Hydroxyapatite Crystals Research Articles

Morphology Control of Hydroxyapatite as a Potential Reinforcement for Orthopedic Biomaterials: The Hydrothermal Process

Hydroxyapatite (HAp) of different morphologies was prepared by the direct decomposition of calcium lactate pentahydrate chelates using dipotassium hydrogen phosphate under hydrothermal conditions. The proposed technique allows for precise control of the HAp crystals morphology and product purity, which are necessary for biomedical applications. The synthesis parameters such as reagent concentrations, pH, reaction time, temperature, pressure, and stirring rate were optimized in order to produce calcium phosphates (CaPs) ceramics with restricted morphologies and composition. As a result, we obtained hydroxyapatite in the form of whiskers, hexagonal rods, nano particles, flowers, and cylinders. The products were characterized according to their structure (FTIR and XRD), morphology (SEM), and functional properties, i.e., the specific surface area. The obtained results indicate that the reagent concentration and pH values have the greatest impact on the HAp properties; however, the proper combination of all the mentioned parameters should be considered when there is a need for a bioceramic with defined physicochemical properties and an appropriate morphology.

Effects of carbonate species and chloride ions on calcium phosphate nucleation of biological apatite

Apatite is the principal inorganic component of biological hard tissues such as bone and teeth, and thus is essential to the existence of vertebrate life. Because carbonate species and chloride ions are ubiquitous in the fluids of vertebrate life forms, and these species are known to compete with phosphate species, it is critical to understand the influence of these anions on the nucleation of biological apatite. In this study, the important roles of carbonate and chloride ions in mediating inorganic calcium phosphate (CaP) phase nucleation are revealed both theoretically and experimentally. Theoretical investigations suggest that the Ca-O coordination number is an important descriptor for the nucleation of CaP and the interface interaction of the CaP-additive. Positive surface charges on the outermost Ca2+ ions of CaP clusters could attract carbonate species and Cl− ions, promoting the formation of CaP phase. In the presence of carbonate species and Cl− ions, the crystallization of hydroxyapatite (HA) from its precursor brushite (DCPD) has been observed in our experimental studies. The Cl− ion-doped B-type HA is proposed to be the most likely biological apatite based on equilibrium oxygen isotope fractionation and vibrational spectroscopic analysis. The insight gained here may help rationalize the control of biomineralization, and will guide the synthesis of anion-doped biological functional apatite materials.

TRPM4: New actor in osteogenic differentiation of human valvular interstitial cells

Transient receptor potential melastatin 4 (TRPM4) protein, a non-selective cation channel activated by calcium, is involved in cardiac fibroblasts remodeling. Its expression was reported in human valvular interstitial cells (VIC) with similar properties than fibroblasts, and its protein expression is increased on calcified aortic valves from patients suffering of aortic stenosis. VIC osteogenic differentiation is a key element in valvular calcification, which is, at term, responsible of aortic stenosis. The purpose of this study is to evaluate the implication of TRPM4 in human VIC osteogenic differentiation. VIC are isolated by enzymatic digestion from human aortic valves obtained from patients undergoing surgical aortic valve replacement. They are maintained 14 days in procalcifying media (2.7 mM calcium/2.5 mM phosphate), with or without 9-phenanthrol, a pharmacological TRPM4 inhibitor. Channel expression and functionality were followed respectively by PCR, Western Blot and electrophysiological recordings in the inside-out configuration of the patch clamp technique. Osteogenic differentiation of VIC was evaluated by measuring hydroxyapatite crystals by Alizarin red staining and by monitoring the protein expression of the osteogenic markers, BMP2 and RUNX2. A typical TRPM4 current was detected on VIC: its current-voltage relationship was linear with a conductance of 20.3 pS; the channel exhibited similar permeability for Na+ and K+; it was more activated in positive voltages and with increasing concentrations of internal Ca2+; the current was dose-dependently inhibited by 9-phenanthrol. TRPM4 mRNA and protein expression on VIC was confirmed by PCR and Western Blot. When maintained in procalcifying media, VIC developed hydroxyapatite crystals. Application of 9-phenanthrol (3.10-6 M) reduced mineralization by 30% without affecting cell viability. Moreover, it significantly reduced BMP2 and RUNX2 expression. Thereby, TRPM4 participates in osteogenic differentiation of human VIC in culture. Next studies of our unit are to evaluate whether TRPM4 repression by shRNA confirms those results.

