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Numerous remineralizing coatings aim to prevent or treat early enamel lesions and occlude exposed dentinal tubules (DTs). Nevertheless, the pace of remineralization is inadequate, and the mechanical robustness of the newly established mineral layer fails to match the inherent strength. In this study, a biomimetic mineralization strategy aimed at replicating key events in biological mineralization, specifically focusing on the organic–inorganic composite matrix, is proposed. The material utilizes Tris(2‐carboxyethyl)phosphine (TCEP), which serves a dual role: stabilized amorphous calcium phosphate (ACP) (ACP@TCEP) nanoparticles as its inorganic component, and catalyzing the cleavage of intramolecular disulfide bonds in poly(ethylene glycol) (PEG) grafted lysozyme (lyso‐PEG) to facilitate the formation of an amyloid‐like protein matrix composite with ACP (ACP@lyso‐PEG nanocomplexes). ACP@lyso‐PEG nanocomplexes can rapidly and efficiently form an enamel‐like remineralization layer on the surface of damaged dental hard tissue, reaching ≈4.205 µm thickness after 3 days of acid‐etched enamel. Furthermore, achieving a depth of DTs occlusion exceeding 60 µm after 5 days, using a simple immersion process. The resulting mineralized layer exhibits mechanical strength comparable to natural teeth. This study introduces a conceptual biomimetic mineralization strategy for effective enamel repair or DTs occlusion in clinical practices, and offers potential insights into the mechanisms of biomineral formation. [ABSTRACT FROM AUTHOR]

The cell (plasma) membrane is enriched with numerous receptors, ligands, enzymes, and phospholipids that play important roles in cell-cell and cell-extracellular matrix interactions governing, for instance, tissue development and repair. We previously showed that plasma membrane nanofragments (PMNFs) act as nucleation sites for bone formation in vivo , and induce in vitro mineralization within 1 day. In this study, we optimized the methods for generating, isolating, and applying PMNFs as a cell-free therapeutic to expedite bone defect repair. The PMNFs were isolated from different mouse cell lines (chondrocytes, osteoblasts, and fibroblasts), pre-conditioned, lyophilized, and subsequently transplanted into 2 mm critical-sized calvarial defects in mice (n = 75). The PMNFs from chondrocytes, following a 3-day pre-incubation, significantly accelerated bone repair within 2 weeks, through a coordinated attraction of macrophages, endothelial cells, and osteoblasts to the healing site. In vitro experiments confirmed that PMNFs enhanced cell adhesion. Comparison of the PMNF efficacy with phosphatidylserine, amorphous calcium phosphate (ACP), and living cells confirmed the unique ability of PMNFs to promote accelerated bone repair. Importantly, PMNFs promoted nearly complete integration of the regenerated bone with native tissue after 6 weeks (% non-integrated bone area = 15.02), contrasting with the partial integration (% non-integrated bone area = 56.10; p < 0.01, Student's test) with transplantation of ACP. Vickers microhardness tests demonstrated that the regenerated bone after 6 weeks (30.10 ± 1.75) exhibited hardness similar to native bone (31.07 ± 2.46). In conclusion, this is the first study to demonstrate that cell membrane can be a promising cell-free material with multifaceted biofunctional properties that promote accelerated bone repair. • For the first time, the cell (plasma) membrane is used as material for bone repair. • The plasma membrane from chondrocytes promoted rapid bone repair within 2 weeks, with complete integration of the newly formed bone with the surrounding native tissue. • The plasma membrane from chondrocytes presented multifaceted effects, strongly promoting the attraction of macrophages, endothelial cells and osteoblasts to the healing site. [Display omitted] [ABSTRACT FROM AUTHOR]

Energy metabolism disorders leading to tissue destruction are major causes of osteoporosis. While efficacious, bone repair strategies that modulate energy metabolism pose considerable challenges. Herein, an energetic calcium phosphate nanominerals (ECPN) is developed using polyphosphate as an energy source for osteoporosis treatment. ECPN promotes adenosine triphosphate (ATP) production in the physiological environment, providing energy to attain metabolic homeostasis. It significantly enhances rBMSCs’ autophagy capacity by activating the AMPK‐related pathway, promoting osteogenic differentiation, and rebuilding the bone regeneration microenvironment. ECPN's unique nanostructure can fully mineralize collagen fibers, enhancing the bone matrix's mechanical properties. In vivo, ECPN rapidly infiltrates osteoporotic bones, fills defects, mineralizes the matrix, and promotes new‐bone formation. The repaired bone exhibits mechanical properties comparable to those of normal bones. ECPN balances the time‐sensitive need for immediate bone matrix mineralization and long‐term construction of an osteogenic microenvironment during osteoporosis treatment. The potential of this metabolic fuel for generating functional nanomaterials for tissue engineering has been underestimated in the past. The concept of an energetic nanomineral for tissue regeneration may elicit new trends in tissue engineering. [ABSTRACT FROM AUTHOR]

Dental enamel is a mineralized extracellular matrix, and enamel defect is a common oral disease. However, the self‐repair capacity of enamel is limited due to the absence of cellular components and organic matter. Efficacy of biomimetic enamel mineralization using calcium phosphate ion clusters (CPICs), is an effective method to compensate for the limited self‐healing ability of fully developed enamel. Preparing and stabilizing CPICs presents a significant challenge, as the addition of certain stabilizers can diminish the mechanical properties or biosafety of mineralized enamel. To efficiently and safely repair enamel damage, this study quickly prepared CPICs without stabilizers using the atomization method. The formed CPICs were evenly distributed on the enamel surface, prompting directional growth and transformation of hydroxyapatite (HA) crystals. The study revealed that the mended enamel displayed comparable morphology, chemical composition, hardness, and mechanical properties to those of the original enamel. The approach of repairing dental enamel by utilizing ultrasonic nebulization of CPICs is highly efficient and safe, therefore indicating great promise. [ABSTRACT FROM AUTHOR]

Objective To prepare and identify the polyacrylic acid-citrate-amorphous calcium phosphate composite (PAA-Cit-ACP), and analyze its effect on dentin remineralization. Methods PAA-Cit-ACP was prepared by co-precipitation and freeze-drying methods. The composite was characterized by FTIR, XRD, Zeta potential, SEM, TEM and SAED. SEM was used to analyze the effect of PAA-Cit-ACP on dentin remineralization. Cell cytotoxicity of PAA-Cit-ACP was evaluated by CCK-8 method. Results The characteristic peaks of carboxyl (1 567 cm-1 and 1 416 cm-1) and ACP (1 064 cm-1 and 563 cm-1) were simultaneously observed in the FTIR spectrum, and the XRD and SAED results confirmed its amorphous state. The Zeta potential of PAA-Cit-ACP was -18.47 mV. PAA-Cit-ACP appeared as spherical nanoparticles according to SEM and TEM. In SEM images, a large amount of new minerals formed on the surface of demineralized dentin after PAA-Cit-ACP treatment. The CCK-8 result showed that PAA-Cit-ACP exhibited good biocompatibility at a concentration of 250, 500, and 1 000 μg/mL. Conclusion Citrate can co-stabilize supersaturated calcium phosphate solutions with polyacrylic acid, forming polyacrylic acid citrate amorphous calcium phosphate which can promote dentin remineralization.

