaling pathways. This is followed by a brief summary of the interactions of YAP/TAZ with TEAD1-4 and a diverse array of other non-TEAD transcription factors. Finally, we offer a critical perspective on how increasing knowledge of the regulatory mechanisms of YAP/TAZ signaling might open the door to novel therapeutic applications in the interrelated fields of biomaterials, tissue engineering, regenerative medicine and synthetic biology.

Role of YAP/TAZ in Cell Lineage Fate Determination and Related Signaling Pathways.

The penultimate effectors of the Hippo signaling pathways YAP and TAZ, are transcriptional co-activator proteins that play key roles in many diverse biological processes, ranging from cell proliferation, tumorigenesis, mechanosensing and cell lineage fate determination, to wound healing and regeneration. In this review, we discuss the regulatory mechanisms by which YAP/TAZ control stem/progenitor cell differentiation into the various major lineages that are of interest to tissue engineering and regenerative medicine applications. Of particular interest is the key role of YAP/TAZ in maintaining the delicate balance between quiescence, self-renewal, proliferation and differentiation of endogenous adult stem cells within various tissues/organs during early development, normal homeostasis and regeneration/healing. Finally, we will consider how increasing knowledge of YAP/TAZ signaling might influence the trajectory of future progress in regenerative medicine.

Integrating silicon/zinc dual elements with PLGA microspheres in calcium phosphate cement scaffolds synergistically enhances bone regeneration.

Integrating multiple pro-osteogenic factors into bone graft substitutes is a practical and effective approach to improve bone repair efficacy. Here, Si-Zn dual elements and PLGA microspheres were incorporated into calcium phosphate cement (CPC) scaffolds (PLGA/CPC-Si/Zn) as a novel strategy to synergistically enhance bone regeneration. The incorporation of PLGA microspheres and Si/Zn dual elements within CPC scaffolds improved the setting time, injectability and compressive strength. The PLGA/CPC-Si/Zn scaffolds displayed controlled sequential release of Si and Zn ions. In vitro, RAW 264.7 cells displayed the M2 phenotype with a high level of anti-inflammatory cytokines in response to PLGA/CPC-Si/Zn. The conditioned medium of RAW 264.7 cells cultured on the PLGA/CPC-Si/Zn scaffolds significantly enhanced the osteogenic differentiation of rat BMSCs. In a rat femur defect model, the implanted PLGA/CPC-Si/Zn scaffolds led to obvious new bone formation after 4 weeks, apparent bone ingrowth into the PLGA microspheres after 12 weeks, and was almost completely filled with mature new bone upon degradation of the PLGA microspheres at 24 weeks. These findings demonstrate that the PLGA/CPC-Si/Zn scaffolds promote osteogenesis by synergistically improving the immune microenvironment and biodegradability. Hence, integrating multiple trace elements together with degradable components within bone graft biomaterials can be an effective strategy for promoting bone regeneration.

Piezo-catalysis for nondestructive tooth whitening.

The increasing demand for a whiter smile has resulted in an increased popularity for tooth whitening procedures. The most classic hydrogen peroxide-based whitening agents are effective, but can lead to enamel demineralization, gingival irritation, or cytotoxicity. Furthermore, these techniques are excessively time-consuming. Here, we report a nondestructive, harmless and convenient tooth whitening strategy based on a piezo-catalysis effect realized by replacement of abrasives traditionally used in toothpaste with piezoelectric particles. Degradation of organic dyes via piezo-catalysis of BaTiO3 (BTO) nanoparticles was performed under ultrasonic vibration to simulate daily tooth brushing. Teeth stained with black tea, blueberry juice, wine or a combination thereof can be notably whitened by the poled BTO turbid liquid after vibration for 3 h. A similar treatment using unpoled or cubic BTO show negligible tooth whitening effect. Furthermore, the BTO nanoparticle-based piezo-catalysis tooth whitening procedure exhibits remarkably less damage to both enamel and biological cells.