Inhibiting the phosphatase activity of soluble epoxide hydrolase attenuates chronic kidney disease-induced calcific aortic valve disease in rats

Calcific aortic valve disease (CAVD) is the most frequent valvulopathy ultimaltely leading to aortic stenosis, one of the driving causes of an increased morbidity and mortality in aging and in patients with chronic kidney disease (CKD). Up to date, there is no available pharmacological treatment to prevent the development and progression of CAVD. Previous studies suggested that the bifunctional enzyme, soluble epoxide hydrolase (sEH), is involved in the regulation of cardiovascular calcification development. Our study aimed to investigate whether the phosphatase activity of sEH is involved in CAVD. Sprague Dawley sEH-P knocking rats (sEH-P KI) were generated using CRISPR/Cas9 method. Eighteen-week-old WT and sEH-P KI rats underwent subtotal nephrectomy (5/6Nx) to mimic CKD. These animals were afterword fed with a high-phosphate chow diet (1.8% phosphorus). In parallel, sham-operated animals on a standard diet (0.9% total phosphorus) served as controls. Twelve weeks after surgery, renal and cardiac parameters were determined and histological analysis of aortic valves was performed. Twelve weeks after surgery, the development of renal dysfunction in 5/6Nx + phosphate WT rats was shown by the augmentation in plasma creatinine and urea nitrogen concentrations and the decline in estimated glomerular filtration rate compared to sham-operated WT rats. These animals also displayed anemia, polyuria and polydipsia. The genetic inhibition of sEH-P did not allow to prevent these alterations. However, inhibiting sEH-P limited hydroxyapatite crystals deposition in the aortic valve of 5/6Nx + phosphate rats compared to 5/6Nx + phosphate WT rats (Fig. 1B, C), associated with a prevention of the decrease in intercusp distance and of the increase in aortic valve mean pressure gradient and in peak aortic valve velocity (Fig. 1A). In addition, left-ventricular diastolic (E/e′) and systolic dysfunction (fractional shortening) as well as cardiac fibrosis were prevented by sEH-P inhibition. Additional experiments on recombinant human and rat sEH allowed to demonstrate that sEH-P metabolizes pyrophosphate anions (PPi), a potent inhibitor of cardiovascular calcification, and that PPi degradation is efficiently prevented by sEH-P inhibition. Taking altogether, these results demonstrate that inhibition of sEH-P prevents aortic valve calcification and its hemodynamical consequences in the 5/6Nx + phosphate rat model, and may serve as a potential therapeutic strategy for the treatment of CAVD.

Solution NMR structure of cementum protein 1 derived peptide (CEMP1-p1) and its role in the mineralization process.

We report the characterization of the three-dimensional structure of the CEMP1-p1 peptide [MGTSSTDSQQAQHRRCSTSN: corresponding to residues 1-20 of the N-terminus of cementum protein 1 (CEMP1)]. This peptide imitates the capacity of CEMP1 to stimulate hydroxyapatite (HA) crystal nucleation and growth, and promotes the differentiation of periodontal ligament cells into a cementoblastic phenotype. Additionally, in experimental models of critical-sized calvarial defects in Wistar rats, CEMP1-p1 has shown osteogenic properties that enhanced the physiological deposition and maturation of newly formed bone. In this work, studies of CEMP1-p1 by circular dichroism (CD) and nuclear magnetic resonance (NMR) were performed in trifluoroethanol D2 (TFED2) and aqueous solution to determine the 3D structure of the peptide. Using the 3D model, experimental data from HA crystals formation and calcium fluorescence emission, we explain the biological mechanisms involved in CEMP1-p1 activity to promote calcium recruitment and its affinity to HA crystals. This information is valuable because it proposes, for the first time, a plausible molecular mechanism during the mineralization process, from a specific cementum protein-derived peptide.