Abstract Dental caries is a worldwide public healthcare concern, and is closely related to the acidic environment that caused by bacterial decomposition of food. In this study, a two-step ion exchange liquid-phase stripping method was applied to strip out vermiculite (VMT) nanosheets, then amorphous calcium phosphate (ACP) and dextran were inserted between the VMT nanosheets interlayer to obtain a composite two-dimension nanosheets (VMT/ACP/Dextran). VMT/ACP/Dextran composite nanosheets exhibited excellent biocompatibility and could provide exogenous Ca2+and PO4 3− from ACP, provide SiO4 4−, Mg2+, Fe2+ and obtain buffering pH and antibacterial properties from VMT, as well as improve suspension stability and targeting Streptococcus mutans through glucan. The in vitro study showed that the composite materials could promote the mineralization and sealing of dentin tubules by releasing active ions, buffer pH 4.5 (a value close to the pH in the dental plaque environment) to pH 6.6–7.1 (values close to the pH in human saliva) through ion exchange, and exert antibacterial effects by targeting Streptococcus mutans and exerting oxidase like and peroxidase like activities to produce reactive oxygen species (ROS). The in vivo animal study showed that daily cleaning teeth using VMT/ACP/Dextran composite nanosheets could effectively reduce the incidence rate and severity of dental caries in rats. Taking together, the developed VMT/ACP/Dextran composite nanosheets, which integrated the excellent properties of VMT, ACP and dextran, can effectively prevent dental caries through a combination of factors such as buffering acids, antibacterial properties, and promoting calcification, and may be used as an active ingredient for daily oral hygiene or filling materials to prevent and treat dental caries.

Dental caries is a worldwide public healthcare concern, and is closely related to the acidic environment that caused by bacterial decomposition of food. In this study, a two-step ion exchange liquid-phase stripping method was applied to strip out vermiculite (VMT) nanosheets, then amorphous calcium phosphate (ACP) and dextran were inserted between the VMT nanosheets interlayer to obtain a composite two-dimension nanosheets (VMT/ACP/Dextran). VMT/ACP/Dextran composite nanosheets exhibited excellent biocompatibility and could provide exogenous Ca2+and PO43− from ACP, provide SiO44−, Mg2+, Fe2+ and obtain buffering pH and antibacterial properties from VMT, as well as improve suspension stability and targeting Streptococcus mutans through glucan. The in vitro study showed that the composite materials could promote the mineralization and sealing of dentin tubules by releasing active ions, buffer pH 4.5 (a value close to the pH in the dental plaque environment) to pH 6.6–7.1 (values close to the pH in human saliva) through ion exchange, and exert antibacterial effects by targeting Streptococcus mutans and exerting oxidase like and peroxidase like activities to produce reactive oxygen species (ROS). The in vivo animal study showed that daily cleaning teeth using VMT/ACP/Dextran composite nanosheets could effectively reduce the incidence rate and severity of dental caries in rats. Taking together, the developed VMT/ACP/Dextran composite nanosheets, which integrated the excellent properties of VMT, ACP and dextran, can effectively prevent dental caries through a combination of factors such as buffering acids, antibacterial properties, and promoting calcification, and may be used as an active ingredient for daily oral hygiene or filling materials to prevent and treat dental caries. [ABSTRACT FROM AUTHOR]

Objectives: This study was aimed to obtain an experimental bleaching agent by adding casein phosphopeptide‐amorphous calcium phosphate (CPP‐ACP) in order to eliminate the mineral loss on the tooth surface after bleaching and to evaluate the bleaching effectiveness. Materials and Methods: In this study, experimental bleaching agents containing 1%, 3% CPP‐ACP and without CPP‐ACP were obtained. Bleaching effectiveness (color change), the effect of bleaching agents on mineral content (energy dispersive x‐ray spectroscopy), surface morphology (scanning electron microscope), and surface hardness of enamel (Vicker's microhardness) before and after bleaching were evaluated. The obtained data were statistically analyzed. Results: When the bleaching levels of the groups were compared, no statistically significant difference was observed between the control and 1% CPP‐ACP groups (p > 0.05) while the addition of 3% CPP‐ACP decreased significantly the effectiveness of the bleaching agent (p < 0.05). When the effects of experimental bleaching agents on surface hardness were examined, while the enamel surface hardness decreased statistically significantly after application in the control group (p < 0.05), no statistically significant change was observed in surface hardness after the application of 1% CPP‐ACP containing bleaching agent (p > 0.05). However, a statistically significant increase was observed in surface hardness after the application of 3% CPP‐ACP containing bleaching agent (p < 0.05). When the Ca and P ratio of the groups were compared, no statistically significant difference was observed between the control and 1% CPP‐ACP groups (p > 0.05), while they increased significantly in 3% CPP‐ACP group (p < 0.05). Conclusions: The addition of 1% CPP‐ACP to the bleaching agent had positive effects on the mineral content and surface hardness of the enamel, and did not negatively affect the whitening effectiveness. Clinical Significance: Adding CPP‐ACP to the bleaching agent at appropriate concentrations can eliminate possible negative effects without compromising the effectiveness of the bleaching agent. [ABSTRACT FROM AUTHOR]

This review elucidates the mechanisms underpinning intrafibrillar mineralization, examines various amorphous calcium phosphate (ACP) stabilizers employed in dentin's intrafibrillar mineralization, and addresses the challenges encountered in clinical applications of ACP-based bioactive materials. The literature search for this review was conducted using three electronic databases: PubMed, Web of Science, and Google Scholar, with specific keywords. Articles were selected based on inclusion and exclusion criteria, allowing for a detailed examination and summary of current research on dentin remineralization facilitated by ACP under the influence of various types of stabilizers. This review underscores the latest advancements in the role of ACP in promoting dentin remineralization, particularly intrafibrillar mineralization, under the regulation of various stabilizers. These stabilizers predominantly comprise non-collagenous proteins, their analogs, and polymers. Despite the diversity of stabilizers, the mechanisms they employ to enhance intrafibrillar remineralization are found to be interrelated, indicating multiple driving forces behind this process. However, challenges remain in effectively designing clinically viable products using stabilized ACP and maximizing intrafibrillar mineralization with limited materials in practical applications. The role of ACP in remineralization has gained significant attention in dental research, with substantial progress made in the study of dentin biomimetic mineralization. Given ACP's instability without additives, the presence of ACP stabilizers is crucial for achieving in vitro intrafibrillar mineralization. However, there is a lack of comprehensive and exhaustive reviews on ACP bioactive materials under the regulation of stabilizers. A detailed summary of these stabilizers is also instrumental in better understanding the complex process of intrafibrillar mineralization. Compared to traditional remineralization methods, bioactive materials capable of regulating ACP stability and controlling release demonstrate immense potential in enhancing clinical treatment standards. [ABSTRACT FROM AUTHOR]

Using a titration setup to accurately control the reaction conditions and in situ monitor the reaction, we showed that fluoride exhibited negligible effects on the ion association process of calcium and phosphate and the formation of ACP nanospheres in a buffer solution with constant ionic strength. However, the stability of ACP increased with increasing fluoride concentration, which was ascribed to the inhibitory effect of fluoride on the aggregation of ACP nanospheres and the nucleation of nanocrystals on the surface of ACP nanospheres. Furthermore, fluoride could inhibit the lateral growth of HAP nanosheets and promote the formation of rod-like crystals. These results further improve our understanding of the crystallization pathway of HAP crystals and the regulatory effects of fluoride. [ABSTRACT FROM AUTHOR]

