Nucleotide pyrophosphatase phosphodiesterase 1 (NPP1) is required for the conversion of extracellular ATP into inorganic pyrophosphate (PP.sub.i ), a recognised inhibitor of hydroxyapatite (HA) ...crystal formation. A detailed phenotypic assessment of a mouse model lacking NPP1 (Enpp1.sup.-/-) was completed to determine the role of NPP1 in skeletal and soft tissue mineralization in juvenile and adult mice. Histopathological assessment of Enpp1.sup.-/- mice at 22 weeks of age revealed calcification in the aorta and kidney and ectopic cartilage formation in the joints and spine. Radiographic assessment of the hind-limb showed hyper-mineralization in the talocrural joint and hypo-mineralization in the femur and tibia. MicroCT analysis of the tibia and femur disclosed altered trabecular architecture and bone geometry at 6 and 22 weeks of age in Enpp1.sup.-/- mice. Trabecular number, trabecular bone volume, structure model index, trabecular and cortical thickness were all significantly reduced in tibiae and femurs from Enpp1.sup.-/- mice (P0.05). Bone stiffness as determined by 3-point bending was significantly reduced in Enpp1.sup.-/- tibiae and femurs from 22-week-old mice (P0.05). Circulating phosphate and calcium levels were reduced (P0.05) in the Enpp1.sup.-/- null mice. Plasma levels of osteocalcin were significantly decreased at 6 weeks of age (P0.05) in Enpp1.sup.-/- mice, with no differences noted at 22 weeks of age. Plasma levels of CTx (RatlapsTM) and the phosphaturic hormone FGF-23 were significantly increased in the Enpp1.sup.-/- mice at 22 weeks of age (P0.05). Fgf-23 messenger RNA expression in cavarial osteoblasts was increased 12-fold in Enpp1.sup.-/- mice compared to controls. These results indicate that Enpp1.sup.-/- mice are characterized by severe disruption to the architecture and mineralization of long-bones, dysregulation of calcium/phosphate homeostasis and changes in Fgf-23 expression. We conclude that NPP1 is essential for normal bone development and control of physiological bone mineralization.
Multiscale engineered artificial tooth enamel Zhao, Hewei; Liu, Shaojia; Wei, Yan ...
Science (American Association for the Advancement of Science),
02/2022, Volume:
375, Issue:
6580
Journal Article
Peer reviewed
Tooth enamel, renowned for its high stiffness, hardness, and viscoelasticity, is an ideal model for designing biomimetic materials, but accurate replication of complex hierarchical organization of ...high-performance biomaterials in scalable abiological composites is challenging. We engineered an enamel analog with the essential hierarchical structure at multiple scales through assembly of amorphous intergranular phase (AIP)-coated hydroxyapatite nanowires intertwined with polyvinyl alcohol. The nanocomposite simultaneously exhibited high stiffness, hardness, strength, viscoelasticity, and toughness, exceeding the properties of enamel and previously manufactured bulk enamel-inspired materials. The presence of AIP, polymer confinement, and strong interfacial adhesion are all needed for high mechanical performance. This multiscale design is suitable for scalable production of high-performance materials.
Nano-hydroxyapatite (nano-HA) is a material with multiple uses due to its biocompatibility and its resemblance to the nonorganic bone structure. It is used in various dental domains such as ...implantology, surgery, periodontology, esthetics and prevention. The aim of this study is to provide a wide understanding of nano-HA and to promote treatments based on nanomaterials in dentistry. A search in two data bases, Scopus, and PubMED, was conducted over a 5 years period. We chose a 5 years period because this revealed the most recent published studies with the key words 'nano-HA' and 'dentistry'. A number of 32 studies were included in this systematic review. In implantology the main use of nano-HA was as a coating material for titanium implants and its effect was assessed in the matter of osteointegration and inflammatory response as well as antibacterial activity. In tissue engineering the use of nano-HA was directed to surgery and periodontology and this material was assessed mainly as a grafting material. In esthetics and prevention its use was mainly focused on dentinal hypersensitivity treatment, remineralizing potential and as bleaching co-agent. Nano-HA is a relatively novel material with outstanding physical, chemical, mechanical and biological properties that makes it suitable for multiple interventions. It outperformed most of the classic materials used in implantology and surgery but it should be further investigated for bone engineering and caries prevention therapy.
•Spherical and rod-shaped HAp successfully reduced peroxide permeability.•Both morphologies reduced dental demineralization.•Prior application of HAp did not reduce bleaching efficacy.
This study ...aims to synthesize, characterize, and assess the penetration of hydrogen peroxide (HP), color change (CC), and surface morphology changes after the application of two distinct nano-hydroxyapatite (nano-HAp).