Effect of pectin on the crystallization of strontium substituted HA for bone reconstruction application

The biomacropolymers of bone extracellular matrix (ECM) guide the growth of hydroxyapatite (HA) with various ionic substitutions. Pectin, a plant polysaccharide with chemical similarities to ECM, was investigated for its potential to promote the crystallization of strontium-substituted HA (SH). The influence of pectin (0.5 and 1.0 wt%) on the in situ mineralization of SH (10 and 30 mol% calcium substitution with strontium) was studied. The preferential affinity of pectin to strontium over calcium favoured the incorporation of strontium in apatite, decreased crystal size (18.85–26.22 nm) and retained more pectin residues (8–16%). The residual pectin strongly interacted with small SH particles, resulting in high microhardness (0.43–0.85 GPa) and high surface charge (−32.1 to −30.3 mV), while weak interaction with large HA particles resulted in low microhardness (0.15–0.25 GPa) and low surface charge (−35.4 to −34.6 mV). The in vitro cellular study using human osteoblast-like MG-63 cells demonstrated that inorganic size and material crystallinity play a vital role in regulating osteogenesis. The study suggests that the synchronization of low pectin concentration (0.5 wt%) and high strontium substitution in HA (30 mol%) offers the desired microhardness and in vitro osteogenic properties to emulate natural bone.

In-Depth Occlusion of Dentinal Tubules and Rapid Remineralization of Demineralized Dentin Induced by Polyelectrolyte-Calcium Complexes.

Dentin hypersensitivity (DH) is triggered by external stimuli irking fluid flow through exposed dentinal tubules (DTs). Three commercially available desensitizing agents as control in this study only achieve limited occlusion depths of ≈10µm in the DTs as well as scarce remineralization of demineralized dentin matrix. Herein, polyelectrolyte-calcium complexes pre-precursor (PCCP) process is proposed for managing DH that demineralized dentin with exposed DTs is rubbed with ultrahighly concentrated polyelectrolyte-calcium suspension (4g L-1 -5.44m) followed by phosphate solution (3.25m), each 10min, leading to heavy remineralization of demineralized dentin and compact occlusion of the DTs over 200µm after 1 day of in vitro and in vivo incubation. For the first time, it is demonstrated that the PCCP process relies on the pH-dependent electrostatic attraction between electropositive polyelectrolyte-calcium complexes and electronegative inwalls of DTs comprised of collagen fibrils and hydroxyapatite crystals under alkaline condition. The PCCP process might shed light on a promising dentin desensitizing strategy for DH management via rapid in-depth DT occlusion and remineralization of demineralized dentin.

Gluteus Maximus Calcific Tendinitis.

Calcific tendinitis is seen in about 3 % of people and affects slightly more women. It is usually seen between the ages of 40 and 70. Calcium deposition is most common in the shoulders, but can also occur in the hips, elbows, wrists, and knees. Although calcific tendinitis is mostly asymptomatic, it can sometimes be characterized by brief bouts of acute pain accompanied by erythema, edema, and even fever. A self-limiting disorder caused by the calcium hydroxyapatite depositing within tendons, often those of the rotator cuff, is calcific tendinitis, also known as calcific tendinopathy or tendonitis. It is a frequent hydroxyapatite crystal deposition disease presentation (HADD). (Malghem, et al., 2015 Skeletal radiology 44 (10): 1403–1412).

Bioceramics/Electrospun Polymeric Nanofibrous and Carbon Nanofibrous Scaffolds for Bone Tissue Engineering Applications.