Titanium (Ti) is widely used in dental implantation. However, their lack of biological activity causes significant clinical risks associated with immediate loading and early osteointegration failure. Amorphous calcium phosphate (ACP) is reported to be a precursor of bone mineralization. Dopamine (dopa) is well known to possess strong adhesive force in natural mussels. Combining the bio‐related advantages of these materials, a dopa‐polyacrylic acid (PAA)‐ACP hybrid material on the surface of the Ti plate is judiciously fabricated. The biological adhesiveness of dopa to graft it together with PAA onto the surface of Ti is utilized. Then, the dopa‐PAA layer serves as a matrix to grow ACP species. The modified interface allows for regulations of bioactivities. MC3T3‐E1 osteoblast (MC3T3) cells indeed show improved cell proliferation and adhesion abilities on the Ti with dopa‐PAA‐ACP coatings compared to those on bare Ti or Ti with only dopa‐PAA coating. The osteogenic potential of MC3T3 cells is also considerably upregulated on dopa‐PAA‐ACP coatings. Moreover, human umbilical vein endothelial cells (HUVECs) on dopa‐PAA‐ACP coatings show higher levels of angiogenic markers. This report proves that dopa‐PAA‐ACP composite is a new and simple bioactive titanium coating to facilitate osteogenesis and angiogenesis for dental applications. [ABSTRACT FROM AUTHOR]

Despite advancements in treatment, the squamous cell carcinoma (OSCC) patient survival rate remains stagnant. Conventional therapies have limited effectiveness, necessitating novel agents. Our study aims to synthesize and characterize amorphous calcium phosphate nanoparticles (nACPs), assess their potential cytotoxic effects on premalignant and malignant OSCC cells, and investigate possible mechanisms of action. The morphological features of nACP were investigated by field emission scanning coupled with energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), and particle size distribution (PSD). Then, we examined the effect of nACPs on nanoparticle uptake, cell adhesion, viability, invasion ability, cell cycle, and gene expression. nACP uptake was dose-dependent, induced limited selectivity in cytotoxicity between healthy and malignant cells, and affected cellular adhesion and invasion. Early apoptosis was the predominant type of cell death. The nACP effect on viability was verified by alterations in the genes associated with apoptosis and proliferation. A high concentration of nACP was shown to arrest the cell cycle progression in the G0/G1 phase of both malignant and premalignant cells. This type of nACP justifies the development of a strategy for its potential use as an anti-cancer agent and/or anti-cancer active carrier for various drugs in oral cancer treatments. [ABSTRACT FROM AUTHOR]

Nanocomposite hydrogels are suitable in bone tissue engineering due to their resemblance with the extracellular matrix, ability to match complex geometries, and ability to provide a framework for cell attachment and proliferation. The nanocomposite hydrogel comprises organic and inorganic counterparts. Gelatin methacrylate (GELMA) is an extensively used organic biomaterial in tissue engineering due to its excellent biocompatibility, biodegradability, and bioactivity. The photo-crosslinking of GELMA presents a challenge when aiming to create thicker nanocomposite hydrogels due to opacity induced by fillers, which obstructs the penetration of ultraviolet (UV) light. Therefore, using a chemical crosslinking approach, we have developed nanocomposite GELMA hydrogel in this study by incorporating citrate-containing amorphous calcium phosphate (ACP_CIT). Ammonium persulfate (APS) and Tetramethylethylenediamine (TEMED) were deployed to crosslink the methacrylate group of GELMA. The oscillatory shear tests have confirmed that crosslinking enhances both storage (G′) and loss modulus (G″) of GELMA. Subsequently, incorporation of ACP_CIT in GELMA hydrogel shows further enhancement in G′ and G″ values. In vitro analysis of the developed hydrogels revealed that chemical crosslinking and incorporation of ACP_CIT do not compromise the cytocompatibility of the GELMA. Hence, for developing nanocomposite GELMA hydrogels employing APS/TEMED crosslinking emerges as a promising alternative to photo-crosslinking.

In the present work, the phase conversion of amorphous calcium phosphate (ACP) in different molten chlorides (LiCl, NaCl, KCl, CaCl 2) was investigated in detail. The main synthesis parameters influencing the phase purity and morphological features of the products include the chemical composition of molten salts, the heat treatment temperature and the ACP-to-flux ratio. The selective synthesis of single-phase Ca 5 (PO 4) 3 Cl or Ca 2 PO 4 Cl depends on the content of CaCl 2 in the reaction medium. The morphology control of Ca 5 (PO 4) 3 Cl powders was achieved by varying the KCl/CaCl 2 ratio in the flux, resulting in the formation of the particles of different size and shape. The KCl-rich fluxes led to the formation of relatively small nearly spherical particles, whereas the CaCl 2 -rich fluxes promoted an anisotropic growth of the Ca 5 (PO 4) 3 Cl crystals resulting in the formation of monodispersed hexagonally-shaped microrods. Whereas the anisotropic growth was observed at relatively low temperature (750 °C) the increase of the reaction temperature up to 1200 °C significantly reduced this effect leading to the formation of the particles with obviously low aspect ratio. The phase crystallinity and purity were analyzed using powder X-ray diffraction, FTIR spectroscopy as well as 31P, 35Cl and 1H solid-state NMR. The morphological features and chemical composition of the synthesized products were studied by SEM/EDX analysis. [ABSTRACT FROM AUTHOR]

The implantation of 3D-printed scaffolds for bone repair could be ineffective due to the early inflammatory response. In this work, porous amorphous calcium phosphate (ACP) nanospheres were employed to not only load quercetin (Que) but also mix with octacalcium phosphate (OCP) to form biphasic calcium phosphate (BCP). Afterward, the drug-loaded nanospheres (AQ) were combined with BCP and sodium alginate (SA) to fabricate the AQ-BCP/SA scaffolds with an interconnected structure for solving the anti-inflammatory challenge and thus promoting osteogenesis. The scaffolds obtained excellent mineralizing properties due to the interaction of ACP and the OCP in the component. Additionally, the stable and continuous release of Que enabled the scaffolds to synergistically induce osteogenesis and immunoregulation. The scaffolds were capable of directly promoting osteogenic differentiation in vitro by upregulating the expression of related genes Runx2, ALP, BMP2, and OCN. Meanwhile, they were also demonstrated to be beneficial in immunoregulation by inducing macrophages to transform into M2 polarization rather than M1 polarization. In vivo evaluation also confirmed the significant osteogenic and immunoregulatory effects of the scaffolds, which were helpful for ideal bone repair. Thus, the AQ-BCP/SA scaffolds have the potential to be applied in the future bone tissue engineering area. [ABSTRACT FROM AUTHOR]

This study presents a method to prepare hydrogel from Pickering emulsions stabilized with amorphous calcium phosphate (ACP). Pickering emulsion was prepared by utilizing stearic acid (Sa)-modified ACP as the emulsifier, blended oil as the dispersed phase, and aqueous sodium alginate (SA) as the continuous phase. ACP releases calcium ions to crosslink with sodium alginate when the pH decreases, forming a hydrogel. Structural characterization and surface wettability of the modified ACP were assessed through FT-IR, XRD, and contact angle measurements. Droplet sizes in the emulsion were analyzed using optical microscopy, and the release of curcumin from the hydrogel was monitored using ultraviolet spectroscopy. These results demonstrate Sa was grafted onto the surface of ACP. Stabilization of the Pickering emulsion was achieved using 4 wt% Sa-ACP. Moreover, the droplet size exhibited a reduction with heightened particle concentration, oil-water ratio, and pH. The release of curcumin was optimized at 5 wt% SA and 0.75 w/v% Sa-ACP with 53.5% release. The Ca-alginate matrices prevented the release of the curcumin at pH 1.2 and the curcumin was vastly released at pH 7.4, exhibiting pH-responsive release characteristics. These results confirmed the Sa-ACP-stabilized Pickering emulsion hydrogel could be used as an effective delivery system. [ABSTRACT FROM AUTHOR]

This article reports the successful one-step synthesis of two micron-sized composite powders consisting of chitosan and amorphous calcium phosphate. These composite materials are prepared by spray drying of a solution containing chitosan and calcium phosphate precursors. The co-precipitation of chitosan and calcium phosphate precursors during the process induces a highly homogeneous distribution of the phases. The mineral phase identified as spherical nanoparticles dispersed in chitosan showed no chemical bonding with the polymer. As demonstrated by electron microscopy, small angle X-ray scattering and spectroscopies, variation in chitosan concentrations significantly influences the size and spatial distribution of the mineral phase. These results present a promising approach for the preparation of chitosan/amorphous calcium phosphate composite powders with controlled and tunable properties with potential applications in the field of biomaterial engineering such as bone substitutes.

