Acemannan coated, cobalt-doped biphasic calcium phosphate nanoparticles for immunomodulation regulated bone regeneration.

Biomaterials are used as scaffolds in bone regeneration to facilitate the restoration of bone tissues. The local immune microenvironment affects bone repair but the role of immune response in biomaterial-facilitated osteogenesis has been largely overlooked and it presents a major knowledge gap in the field. Nanomaterials that can modulate M1 to M2 macrophage polarization and, thus, promote bone repair are known. This study investigates a novel approach to accelerate bone healing by using acemannan coated, cobalt-doped biphasic calcium phosphate nanoparticles to promote osteogenesis and modulate macrophage polarization to provide a prohealing microenvironment for bone regeneration. Different concentrations of cobalt were doped in biphasic calcium phosphate nanoparticles, which were further coated with acemannan polymer and characterized. The nanoparticles showed >90% cell viability and enhanced cell proliferation along with osteogenic differentiation as demonstrated by the enhanced alkaline phosphatase activity and osteogenic calcium deposition. The morphology of MC3T3-E1 cells remained unchanged even after treatment with nanoparticles. Acemannan coated nanoparticles were also able to decrease the expression of M1 markers, iNOS, and CD68 and enhance the expression of M2 markers, CD206, CD163, and Arg-1 as indicated by RT-qPCR, flow cytometry, and ICC studies. The findings show that acemannan coated nanoparticles can create a supportive immune milieu by inducing and promoting the release of osteogenic markers, and by causing a reduction in inflammatory markers, thus helping in efficient bone regeneration. As per our knowledge, this is the first study showing the combined effect of acemannan and cobalt for bone regeneration using immunomodulation. The work presents a novel approach for enhancing osteogenesis and macrophage polarization, thus, offering a potent strategy for effective bone regeneration.

Implant stability and clinical outcome between implant placement using internal sinus floor elevation with alloplastic bone material grafting and without grafting: A 1-year randomized clinical trial.

OBJECTIVE: To compare implant stability and clinical outcome in implant placement between osteotome sinus floor elevation (OSFE) with biphasic calcium phosphate (BCP) which consisted of 30% of hydroxyapatite (HA) and 70% of beta-tricalcium phosphate (ß -TCP) grafting material and OSFE without using bone grafting material. The research questions is whether the BCP provides any benefit in OSFE or not. MATERIALS AND METHODS: Thirty patients (30 implants) with a single edentulous area of upper premolar or molar were randomly separated into OSFE with BCP (n = 15) and OSFE without grafting (n = 15). The patients were reevaluated 3, 6, 9, and 12 months after implant loading. The clinical assessments (implant stability quotient (ISQ), implant survival-failure rate, and surgical complication) were analyzed. Together with radiographic assessments in 2D (endo-sinus bone gain (ESBG), mean marginal bone change (MMBC)) and 3D (endo-sinus bone gain in CBCT (ESBG-CT)) were evaluated, with a mean follow-up time of at least 12 months of functional loading and prosthetic complication. RESULTS: 20 remaining implants (OSFE with BCP, n = 10; OSFE without grafting, n = 10) were analyzed. Mean ISQ was 79.18 ± 3.43 in 1-year follow-up (ISQ; OSFE with BCP = 78.72 ± 3.46, OSFE without grafting = 79.65 ± 3.52). ISQ in both groups increased steadily without significant differences in each follow-up. (p = 0.56). In radiographic evaluation, at 6-, 9-, and 12-month, OSFE without grafting group showed statistically significant lower MMBC (p < 0.05). The 1-year clinical results showed that 2 implants failed in OSFE with BCP, and 1 implant failed in OSFE without grafting. CONCLUSIONS: Graft material "BCP" (HA30:TCP70) coupled with OSFE presents no extraordinary benefit in implant stability, clinical and radiographic outcome in 1-year follow-up. CLINICAL RELEVANCE: Clinically, OSFE with grafting materials provides no additional benefit. CLINICAL TRIAL REGISTRATION NUMBER: TCTR20210517008 (date of registration: May 17, 2021).