Bone tissue engineering integrates biomaterials, cells, and bioactive agents to propose sophisticated treatment options over conventional choices. Scaffolds have central roles in this scenario, and precisely designed and fabricated structures with the highest similarity to bone tissue have shown promising outcomes. On the other hand, using nanotechnology and nanomaterials as the enabling options confers fascinating properties to the scaffolds, such as precisely tailoring the physicochemical features and better interactions with cells and surrounding tissues. Among different nanomaterials, polymeric nanofibers and carbon nanofibers have attracted significant attention due to their similarity to bone extracellular matrix (ECM) and high surface-to-volume ratio. Moreover, bone ECM is a biocomposite of collagen fibers and hydroxyapatite crystals; accordingly, researchers have tried to mimic this biocomposite using the mineralization of various polymeric and carbon nanofibers and have shown that the mineralized nanofibers are promising structures to augment the bone healing process in the tissue engineering scenario. In this paper, we reviewed the bone structure, bone defects/fracture healing process, and various structures/cells/growth factors applicable to bone tissue engineering applications. Then, we highlighted the mineralized polymeric and carbon nanofibers and their fabrication methods.

Lignin-enriched tricalcium phosphate/sodium alginate 3D scaffolds for application in bone tissue regeneration

The bone is a connective, vascularized, and mineralized tissue that confers protection to organs, and participates in the support and locomotion of the human body, maintenance of homeostasis, as well as in hematopoiesis. However, throughout the lifetime, bone defects may arise due to traumas (mechanical fractures), diseases, and/or aging, which when too extensive compromise the ability of the bone to self-regenerate. To surpass such clinical situation, different therapeutic approaches have been pursued. Rapid prototyping techniques using composite materials (consisting of ceramics and polymers) have been used to produce customized 3D structures with osteoinductive and osteoconductive properties. In order to reinforce the mechanical and osteogenic properties of these 3D structures, herein, a new 3D scaffold was produced through the layer-by-layer deposition of a tricalcium phosphate (TCP), sodium alginate (SA), and lignin (LG) mixture using the Fab@Home 3D-Plotter. Three different TCP/LG/SA formulations, LG/SA ratio 1:3, 1:2, or 1:1, were produced and subsequently evaluated to determine their suitability for bone regeneration. The physicochemical assays demonstrated that the LG inclusion improved the mechanical resistance of the scaffolds, particularly in the 1:2 ratio, since a 15 % increase in the mechanical strength was observed. Moreover, all TCP/LG/SA formulations showed an enhanced wettability and maintained their capacity to promote the osteoblasts' adhesion and proliferation as well as their bioactivity (formation of hydroxyapatite crystals). Such results support the LG inclusion and application in the development of 3D scaffolds aimed for bone regeneration.

All that illuminates on radionuclide imaging is not a metastatic lesion: Role of complementary imaging

Radionuclide imaging is a non-invasive modality based on tracer physiology widely utilized in the diagnosis, staging, therapeutic evaluation, and monitoring of metastatic disease in a spectrum of malignancies. Calcific tendinopathy is a well-recognized disorder related to the deposition of calcium hydroxyapatite crystals within tendons. We describe a patient with urothelial carcinoma of the bladder revealing increased uptake at the left hip on 99mTc labeled methylene diphosphonate scintigraphy suggesting a metastatic lesion. Cross-sectional imaging with magnetic resonance imaging confirmed the accurate diagnosis of calcific tendinopathy of gluteus maximus insertion. This case report highlights the importance of a thorough clinical evaluation and complementary imaging in assessing benign pathologies which may mimic metastatic bone lesions.

Triple-gene deletion for osteocalcin significantly impairs the alignment of hydroxyapatite crystals and collagen in mice.