Two nano-HAp were previously synthesized by co-precipitation: one with rod-shaped particles (RS) and the other with spherical-shaped particles (SS). The surface charge of the nano-HAp particles was determined at varying pH levels and characterized by X-ray diffraction patterns and Fourier transform infrared spectroscopy. The morphology of the samples was assessed using scanning electron microscopy (SEM). The nano-HAp particles were applied before the dental bleaching procedure. Forty teeth were divided into four groups (n = 10) according to the bleaching treatment: no treatment, bleaching with 35% HP only, RS application and bleaching with 35% HP, and SS application and bleaching with 35% HP. HP concentration (µg mL−1) was measured using UV-Vis, while CC was evaluated with a digital spectrophotometer (ΔEab, ΔE00 and WID). Additionally, four teeth from each group were selected for SEM analysis. Statistical analysis encompassed one-way ANOVA, Tukey's, and Dunnet's tests.
RS and SS were successfully synthesized by coprecipitation, primarily differing in pH during synthesis. Both variations of nano-HAp morphology significantly reduced HP diffusion into the pulp chamber (p < 0.001). Regarding enamel morphology, groups analyzed post dental bleaching exhibited greater HAp deposition on the enamel surface. Notably, this deposition did not impede CC.
The utilization of different nano-HAp morphologies prior to dental bleaching appears to be a promising strategy for mitigating adverse effects associated with dental bleaching procedures.
The aim of the study was to assess the efficacy of three methods of enamel remineralization on initial approximal caries: (1) a nano-hydroxyapatite gel, (2) gaseous ozone therapy, (3) combination of ...a nano-hydroxyapatite gel and ozone. Patients (n = 92, age 20-30 years) with initial approximal enamel lesions on premolar and molar teeth (n = 546) were randomly allocated to three groups subjected to a 6-months treatment: Group I: domestic nano-hydroxyapatite remineralizing gel, group II: in-office ozone therapy, group III: both domestic remineralizing gel and ozone therapy. Caries lesions were assessed on bitewing radiographs at baseline, after 1 year and after 2 years. At one-year follow-up, the smallest rate of lesions with remineralisation (36.5%) was found in group I, and the highest (69.3%)-in group III. In group III a significant remineralisation was noticed in after 1 year and then a demineralisation after 2 years. Thus nano-hydroxyapatite gel and ozone therapy exert some capacities to remineralize approximal enamel and dentine subsurface lesions of premolar and molar teeth. Moreover, the combination of both methods produces the best effect compared to nano-hydroxyapatite or ozone therapy applied alone. However, the treatment should be continued for a long time in order to achieve nonrestorative recovery of caries.
Purpose: The aim of research is to fabricate nanostructured hydroxyapatite (HA) coatings on the titanium via electrochemical deposition (ED). Additionally, the biological properties of the ...ED-produced HA (EDHA) coatings with a plate-like nanostructure were evaluated in vitro and in vivo by undertaking comparisons with those prepared by acid/alkali (AA) treatment and by plasma spray-produced HA (PSHA) nanotopography-free coatings. Materials and Methods: Nanoplate-like HA coatings were prepared through ED, and nanotopography-free PSHA coatings were fabricated. The surface morphology, phase composition, roughness, and wettability of these samples were investigated. Furthermore, the growth, proliferation, and osteogenic differentiation of MC3T3-E1 cells cultured on each sample were evaluated via in vitro experiments. Histological assessment and push-out tests for the bone-implant interface were performed to explore the effect of the EDHA coatings on the interfacial osseointegration in vivo. Results: XRD analysis showed that the strongest intensity for the EDHA coatings was at the (002) plane rather than at the regular (211) plane. Relatively higher surface roughness and greater wettability were observed for the EDHA coatings. Cellular experiments revealed that the plate-like nanostructured EDHA coatings not only possessed an ability, similar to that of PSHA coatings, to promote the adhesion and proliferation of MC3T3-E1 cells but also demonstrated significantly enhanced early or intermediate markers of osteogenic differentiation. Significant osseointegration enhancement in the early stage of implantation period and great bonding strength were observed at the interface of bone and EDHA samples. In comparison, relatively weak osseointegration and bonding strength of the bone-implant interface were observed for the AA treatment. Conclusion: The biological performance of the plate-like nanostructured EDHA coating, which was comparable with that of the PSHA, improves early-stage osteogenic differentiation and osseointegration abilities and has great potential for enhancing the initial stability and long-term survival of uncemented or 3D porous titanium implants. Keywords: electrochemical deposition, hydroxyapatite coatings, nanoscale, osteogenic activity, osseointegration
Hydroxyapatite (HA) is a biomaterial widely used in clinical applications and pharmaceuticals. The literature on HA-based materials studies is focused on chemical characterization and ...biocompatibility. Generally, biocompatibility is analyzed through adhesion, proliferation, and differentiation assays. Fewer studies are looking for genotoxic events. Thus, although HA-based biomaterials are widely used as biomedical devices, there is a lack of literature regarding their genotoxicity. This systematic review was carried out following the PRISMA statement. Specific search strategies were developed and performed in four electronic databases (PubMed, Science Direct, Scopus, and Web of Science). The search used “Hydroxyapatite OR Calcium Hydroxyapatite OR durapatite AND genotoxicity OR genotoxic OR DNA damage” and “Hydroxyapatite OR Calcium Hydroxyapatite OR durapatite AND mutagenicity OR mutagenic OR DNA damage” as keywords and articles published from 2000 to 2022, after removing duplicate studies and apply include and exclusion criteria, 53 articles were identified and submitted to a qualitative descriptive analysis. Most of the assays were in vitro and most of the studies did not show genotoxicity. In fact, a protective effect was observed for hydroxyapatites. Only 20 out of 71 tests performed were positive for genotoxicity. However, no point mutation-related mutagenicity was observed. As the genotoxicity of HA-based biomaterials observed was correlated with its nanostructured forms as needles or rods, it is important to follow their effect in chronic exposure to guarantee safe usage in humans.