Abstract Titanium (Ti) is widely used in dental implantation. However, their lack of biological activity causes significant clinical risks associated with immediate loading and early osteointegration failure. Amorphous calcium phosphate (ACP) is reported to be a precursor of bone mineralization. Dopamine (dopa) is well known to possess strong adhesive force in natural mussels. Combining the bio‐related advantages of these materials, a dopa‐polyacrylic acid (PAA)‐ACP hybrid material on the surface of the Ti plate is judiciously fabricated. The biological adhesiveness of dopa to graft it together with PAA onto the surface of Ti is utilized. Then, the dopa‐PAA layer serves as a matrix to grow ACP species. The modified interface allows for regulations of bioactivities. MC3T3‐E1 osteoblast (MC3T3) cells indeed show improved cell proliferation and adhesion abilities on the Ti with dopa‐PAA‐ACP coatings compared to those on bare Ti or Ti with only dopa‐PAA coating. The osteogenic potential of MC3T3 cells is also considerably upregulated on dopa‐PAA‐ACP coatings. Moreover, human umbilical vein endothelial cells (HUVECs) on dopa‐PAA‐ACP coatings show higher levels of angiogenic markers. This report proves that dopa‐PAA‐ACP composite is a new and simple bioactive titanium coating to facilitate osteogenesis and angiogenesis for dental applications.

Acidic bacterial biofilms-associated enamel white spot lesions (WSLs) are one of the hallmarks of early caries, causing demineralization and decomposition of dental hard tissues. Therefore, to effectively prevent and treat WSLs, it is important to inhibit the activity of cariogenic bacteria while promoting the remineralization of demineralized enamel. Amorphous calcium phosphate (ACP) favors hard tissue remineralization due to its biological activity and ability to release large amounts of Ca2+ and PO43-. However, ACP-based biomineralization technology is not effective due to its lack of antimicrobial properties. Here, carboxymethyl chitosan (CMCS) was employed as a reducing agent and stabilizer, and dual-functional nanohybrids CMCS/AuNPs/ACP with biofilm resistance and mineralization properties were successfully synthesized. The addition of AuNPs enhances the antimicrobial activity and participates in regulating the formation of hydroxyapatite (HAp). The nanohybrids exhibited significant destructive effects against cariogenic bacteria and their biofilms and showed bactericidal activity under bacteria-induced acidic conditions. More importantly, this nanohybrids showed superior results in promoting the remineralization of demineralized enamel, compared to fluoride and CMCS/ACP in vitro. The CMCS/AuNPs/ACP nanohybrids not only reverse the cariogenic microenvironment at the microbial level, but also promote self-repairing of enamel WSLs regarding the microstructure. The present work offers a theoretical and experimental basis for using the CMCS/AuNPs/ACP nanohybrids as a potential dual-functional agent for the clinical treatment of enamel WSLs.

A biodegradable amorphous carbonated calcium phosphate (caCP)-incorporated polycaprolactone (PCL) composite layer was successfully deposited by a spin coater. In this specific coating, the PCL acts as a bioadhesive, since it provides a better adherence of the coatings to the substrate compared to powder coatings. The caCP–PCL coatings were deposited and formed thin layers on the surface of a Si3N4–3 wt% MWCNT (multiwalled carbon nanotube) substrate, which is an emerging type of implant material in the biomedical field. The composite coatings were examined regarding their morphology, structure and biological performance. The biocompatibility of the samples was tested in vitro with MC3T3-E1 preosteoblast cells. Owing to the caCP–PCL thin layer, the cell viability values were considerably increased compared to the substrate material. The ALP and LDH tests showed numerous living cells on the investrigated coatings. The morphology of the MC3T3-E1 cells was examined by fluorescent staining (calcein and DAPI) and scanning electron microscopy, both of which revealed a well-spread, adhered and confluent monolayer of cells. All performed biocompatibility tests were positive and indicated the applicability of the deposited thin composite layers as possible candidates for orthopaedic implants for an extended period. [ABSTRACT FROM AUTHOR]

In this work we studied the effect of adding MgO and/or Fe2O3 alone or simultaneously on in vitro bioactivity of a new sol-gel derived glass-ceramic in the system 56% SiO2 – (38 – x – y)% CaO – x% MgO – y% Fe2O3 – 6% P2O5 [(x,y) = (0,0); (6,0); (0,2); (6,2)] wt%. The in vitro bioactivity of the materials was assessed in a simulated body fluid (SBF). The materials characterization by Differential Scanning Calorimetry (DSC), BET analysis, FTIR spectroscopy, XRD analysis, ICP-OES spectroscopy and SEM-EDS, before and after soaking in SBF, showed, an absence of changes in glass transition temperature (Tg) for Mg-doped materials, whereas we recorded an increase in Tg for the material doped with Fe only. A decrease in the ionic exchange kinetic between glass-ceramics and SBF was observed for all doped materials. For the Mg-doped materials, the hydroxyapatite (HA) formation rate was delayed contrary to the Mg-free materials. The detailed interpretation of the mechanism of the effect of Fe and Mg on the bioactivity of the glass-ceramics, with consideration of other explanations given in the literature, gives more understanding of how these chemical elements affect the physicochemical properties of the doped materials. We believe, this will help to define the optimal way to tailor the behavior of such biomaterials for biomedical applications. Highlights: The glass transition temperature is not correlated to the in vitro bioactivity of the glass-ceramic. The delay effect of magnesium on hydroxyapatite formation depends on whether the magnesium is released in SBF or not. Hydroxyapatite formation rate on the glass-ceramic surface depends on the magnesium concentration in SBF. [ABSTRACT FROM AUTHOR]

A large amount of research in orthopedic and maxillofacial domains is dedicated to the development of bioactive 3D scaffolds. This includes the search for highly resorbable compounds, capable of triggering cell activity and favoring bone regeneration. Considering the phosphocalcic nature of bone mineral, these aims can be achieved by the choice of amorphous calcium phosphates (ACPs). Because of their metastable property, these compounds are however to-date seldom used in bulk form. In this work, we used a non-conventional "cold sintering" approach based on ultrafast low-pressure RT compaction to successfully consolidate ACP pellets while preserving their amorphous nature (XRD). Complementary spectroscopic analyses (FTIR, Raman, solid-state NMR) and thermal analyses showed that the starting powder underwent slight physicochemical modifications, with a partial loss of water and local change in the HPO42- ion environment. The creation of an open porous structure, which is especially adapted for non-load bearing bone defects, was also observed. Moreover, the pellets obtained exhibited sufficient mechanical resistance allowing for manipulation, surgical placement and eventual cutting/reshaping in the operation room. Three-dimensional porous scaffolds of cold-sintered reactive ACP, fabricated through this low-energy, ultrafast consolidation process, show promise toward the development of highly bioactive and tailorable biomaterials for bone regeneration, also permitting combinations with various thermosensitive drugs. [ABSTRACT FROM AUTHOR]