Osteocalcin (Ocn), also known as bone Gla protein, is synthesized by osteoblasts and thought to regulate energy metabolism, testosterone synthesis and brain development. However, its function in bone is not fully understood. Mice have three Ocn genes: Bglap, Bglap2 and Bglap3. Due to the long span of these genes in the mouse genome and the low expression of Bglap3 in bone, researchers commonly use Bglap and Bglap2 knockout mice to investigate the function of Ocn. However, it is unclear whether Bglap3 has any compensatory mechanisms when Bglap and Bglap2 are knocked out. Considering the controversy surrounding the role of Ocn in bone, we constructed an Ocn-deficient mouse model by knocking out all three genes (Ocn-/-) and analyzed bone quality by Raman spectroscopy (RS), Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and MicroCT (μCT). The RS test showed that the alignment of hydroxyapatite crystals and collagen fibers was significantly poorer in Ocn-/- mice than in wild-type (WT) mice. Ocn deficiency resulted in a looser surface structure of bone particles and a larger gap area proportion. FTIR analysis showed few differences in bone mineral index between WT and Ocn-/- mice, while μCT analysis showed no significant difference in cortical and trabecular regions. However, under tail-suspension simulating bone loss condition, the disorder of hydroxyapatite and collagen fiber alignment in Ocn-/- mice led to more obvious changes in bone mineral composition. Collectively, our results revealed that Ocn is necessary for regulating the alignment of minerals parallel to collagen fibrils.

A Tunable Calcium Phosphate Coating to Drive in vivo Osseointegration of Composite Engineered Tissues

Varying degrees of hydroxyapatite (HA) surface functionalization have been implicated as the primary driver of differential osteogenesis observed in infiltrating cells. The ability to reliably create spatially controlled areas of mineralization in composite engineered tissues is of growing interest in the field, and the use of HA-functionalized biomaterials may provide a robust solution to this challenge. In this study, we successfully fabricated polycaprolactone salt-leached scaffolds with two levels of a biomimetic calcium phosphate coating to examine their effects on MSC osteogenesis. Longer duration coating in simulated body fluid (SBF) led to increased HA crystal nucleation within scaffold interiors as well as more robust HA crystal formation on scaffold surfaces. Ultimately, the increased surface stiffness of scaffolds coated in SBF for 7 days in comparison to scaffolds coated in SBF for 1 day led to more robust osteogenesis of MSCs in vitro without the assistance of osteogenic signaling molecules. This study also demonstrated that the use of SBF-based HA coatings can promote higher levels of osteogenesis in vivo. Finally, when incorporated as the endplate region of a larger tissue-engineered intervertebral disc replacement, HA coating did not induce mineralization in or promote cell migration out of neighboring biomaterials. Overall, these results verified tunable biomimetic HA coatings as a promising biomaterial modification to promote discrete regions of mineralization within composite engineered tissues.

Formulation and evaluation of alginate-gelatin hydrogel scaffolds loaded with zinc-doped hydroxyapatite and 5-fluorouracil

Alginate and gelatin are natural macromolecules used to formulate biocompatible drug delivery systems. Hydroxyapatite (HA) is an osteophilic ceramic used to prepare bone scaffolds. The current study aimed at preparing and characterizing HA, zinc-doped HA, and 5-fluorouracil(5-FU)-loaded alginate-gelatin-based hydrogel scaffolds using different crosslinking solutions. 5-FU incorporation efficiency, in-vitro drug release, antitumor bioassays, FTIR, X-ray-diffraction (XRD), High-Resolution Transmission, and Scanning-Electron Microscope (HR-TEM and SEM) studies were conducted. XRD showed the incorporation of Zn2+ into HA structure with a deformity in HA crystal lattice and inhibited crystal growth. FTIR-spectra represented the characteristic bands corresponding to HA structure. HR-TEM showed a decreased HA crystal size and rod-like crystallites that increased with increasing zinc content. Zn2+ content and 5-FU-loading caused significant effects on the scaffolds' thickness (p-value = 0.021 and 0.035, respectively). Burst 5-FU release within 10–15 min followed by 100 % release within 4 h was observed. Zinc content showed a significant positive effect on the cytotoxicity% of the blank and drug-loaded scaffolds. XRD and FTIR studies revealed that 5-FU was completely incorporated into the hydrogel with no chemical interaction. SEM-imaging showed interconnected pores and needle-shaped drug particles. The prepared formulations showed promising physico-chemical properties for targeted delivery of 5-FU in the form of biocompatible bone scaffolds.

Mussel-Inspired Caries Management Strategy: Constructing a Tribioactive Tooth Surface with Remineralization, Antibiofilm, and Anti-inflammation Activity.