Osteo-immunomodulatory effects of macrophage-derived extracellular vesicles treated with biphasic calcium phosphate ceramics on bone regeneration.

Literature on osteoimmunology has demonstrated that macrophages have a great influence on biomaterial-induced bone formation. However, there are almost no reports clarifying the osteo-immunomodulatory capacity of macrophage-derived extracellular vesicles (EVs). This study comprehensively investigated the effects of EVs derived from macrophages treated with biphasic calcium phosphate (BCP) ceramics (BEVs) on vital events associated with BCP-induced bone formation such as immune response, angiogenesis, and osteogenesis. It was found that compared with EVs derived from macrophages alone (control, CEVs), BEVs preferentially promoted macrophage polarization towards a wound-healing M2 phenotype, enhanced migration, angiogenic differentiation, and tube formation of human umbilical vein endothelial cells, and induced osteogenic differentiation of mesenchymal stem cells. Analysis of 15 differentially expressed microRNAs (DEMs) related to immune, angiogenesis, and osteogenesis suggested that BEVs exhibited good immunomodulatory, pro-angiogenic, and pro-osteogenic abilities, which might be attributed to their specific miRNA cargos. These findings not only deepen our understanding of biomaterial-mediated osteoinduction, but also suggest that EVs derived from biomaterial-treated macrophages hold great promise as therapeutic agents with desired immunomodulatory capacity for bone regeneration.

On the Ion Implantation Synthesis of Ag-Embedded Over Sr-Substituted Hydroxyapatite on a Nano-Topography Patterned Ti for Application in Acetabular Fracture Sites.

Introduction: There is an ongoing need for improved healing response and expedited osseointegration on the Ti implants in acetabular fracture sites. To achieve adequate bonding and mechanical stability between the implant surface and the acetabular fracture, a new coating technology must be developed to promote bone integration and prevent bacterial growth. Methods: A cylindrical Ti substrate mounted on a rotating specimen holder was used to implant Ca2+, P2+, and Sr2+ ions at energies of 100 KeV, 75 KeV and 180 KeV, respectively, using a low-energy accelerator to synthesize strontium-substituted hydroxyapatite at varying conditions. Ag2+ ions of energy 100 KeV were subsequently implanted on the as-formed surface at the near-surface region to provide anti-bacterial properties to the as-formed specimen. Results: The properties of the as-formed ion-implanted specimen were compared with the SrHA-Ag synthesized specimens by cathodic deposition and low-temperature high-speed collision technique. The adhesion strength of the ion-implanted specimen was 43 ± 2.3 MPa, which is well above the ASTM standard for Ca-P coating on Ti. Live/dead cell analysis showed higher osteoblast activity on the ion-implanted specimen than the other two. Ag in the SrHA implanted Ti by ion implantation process showed superior antibacterial activity. Discussion: In the ion implantation technique, nano-topography patterned surfaces are not concealed after implantation, and their efficacy in interacting with the osteoblasts is retained. Although all three studies examined the antibacterial effects of Ag2+ ions and the ability to promote bone tissue formation by MC3T3-E1 cells on SrHA-Ag/Ti surfaces, ion implantation techniques demonstrated superior ability. The synthesized specimen can be used as an effective implant in acetabular fracture sites based on their mechanical and biological properties.

Study of biphasic calcium phosphate (BCP) ceramics of tilapia fish bones by age.