Soft and hard tissues possess distinct biological properties. Integrating the soft‐hard interface is difficult due to the inherent non‐osteogenesis of soft tissue, especially of anterior cruciate ligament and rotator cuff reconstruction. This property makes it difficult for tendons to be mineralized and integrated with bone in vivo. To overcome this challenge, a biomimetic mineralization strategy is employed to engineer mineralized tendons. The strategy involved infiltrating amorphous calcium phosphate precursors into collagen fibrils, resulting in hydroxyapatite deposition along the c‐axis. The mineralized tendon presented characteristics similar to bone tissue and induced osteogenic differentiation of mesenchymal stem cells. Additionally, the interface between the newly formed bone and tendon is serrated, suggesting a superb integration between the two tissues. This strategy allows for biomineralization of tendon collagen and replicating the hallmarks of the bone matrix and extracellular niche, including nanostructure and inherent osteoinductive properties, ultimately facilitating the integration of soft and hard tissues. [ABSTRACT FROM AUTHOR]

Biogenic collagen membranes (BCM) have been widely used in guided bone regeneration (GBR) owing to their biodegradability during tissue integration. However, their relatively high degradation rate and lack of pro-osteogenic properties limit their clinical outcomes. It is of great importance to endow BCM with tailored degradation as well as pro-osteogenic properties. In this study, a fluoride-modified polymer-induced liquid precursor (PILP) based biomineralization strategy was used to convert the collagen membrane from an organic phase to an apatite-based inorganic phase, thus achieving enhanced anti-degradation performance as well as osteogenesis. As a result, three phases of collagen membranes were prepared. The original BCM in the organic phase induced the mildest inflammatory response and was mostly degraded after 4 weeks. The organic-inorganic mixture phase of the collagen membrane evoked a prominent inflammatory response owing to the fluoride-containing amorphous calcium phosphate (F-ACP) nanoparticles, resulting in active angiogenesis and fibrous encapsulation, whereas the inorganic phase induced a mild inflammatory response and degraded the least owing to the transition of F-ACP particles into calcium phosphate with high crystallinity. Effective control of ACP is key to building novel apatite-based barrier membranes. The current results may pave the way for the development of advanced apatite-based membranes with enhanced barrier performances. [ABSTRACT FROM AUTHOR]

Osteochondral defect repair with a collagen/collagen-magnesium-hydroxyapatite (Col/Col-Mg-HAp) scaffold has demonstrated good clinical results. However, subchondral bone repair remained suboptimal, potentially leading to damage to the regenerated overlying neocartilage. This study aimed to improve the bone repair potential of this scaffold by incorporating newly developed strontium (Sr) ion enriched amorphous calcium phosphate (Sr-ACP) granules (100–150 μm). Sr concentration of Sr-ACP was determined with ICP-MS at 2.49 ± 0.04 wt%. Then 30 wt% ACP or Sr-ACP granules were integrated into the scaffold prototypes. The ACP or Sr-ACP granules were well embedded and distributed in the collagen matrix demonstrated by micro-CT and scanning electron microscopy/energy dispersive x-ray spectrometry. Good cytocompatibility of ACP/Sr-ACP granules and ACP/Sr-ACP enriched scaffolds was confirmed with in vitro cytotoxicity assays. An overall promising early tissue response and good biocompatibility of ACP and Sr-ACP enriched scaffolds were demonstrated in a subcutaneous mouse model. In a goat osteochondral defect model, significantly more bone was observed at 6 months with the treatment of Sr-ACP enriched scaffolds compared to scaffold-only, in particular in the weight-bearing femoral condyle subchondral bone defect. Overall, the incorporation of osteogenic Sr-ACP granules in Col/Col-Mg-HAp scaffolds showed to be a feasible and promising strategy to improve subchondral bone repair.

Amorphous calcium phosphate (ACP) which is a transient phase in natural bio-mineralization process has recently gained the spotlight. This study aimed to assess the effect of incorporation of nano-ACP (NACP) in a dental adhesive with/without surface treatment with silane coupling agent on bond strength. NACP was synthesized by the wet chemical precipitation technique. To characterize the structure of NACP, X-ray diffraction, scanning electron microscopy and energy dispersive X-ray spectroscopy were used. Forty molars were randomized into 4 groups of 10. The teeth were restored with composite resin and the bonding agent (one of the four groups). Adper Single Bond 2 was used as the control group. In 4wt% NACP group, NACP fillers were added to the bonding agent. In 0.4wt% and 4wt% SNACP groups, silanized NACP fillers were added to the bonding agent. Finally, the mode of failure of specimens was determined. Data were analyzed by one-way ANOVA and Tukey's post-hoc tests. P

Despite advancements in treatment, the squamous cell carcinoma (OSCC) patient survival rate remains stagnant. Conventional therapies have limited effectiveness, necessitating novel agents. Our study aims to synthesize and characterize amorphous calcium phosphate nanoparticles (nACPs), assess their potential cytotoxic effects on premalignant and malignant OSCC cells, and investigate possible mechanisms of action. The morphological features of nACP were investigated by field emission scanning coupled with energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), and particle size distribution (PSD). Then, we examined the effect of nACPs on nanoparticle uptake, cell adhesion, viability, invasion ability, cell cycle, and gene expression. nACP uptake was dose-dependent, induced limited selectivity in cytotoxicity between healthy and malignant cells, and affected cellular adhesion and invasion. Early apoptosis was the predominant type of cell death. The nACP effect on viability was verified by alterations in the genes associated with apoptosis and proliferation. A high concentration of nACP was shown to arrest the cell cycle progression in the G0/G1 phase of both malignant and premalignant cells. This type of nACP justifies the development of a strategy for its potential use as an anti-cancer agent and/or anti-cancer active carrier for various drugs in oral cancer treatments.

As the primary solid phase, amorphous calcium phosphate (ACP) is a pivotal precursor in cellular biomineralization. The intrinsic interplay between ACP and Howard factor underscores the significance of understanding their association for advancing biomimetic ACP development. While organic compounds play established roles in biomineralization, this study presents the synthesis of ACP with naturally occurring organic compounds (ascorbate, glutamate, and itaconate) ubiquitously found in mitochondria and vital for bone remodeling and healing. The developed ACP with organic compounds was meticulously characterized using XRD, FTIR, and solid-state 13C and 31P NMR. The morphological analysis revealed the characteristic spherical morphology with particle size close to 20 nm of all synthesized ACP variants. Notably, the type of organic compound strongly influences true density, specific surface area, particle size, and transformation. The in vitro analysis was performed with MC3T3-E1 cells, indicating the highest cell viability with ACP_ASC (ascorbate), followed by ACP_ITA (itaconate). The lowest cell viability was observed with 10 %w/v of ACP_GLU (glutamate); however, 1 %w/v of ACP_GLU was cytocompatible. Further, the effect of small organic molecules on the transformation of ACP to low crystalline apatite (Ap) was examined in Milli-Q® water, PBS, and α-MEM.