Dental caries is a common chronic oral disease in humans resulting from tooth demineralization caused by acid production of bacterial plaque, which leads to the destruction of enamel and dentin and oral inflammation. However, it is still a challenge that the function of natural active ingredients in currently available oral care products is not comprehensive, especially the lack of remineralization. Here, inspired by the strong biological adhesion ability of mussels and ancient oral disease plant therapy, a multifunctional strategy is proposed to construct a bioactive tooth surface to treat dental caries. It has been demonstrated that the Turkish gall extract (TGE) can inhibit adhesion of cariogenic bacteria Streptococcus mutans and Actinomyces viscosus and destroy biofilms on the tooth surface. Meanwhile, TGE can reduce the expression of inflammatory factors. Notably, the TGE coating can induce the growth of hydroxyapatite (HAP) crystals in vivo and in vitro, recovering the enamel mechanical properties under normal oral conditions. MD simulations interpreted the adsorption mechanism by which the hydroxyl groups in TGE bind to phosphate group (PO43-) on the tooth surface, attracting calcium ions (Ca2+) as nucleation sites for remineralization. This work underlines the importance of TGE coating in remineralization, antibiofilm, and anti-inflammation activity as a promising strategy for dental caries.

Strontium hydroxyapatite/magnesium oxychloride cement with high strength and high osteogenic activity for bone defect repair

Strontium is a kind of element which can promote the increase of bone density and benefit the growth of bone tissue. This study combined strontium hydroxyapatite (Sr-HAp) with magnesium oxychloride cement (MOC) to prepare a bioactive material with good osteogenic activity and degradability. The results revealed that the incorporation of 10 wt.% Sr-HAp densified the structure of MOC, slowed down the degradation rate of hydration product phase 5 in water, and enhanced the water resistance of MOC. After soaking for 28 days, the compressive strength of Sr-HAp/MOC decreased by 53%, which was lower than that of MOC (93%) and HAp/MOC (61%) without adding Sr-HAp. During the degradation process in vitro, Sr-HAp/MOC continuously released Sr2+ and the cumulative concentration of Sr2+ released in vitro after seven days of immersion was 1.27 ± 0.15 ppm. When Sr-HAp/MOC was soaking in simulated body fluid, Sr-HAp induced the growth and deposition of bone-like component hydroxyapatite crystals on MOC’s surface, improving MOC’s bioactivity. After implantation of femur defect in rats, the new bone tissue grew from outside to inside around Sr-HAp/MOC, which showed Sr-HAp/MOC had better osteogenic activity. MOC was containing 10 wt.% Sr-HAp can not only provide strong support for bone defects but also have the potential to promote bone regeneration.

Autologous Tooth Graft: Innovative Biomaterial for Bone Regeneration. Tooth Transformer® and the Role of Microbiota in Regenerative Dentistry. A Systematic Review.

Different biomaterials, from synthetic products to autologous or heterologous grafts, have been suggested for the preservation and regeneration of bone. The aim of this study is to evaluate the effectiveness of autologous tooth as a grafting material and examine the properties of this material and its interactions with bone metabolism. PubMed, Scopus, Cochrane Library, and Web of Science were searched to find articles addressing our topic published from 1 January 2012 up to 22 November 2022, and a total of 1516 studies were identified. Eighteen papers in all were considered in this review for qualitative analysis. Demineralized dentin can be used as a graft material, since it shows high cell compatibility and promotes rapid bone regeneration by striking an ideal balance between bone resorption and production; it also has several benefits, such as quick recovery times, high-quality newly formed bone, low costs, no risk of disease transmission, the ability to be performed as an outpatient procedure, and no donor-related postoperative complications. Demineralization is a crucial step in the tooth treatment process, which includes cleaning, grinding, and demineralization. Since the presence of hydroxyapatite crystals prevents the release of growth factors, demineralization is essential for effective regenerative surgery. Even though the relationship between the bone system and dysbiosis has not yet been fully explored, this study highlights an association between bone and gut microbes. The creation of additional scientific studies to build upon and enhance the findings of this study should be a future objective of scientific research.