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•Systematic evaluation of the genotoxicity of HA-based biomaterials over the past 20 years.•The genotoxic effects of HA-based biomaterials on human health are understudied.•Both in vitro and in vivo models assessed HA biomaterials' genotoxicity.•Needle-shaped HA nanoparticles appear to cause more DNA damage and chromosomal changes than the other HA shapes.•Primary cells seem to be more sensitive than cell cultures for assessing genotoxicity.
Systematic investigation of optimal conditions for preparation and in vitro stability of HAP particles labeled with .sup.223Ra, that could be considered as promising candidates for targeted ...alpha-therapy, has been carried out. Two different approaches to HAP labelling were tested: sorption of Ra.sup.2+ on pre-synthesized HAP-particles and incorporation of Ra.sup.2+ into the structure of HAP during its synthesis. Two textural forms of HAP particles were used-nanoparticles and particles with the diameter of 350 ± 20 mum. Kinetics of .sup.223Ra sorption on HAP of different particle size and desorption in 0.9 % NaCl solution were studied. The influence of solution acidity and solid to liquid phase ratio on sorption of Ra was evaluated and the sorption yield up to 98 % was achieved. It was found that the optimal conditions for the sorption included synthesis of HAP nanoparticles in the presence of .sup.223Ra at pH values of 4-7 followed by annealing at 900 °C. In this case subsequent cumulative desorption of Ra was <5 % of initial activity.
Reconstruction of osteoporotic bone defects is a clinical problem that continues to inspire the design of new materials.
: In this work, bioceramics composed of strontium (Sr)-doped hydroxyapatite ...(HA) whiskers or pure HA whiskers were successfully fabricated by hydrothermal treatment and respectively named SrWCP and WCP. Both bioceramics had similar three-dimensional (3D) porous structures and mechanical strengths, but the SrWCP bioceramic was capable of releasing Sr under physiological conditions. In an osteoporotic rat metaphyseal femoral bone defect model, both bioceramic scaffolds were implanted, and another group that received WCP plus strontium ranelate drug administration (Sr-Ran+WCP) was studied for comparison.
: At week 1 post-implantation, osteogenesis coupled blood vessels were found to be more common in the SrWCP and Sr-Ran+WCP groups, with substantial vascular-like structures. After 12 weeks of implantation, comparable to the Sr-Ran+WCP group, the SrWCP group showed induction of more new bone formation within the defect as well as at the implant-bone gap region than that of the WCP group. Both the SrWCP and Sr-Ran+WCP groups yielded a beneficial effect on the surrounding trabecular bone microstructure to resist osteoporosis-induced progressive bone loss. While an abnormally high blood Sr ion concentration was found in the Sr-Ran+WCP group, SrWCP showed little adverse effect.
: Our results collectively suggest that the SrWCP bioceramic can be a safe bone substitute for the treatment of osteoporotic bone defects, as it promotes local bone regeneration and implant osseointegration to a level that strontium ranelate can achieve.
Adequate bone regeneration has been difficult to achieve at segmental bone defects caused by disease. The surface structure and phase composition of calcium phosphate bioceramic are crucial for its ...bioactivity and osteoinductivity. In the present study, biphasic calcium phosphate (BCP) bioceramics composed of micro-whiskers and nanoparticles hybrid-structured surface (hBCP) were fabricated via a hydrothermal reaction. The in vivo long bone defect model of beagle dogs implanted with hBCP bioceramics achieved a higher quality regenerated bone as compared to the traditional smooth-surface BCP control group. After a 12-week implantation period, more new bone formation within the implanted material and a higher fracture load were observed in the hBCP group (p < 0.05 vs. control). In addition, the local bone integration efficacy, as determined by nanoindentation, showed a significantly closer elastic modulus of the implanted hBCP bioceramics to that of the natural bone adjacent. Finally, in vitro gene microarray analysis of the mesenchymal stem cells (MSCs) co-cultured with two bioceramics showed that the hBCP group induced a drastic downregulation of the genes associated with inflammatory response, which was never documented in previous studies regarding biomaterials with a micro/nano hybrid structure. The tumor necrosis factor (TNF) signalling pathway was the most involved and preferentially inhibited by the hBCP material. Collectively, the findings suggested that the micro/nano hybrid-structured bioceramics augmented local bone regeneration at segmental bone defects and presented a potential alternative to autologous bone grafts.