Abstract Soft and hard tissues possess distinct biological properties. Integrating the soft‐hard interface is difficult due to the inherent non‐osteogenesis of soft tissue, especially of anterior cruciate ligament and rotator cuff reconstruction. This property makes it difficult for tendons to be mineralized and integrated with bone in vivo. To overcome this challenge, a biomimetic mineralization strategy is employed to engineer mineralized tendons. The strategy involved infiltrating amorphous calcium phosphate precursors into collagen fibrils, resulting in hydroxyapatite deposition along the c‐axis. The mineralized tendon presented characteristics similar to bone tissue and induced osteogenic differentiation of mesenchymal stem cells. Additionally, the interface between the newly formed bone and tendon is serrated, suggesting a superb integration between the two tissues. This strategy allows for biomineralization of tendon collagen and replicating the hallmarks of the bone matrix and extracellular niche, including nanostructure and inherent osteoinductive properties, ultimately facilitating the integration of soft and hard tissues.

ABSTRACTBiogenic collagen membranes (BCM) have been widely used in guided bone regeneration (GBR) owing to their biodegradability during tissue integration. However, their relatively high degradation rate and lack of pro-osteogenic properties limit their clinical outcomes. It is of great importance to endow BCM with tailored degradation as well as pro-osteogenic properties. In this study, a fluoride-modified polymer-induced liquid precursor (PILP) based biomineralization strategy was used to convert the collagen membrane from an organic phase to an apatite-based inorganic phase, thus achieving enhanced anti-degradation performance as well as osteogenesis. As a result, three phases of collagen membranes were prepared. The original BCM in the organic phase induced the mildest inflammatory response and was mostly degraded after 4 weeks. The organic-inorganic mixture phase of the collagen membrane evoked a prominent inflammatory response owing to the fluoride-containing amorphous calcium phosphate (F-ACP) nanoparticles, resulting in active angiogenesis and fibrous encapsulation, whereas the inorganic phase induced a mild inflammatory response and degraded the least owing to the transition of F-ACP particles into calcium phosphate with high crystallinity. Effective control of ACP is key to building novel apatite-based barrier membranes. The current results may pave the way for the development of advanced apatite-based membranes with enhanced barrier performances.

Lithium is commonly prescribed as a mood stabilizer in a variety of mental health conditions, yet its molecular mode of action is incompletely understood. Many cellular events associated with lithium appear tied to mitochondrial function. Further, recent evidence suggests that lithium bioactivities are isotope specific. Here we focus on lithium effects related to mitochondrial calcium handling. Lithium protected against calcium-induced permeability transition and decreased the calcium capacity of liver mitochondria at a clinically relevant concentration. In contrast, brain mitochondrial calcium capacity was increased by lithium. Surprisingly, 7Li acted more potently than 6Li on calcium capacity, yet 6Li was more effective at delaying permeability transition. The size distribution of amorphous calcium phosphate colloids formed in vitro was differentially affected by lithium isotopes, providing a mechanistic basis for the observed isotope specific effects on mitochondrial calcium handling. This work highlights a need to better understand how mitochondrial calcium stores are structurally regulated and provides key considerations for future formulations of lithium-based therapeutics. [ABSTRACT FROM AUTHOR]

Amorphous calcium phosphate (ACP) which is a transient phase in the natural bio -mineralization process has recently gained the spotlight. This study aimed to assess the effect of the incorporation of nano -ACP (NACP) in a dental adhesive with/without surface treatment with silane coupling agent on bond strength. NACP was synthesized by the wet chemical precipitation technique. To characterize the structure of NACP, X-ray diffraction, scanning electron microscopy, and energy -dispersive X-ray spectroscopy were used. Forty molars were randomized into 4 groups of 10. The teeth were restored with composite resin and the bonding agent (one of the four groups). Adper Single Bond 2 was used as the control group. In the 4 wt% NACP group, NACP fillers were added to the bonding agent. In 0.4 wt% and 4 wt% SNACP groups, silanized NACP fillers were added to the bonding agent. Finally, the mode of failure of specimens was determined. Data were analyzed by one -way ANOVA and Tukey's post -hoc tests. P< 0.05 was considered statistically significant. The addition of 4 wt% non -silanized NACP decreased the bond strength compared with the control group (P< 0.05). The bond strength of the groups with silanized fillers was not significantly different from that of the control group. The addition of silanized NACP to dental adhesive had no significant adverse effect on bond strength, which is a promising finding to pave the way for the synthesis of bonding agents containing bioactive fillers. [ABSTRACT FROM AUTHOR]

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

Lithium is commonly prescribed as a mood stabilizer in a variety of mental health conditions, yet its molecular mode of action is incompletely understood. Many cellular events associated with lithium appear tied to mitochondrial function. Further, recent evidence suggests that lithium bioactivities are isotope specific. Here we focus on lithium effects related to mitochondrial calcium handling. Lithium protected against calcium-induced permeability transition and decreased the calcium capacity of liver mitochondria at a clinically relevant concentration. In contrast, brain mitochondrial calcium capacity was increased by lithium. Surprisingly, 7Li acted more potently than 6Li on calcium capacity, yet 6Li was more effective at delaying permeability transition. The size distribution of amorphous calcium phosphate colloids formed in vitro was differentially affected by lithium isotopes, providing a mechanistic basis for the observed isotope specific effects on mitochondrial calcium handling. This work highlights a need to better understand how mitochondrial calcium stores are structurally regulated and provides key considerations for future formulations of lithium-based therapeutics.

Biomaterials based on hydroxyapatite with controllable composition and properties are promising in the field of regenerative bone replacement. One approach to regulate the phase composition of the materials is the introduction of biopolymer-based additives into the synthesis process. The purpose of present study was to investigate the formation of hydroxyapatite-based hybrid materials in the presence of 6–24% platelet-poor plasma (PPP) additive, at a [Ca2+]/[PO43−] ratio of 1.67, pH 11, and varying maturing time from 4 to 9 days. The mineral component of the materials comprised 53% hydroxyapatite/47% amorphous calcium phosphate after 4 days of maturation and 100% hydroxyapatite after 9 days of maturation. Varying the PPP content between 6% and 24% brought about the formation of materials with rather defined contents of amorphous calcium phosphate and biopolymer component and the desired morphology, ranging from typical apatitic conglomerates to hybrid apatite-biopolymer fibers. The co-precipitated hybrid materials based on hydroxyapatite, amorphous calcium phosphate, and PPP additive exhibited increased solubility in SBF solution, which defines their applicability for repairing rhinoplastic defects. [ABSTRACT FROM AUTHOR]

The cytotoxicity of amorphous calcium phosphate (ACP) and chitosan lactate (ChOL) multifunctional and hybrid composite coatings on MRC-5 human lung fibroblast cell line was elucidated. ACP/TiO2 and ACP/TiO2 / /ChOL were deposited onto Ti by a novel in situ anodization/anaphoretic process at constant voltage. Cytotoxicity tests showed that there was no significant decrease in the survival of healthy MRC-5 cells exposed to composite samples without chitosan lactate, while there was an increase in the number of viable cells in the sample containing ChOL. These findings show that there was improved cell proliferation, differentiation and cell viability in the ChOL-containing sample, which makes ACP/TiO2 /ChOL coating a good candidate for applications in medicine and stomatology. [ABSTRACT FROM AUTHOR]