Biological properties of hydroxyapatite coatings on titanium dioxide nanotube surfaces using negative pressure method.

Titanium (Ti) exhibits superior biocompatibility and mechanical properties but is bioinert, while hydroxyapatite (HA) possesses excellent osteogenesis and is widely used for the modification of Ti surface coatings. However, the synthesis of homogeneous and stable HA on metallic materials is still a major challenge. In this study, porous titanium dioxide nanotube arrays were prepared on Ti surface by anodic oxidation, loaded with calcium and phosphorus precursors by negative pressure immersion, and HA coating was formed by in situ crystallization of calcium and phosphorus on the surface by hydrothermal heating. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and bonding strength were conducted to confirm the surface characteristics of each group. The cell proliferation, mineralization degree, and alkaline phosphatase (ALP) activity of MC3T3-E1 cells on samples were calculated and compared in vitro experiments. Cylindrical samples were implanted into rat femurs to evaluate biocompatibility and osteogenesis in vivo. The results showed that HA crystals successfully synthesized in TiO2 nanotubes, enhancing the bonding strength of HA coating and Ti substrate under negative pressure. Moreover, HA coating on Ti substrate remarkably enhanced cell proliferation and osteogenic differentiation activity in vitro, and improved new bone formation as well as osseointegration in vivo.

Bioactive Materials for Caries Management: A Literature Review.

Researchers have developed novel bioactive materials for caries management. Many clinicians also favour these materials, which fit their contemporary practice philosophy of using the medical model of caries management and minimally invasive dentistry. Although there is no consensus on the definition of bioactive materials, bioactive materials in cariology are generally considered to be those that can form hydroxyapatite crystals on the tooth surface. Common bioactive materials include fluoride-based materials, calcium- and phosphate-based materials, graphene-based materials, metal and metal-oxide nanomaterials and peptide-based materials. Silver diamine fluoride (SDF) is a fluoride-based material containing silver; silver is antibacterial and fluoride promotes remineralisation. Casein phosphopeptide-amorphous calcium phosphate is a calcium- and phosphate-based material that can be added to toothpaste and chewing gum for caries prevention. Researchers use graphene-based materials and metal or metal-oxide nanomaterials as anticaries agents. Graphene-based materials, such as graphene oxide-silver, have antibacterial and mineralising properties. Metal and metal-oxide nanomaterials, such as silver and copper oxide, are antimicrobial. Incorporating mineralising materials could introduce remineralising properties to metallic nanoparticles. Researchers have also developed antimicrobial peptides with mineralising properties for caries prevention. The purpose of this literature review is to provide an overview of current bioactive materials for caries management.

Role of galectin-3 in vascular calcification.

Vascular calcification is an abnormal process in which bone specific hydroxyapatite crystals are actively deposited on the vascular wall mediated by phenotypic differentiated smooth muscle cells and other mesenchymal cells under various pathological conditions. It is one of the important characteristics in the occurrence and development of atherosclerosis, prevalent in patients with type 2 diabetes and advanced chronic kidney disease, especially those requiring maintenance hemodialysis, with severely threatening human health. Previous studies have shown that the early diagnosis and control of vascular calcification is of great significance for cardiovascular risk stratification, prevention of acute cardiovascular events, which can greatly improve the prognosis and quality of life of patients. Galectins are a family of lectin superfamily. It is widely distributed in various animals and plays an important role in many physiological and pathological processes, such as cell adhesion, apoptosis, inflammatory response, tumor metastasis and so on. Many biomarker-and association-related studies and Preclinical-mechanistic studies have suggested that galactose-specific lectin-3 (galectin-3) plays an important role in vascular calcification and vascular intimal calcification (VIC) calcification induced by Wnt/βcatenin signaling pathway, NF-κB signaling pathway and ERK1/2 signaling pathway. This paper mainly expounds the role and mechanism of galectin-3 in vascular calcification under different pathological conditions including atherosclerosis, diabetes and chronic kidney disease.