Biomimetic mineralized (Mg, Zn, Sr) carbonated amorphous calcium phosphate (cACP) containing biodegradable polycaprolactone (PCL) coating was prepared via spin coating technology. The main role of PCL was to provide a controlled release of cACP for a prolonged period of time and to act as a bioadhesive, providing better adherence than that of pure cACP powder. The cACP and the cACP-PCL composite layers were optimized as very thin, non-continuous films on the surface of a commercial titanium alloy, maintaining its surface roughness. The powder layer and the composite film were morphologically, chemically, and biologically tested. In vitro biocompatibility measurements were performed using MC3T3-E1 cells. The cell viability significantly increased when cACP coatings and cACP-PCL composite were applied to the pure Ti6Al4V substrate. The pure PCL coating and the titanium substrate indicated similar biocompatibility, however, adding cACP powders into the polymer solution resulted in increased cell viability. LDH and ALP measurements showed a large number of living cells on the surface of all samples. The cell morphology study by Calcein/DAPI staining as well as SEM measurements demonstrated a well-adhered and spread, confluent cell monolayer. The long-term release of bioactive ions in SBF solution indicated that the biodegradability of composite coating is slightly faster than the cACP powder layer. All in vitro measurements confirmed the suitability of the developed composite layer as a potential bone substitute and bioactive coating on middle- and long-term implants. [Display omitted] [ABSTRACT FROM AUTHOR]

A multitude of autogenous/allogeneic and semi-synthetic bone graft materials have been developed to reconstruct the defective bone tissue but with high bio-cost and potential environmental pollution. With high calcium content and several trace elements, chicken eggshells are no longer considered as wastes but attractive sources of high-value-added biomaterials. This study used chicken eggshells and synthetic hydroxyapatite (HAp) to synthesize amorphous calcium phosphate (ACP) bone graft materials, namely Control and Eggshell. The physiochemical characteristics, biosafety, and immunocompatibility of synthetic ACP particles were inspected. Their osteogenic activity was further investigated in a novel osteoblastic spheroids model. Eggshell ACP particles exhibited ideal cytocompatibility compared to the control ACP and were more resistant to re-crystallization. In osteoblastic spheroids, Eggshell ACP mediated typical osteogenic mRNA profiles of MC-3T3-E1 cells, accompanied by the increased formation of mineralized nodules and boosted synthesis of ECM proteins represented by OPN and collagen I. This study establishes a promising technique to synthesize stable, safe, and osteoinductive ACP graft particles from eggshell waste. Furthermore, the osteoblastic spheroids constructed in the present study provide a more practical model for biomaterial research, which reflect the three-dimensional interaction between host bone tissue and graft materials more realistically.

Featured Application: The article presents a novel fluoride particle technology for rapid remineralization, applicable for caries prevention and treatment of dentin hypersensitivity. This paper describes novel and innovative amorphous calcium magnesium fluoride phosphate (ACMFP) core-shell microparticles that may be applied in preventive dentistry for the prevention of caries and the treatment of dentin hypersensitivity. The particles can be synthesized with varied fluoride content, up to approximately 6 wt%, without any observable differences in morphology or crystallinity. Fluoride release from the particles is correlated to the fluoride content, and the particles are readily converted to fluoride-substituted hydroxyapatite or fluorapatite in a simulated saliva solution. The remineralization and dentin tubule occlusion potential of the particles was evaluated in vitro on acid-etched dentin specimens, and treatment with the ACMFP particles resulted in complete tubule occlusion and the formation of a dense mineralization layer. The acid resistance of the mineralization layer was improved compared to treatment with analogous particles without fluoride inclusion. A cross-sectional evaluation of dentin specimens after treatment revealed the formation of high aspect ratio fluorapatite crystals and poorly crystalline hydroxyapatite, respectively. The particles of the current study provide a single source vehicle of readily available calcium, phosphate, and fluoride ions for the potential remineralization of carious lesions as well as exposed dentin tubules for the reduction of hypersensitivity. [ABSTRACT FROM AUTHOR]

Amorphous calcium phosphate (ACP) is known as a precursor of hydroxyapatite (HAp) which is an inorganic main component of bone. The ACP gradually crystallizes to low crystalline apatite near human body temperature. If we introduce an active ingredient at the time of synthesis of ACP and we can introduce an ingredient effective for bone repair or an ingredient having functionality into the crystal structure of HAp, an active ingredientreleasing material responsive to bone metabolism would obtaine, and the protein might produce. Mn is an essential trace element in the living body and is present in the body as an active metal such as Mn-SOD (Mnsuperoxmutase) having an antioxidant activity and enhancing the activity of proteoglycan synthetase during bone formation. In this research, we try to introduce Mn into ACP, prepare cement using the obtained powder. In the synthetic powder, Mn was introduced at the same rate as the preparation. The obtained cement had crystallized and low-crytalline bone-like apatite composition. The porosity changed with the amount of Mn added. The cements exhibited protein adsorption properties regardress of the addition of Mn. It is expected that proteins involved in bone metabolism adsorb to the cement. [ABSTRACT FROM AUTHOR]

Calcium phosphates (CaPs) composites with silver nanoparticles (AgNPs) attract attention as a possible alternative to conventional approaches to combating orthopedic implant-associated infections. Although precipitation of calcium phosphates at room temperatures was pointed out as an advantageous method for the preparation of various CaP-based biomaterials, to the best of our knowledge, no such study exists for the preparation of CaPs/AgNP composites. Motivated by this lack of data in this study we investigated the influence of AgNPs stabilized with citrate (cit-AgNPs), poly(vinylpyrrolidone) (PVP-AgNPs), and sodium bis(2-ethylhexyl) sulfosuccinate (AOT-AgNPs) in the concentration range 5–25 mg dm−3 on the precipitation of CaPs. The first solid phase to precipitate in the investigated precipitation system was amorphous calcium phosphate (ACP). The effect of AgNPs on ACP stability was significant only in the presence of the highest concentration of AOT-AgNPs. However, in all precipitation systems containing AgNPs, the morphology of ACP was affected, as gel-like precipitates formed in addition to the typical chain-like aggregates of spherical particles. The exact effect depended on the type of AgNPs. After 60 min of reaction time, a mixture of calcium-deficient hydroxyapatite (CaDHA) and a smaller amount of octacalcium phosphate (OCP) formed. PXRD and EPR data point out that the amount of formed OCP decreases with increasing AgNPs concentration. The obtained results showed that AgNPs can modify the precipitation of CaPs and that CaPs properties can be fine-tuned by the choice of stabilizing agent. Furthermore, it was shown that precipitation can be used as a simple and fast method for CaP/AgNPs composites preparation which is of special interest for biomaterials preparation. [ABSTRACT FROM AUTHOR]

Monetite (MC) is a type of calcium phosphate cement (CPC). It has various morphologies, continuous degradation and absorption properties; however, its high porosity will affect its mechanical properties. There is minimal research on MC is immature. Amorphous calcium phosphate (ACP) is widely used and exhibits good biocompatibility; however, it is unstable. In this study, MC was combined with ACP at different weight ratios to form new types of bone cements. The mechanical properties, biocompatibility, and inductive ability for osteogenesis and osteoclasts of different MC/ACP composite bone cements were evaluated. The biocompatibility and effects on osteogenic and osteoclast differentiation of MC/ACP composite bone cements were investigated in vitro using mouse bone marrow mesenchymal stem cells (mBMMSCs) and mouse monocyte/macrophage cell line RAW 264.7. RAW 264.7 cells can differentiate into osteoclasts by osteoclast differentiation. The results indicated that the overall performance of the MC/ACP composite bone cement was better than that of the MC or ACP alone. Compared to the other groups, the biocompatibility of MC75 (75 wt% MC and 25 wt% ACP) was optimal; it was able to induce mBMMSCs osteogenesis to a greater extent. MC75 was the least favorable for the proliferation, migration, and differentiation of osteoclasts. The mechanical properties, setting time and injectability of MC75 meet clinical application requirements. This study demonstrated that MC75 is a promising bone cement for repairing bone defects. [ABSTRACT FROM AUTHOR]

A biodegradable amorphous carbonated calcium phosphate (caCP)-incorporated polycaprolactone (PCL) composite layer was successfully deposited by a spin coater. In this specific coating, the PCL acts as a bioadhesive, since it provides a better adherence of the coatings to the substrate compared to powder coatings. The caCP–PCL coatings were deposited and formed thin layers on the surface of a Si3N4–3 wt% MWCNT (multiwalled carbon nanotube) substrate, which is an emerging type of implant material in the biomedical field. The composite coatings were examined regarding their morphology, structure and biological performance. The biocompatibility of the samples was tested in vitro with MC3T3-E1 preosteoblast cells. Owing to the caCP–PCL thin layer, the cell viability values were considerably increased compared to the substrate material. The ALP and LDH tests showed numerous living cells on the investrigated coatings. The morphology of the MC3T3-E1 cells was examined by fluorescent staining (calcein and DAPI) and scanning electron microscopy, both of which revealed a well-spread, adhered and confluent monolayer of cells. All performed biocompatibility tests were positive and indicated the applicability of the deposited thin composite layers as possible candidates for orthopaedic implants for an extended period.

A large amount of research in orthopedic and maxillofacial domains is dedicated to the development of bioactive 3D scaffolds. This includes the search for highly resorbable compounds, capable of triggering cell activity and favoring bone regeneration. Considering the phosphocalcic nature of bone mineral, these aims can be achieved by the choice of amorphous calcium phosphates (ACPs). Because of their metastable property, these compounds are however to-date seldom used in bulk form. In this work, we used a non-conventional “cold sintering” approach based on ultrafast low-pressure RT compaction to successfully consolidate ACP pellets while preserving their amorphous nature (XRD). Complementary spectroscopic analyses (FTIR, Raman, solid-state NMR) and thermal analyses showed that the starting powder underwent slight physicochemical modifications, with a partial loss of water and local change in the HPO42- ion environment. The creation of an open porous structure, which is especially adapted for non-load bearing bone defects, was also observed. Moreover, the pellets obtained exhibited sufficient mechanical resistance allowing for manipulation, surgical placement and eventual cutting/reshaping in the operation room. Three-dimensional porous scaffolds of cold-sintered reactive ACP, fabricated through this low-energy, ultrafast consolidation process, show promise toward the development of highly bioactive and tailorable biomaterials for bone regeneration, also permitting combinations with various thermosensitive drugs.

Synthesis from mixed-anionic aqueous solutions is a novel approach to obtain active powders for bioceramics production in the CaO-SiO2-P2O5-Na2O system. In this work, powders were prepared using precipitation from aqueous solutions of the following precursors: Ca(NO3)2 and Na2HPO4 (CaP); Ca(NO3)2 and Na2SiO3 (CaSi); and Ca(NO3)2, Na2HPO4 and Na2SiO3 (CaPSi). Phase composition of the CaP powder included brushite CaHPO4‧2H2O and the CaSi powder included calcium silicate hydrate. Phase composition of the CaPSi powder consisted of the amorphous phase (presumably containing hydrated quasi-amorphous calcium phosphate and calcium silicate phase). All synthesized powders contained NaNO3 as a by-product. The total weight loss after heating up to 1000 °C for the CaP sample—28.3%, for the CaSi sample—38.8% and for the CaPSi sample was 29%. Phase composition of the ceramic samples after the heat treatment at 1000 °C based on the CaP powder contained β-NaCaPO4 and β-Ca2P2O7, the ceramic samples based on the CaSi powder contained α-CaSiO3 and Na2Ca2Si2O7, while the ceramics obtained from the CaPSi powder contained sodium rhenanite β-NaCaPO4, wollastonite α-CaSiO3 and Na3Ca6(PO4)5. The densest ceramic sample was obtained in CaO-SiO2-P2O5-Na2O system at 900 °C from the CaP powder (ρ = 2.53 g/cm3), while the other samples had densities of 0.93 g/cm3 (CaSi) and 1.22 (CaPSi) at the same temperature. The ceramics prepared in this system contain biocompatible and bioresorbable phases, and can be recommended for use in medicine for bone-defect treatment. [ABSTRACT FROM AUTHOR]

The aim of this study was to review the role of amorphous calcium phosphate (ACP) and ACPbased products in remineralization of enamel and dentin. An automated search was conducted for articles and data published on ACP-based remineralization systems. References of the selected articles were also searched manually for related articles. In the present study, the focus was placed on in-vitro studies on ACP-based remineralization systems published from 2011 to 2020. Out of the 600 articles, 11 articles were found to be suitable for our systematic review. These articles were analysed and together proved that ACP is a promising non - fluoride-based remineralizing agent, which furthermore can be combined with organic molecules, polymers, proteins, and ions for enhancing its stability and its remineralizing effect. ACP readily dissolves in saliva and acts as a reservoir of calcium and phosphate ions which are taken up by demineralized tissues; induce remineralization and balance the pH of the oral cavity. ACP is turning out to be more and more essential in dentistry. It remineralizes enamel and dentin better than crystalline calcium phosphates, and the new mineral deposit is similar in structure and composition to the dental tissues. It is considered that ACP will be put into use even more comprehensively soon due to the rapid growth of tissue engineering and applied material science. However, more long-term clinical studies are essential to compare the remineralization efficacy of ACP compared to other remineralizing systems. [ABSTRACT FROM AUTHOR]

Calcium phosphate (CaP) deposition during bone mineralization starts with the aggregation of Posner's clusters Ca 9 (PO 4) 6 into amorphous Ca-phosphate (ACP), which then transforms into crystalline CaP and finally maturates to hydroxyapatite (HA). Using dentin/enamel of human teeth as a model system, we show that the physiological inorganic polymer polyphosphate (polyP), a phosphate donor in mineralization, prevents the transition from amorphous to crystalline CaP at concentrations> 15 wt%. Stabilization of the amorphous phase of CaP by polyP is reversed by hydrolysis of the polymer by alkaline phosphatase (ALP), an enzyme that releases phosphate for mineralization. It is still present in calcified enamel and dentin, as shown here by immunostaining and enzyme activity measurements. The phase transfer into crystalline CaP can be prevented by the ALP inhibitor levamisole. Besides TEM and SEM, the modulating effects of polyP and ALP on the kinetics of the phase transition from amorphous to crystalline CaP are demonstrated and confirmed by XRD and FTIR analyses. Molecular modeling studies show that the polyP chains, due to their dimensions, are able to penetrate into the channels between the Posner molecules, preventing cluster association to ACP and impairing HA crystal formation. [Display omitted] • The physiological polyphosphate stabilizes the amorphous phase of tooth mineral. • This polymer prevents the transition of calcium phosphate into the crystalline phase. • The inhibition of phase transformation is abolished by alkaline phosphatase. • The polyphosphate hydrolyzing alkaline phosphatase is present in enamel and dentin. • Molecular modeling studies indicate an interference with Posner's cluster aggregation. [ABSTRACT FROM AUTHOR]