Biphasic calcium phosphate (BCP), consisting of bioceramics such as HAp + ß-TCP and Ca10(PO4)6(OH)2 + Ca3(PO4)2, is a popular choice for optimizing performance due to its superior biological reabsorption and osseointegration. In this study, BCP was produced by calcining the bones of tilapia fish (Oreochromis niloticus) reared in net cages and slaughtered at an age ranging from 15 to 420 days. The bones were cleaned and dried, calcined at 900 °C for 8 h, and then subjected to high-energy grinding for 3 h to produce BCP powders. After the calcination process, the crystalline phase's hydroxyapatite (HAp) and/or beta-tricalcium phosphate (ß-TCP) were present in the composition of the bioceramic. The age-dependent variation in phase composition was confirmed by complementary vibrational spectroscopy techniques, revealing characteristic peaks and bands of the bioceramic. This variation was marked by an increase in HAp phase and a decrease in ß-TCP phase. Thermogravimetric Analysis (TGA) and Differential Thermal Analysis (DTA) from 25 to 1400 °C showed the characteristic mass losses of the material, with a greater loss observed for younger fish, indicating the complete removal of organic components at temperatures above 600 °C. Comparison of the results obtained by X-Ray Diffraction (XRD) and Rietveld refinement with Raman spectroscopy showed excellent agreement. These results showed that with temperature and environment control and adequate fish feeding, it is possible to achieve the desired amounts of each phase by choosing the ideal age of the fish. This bioceramic enables precise measurement of HAp and ß-TCP concentrations and Ca/P molar ratio, suitable for medical orthopedics and dentistry.

In vitro corrosion and cytocompatibility of Mg-Zn-Ca alloys coated with FHA.

In the field of orthopedics, it's crucial to effectively slow down the degradation rate of Mg alloys. This study aims to improve the degradation behavior of Mg-Zn-Ca alloys by electrodepositing fluorohydroxyapatite (FHA). We investigated the microstructure and bond strength of the deposition, as well as degradation and cellular reactions. After 15-30 days of degradation in Hanks solution, FHA deposited alloys showed enhanced stability and less pH change. The strong interfacial bond between FHA and the Mg-Zn-Ca substrate was verified through scratch tests (Critical loads: 10.73 ± 0.014 N in Mg-Zn-0.5Ca alloys). Cellular studies demonstrated that FHA-coated alloys exhibited good cytocompatibility and promoted the growth of MC3T3-E1 cells. Further tests showed FHA-coated alloys owed improved early bone mineralization and osteogenic properties, especially in Mg-Zn-0.5Ca. This research highlighted the potential of FHA-coated Mg-Zn-0.5Ca alloys in orthopedics applications.

Swept-source Raman spectroscopy of chemical and biological materials.

Significance: Raman spectroscopy has been used as a powerful tool for chemical analysis, enabling the noninvasive acquisition of molecular fingerprints from various samples. Raman spectroscopy has proven to be valuable in numerous fields, including pharmaceutical, materials science, and biomedicine. Active research and development efforts are currently underway to bring this analytical instrument into the field, enabling in situ Raman measurements for a wider range of applications. Dispersive Raman spectroscopy using a fixed, narrowband source is a common method for acquiring Raman spectra. However, dispersive Raman spectroscopy requires a bulky spectrometer, which limits its field applicability. Therefore, there has been a tremendous need to develop a portable and sensitive Raman system. Aim: We developed a compact swept-source Raman (SS-Raman) spectroscopy system and proposed a signal processing method to mitigate hardware limitations. We demonstrated the capabilities of the SS-Raman spectroscopy by acquiring Raman spectra from both chemical and biological samples. These spectra were then compared with Raman spectra obtained using a conventional dispersive Raman spectroscopy system. Approach: The SS-Raman spectroscopy system used a wavelength-swept source laser (822 to 842 nm), a bandpass filter with a bandwidth of 1.5 nm, and a low-noise silicon photoreceiver. Raman spectra were acquired from various chemical samples, including phenylalanine, hydroxyapatite, glucose, and acetaminophen. A comparative analysis with the conventional dispersive Raman spectroscopy was conducted by calculating the correlation coefficients between the spectra from the SS-Raman spectroscopy and those from the conventional system. Furthermore, Raman mapping was obtained from cross-sections of swine tissue, demonstrating the applicability of the SS-Raman spectroscopy in biological samples. Results: We developed a compact SS-Raman system and validated its performance by acquiring Raman spectra from both chemical and biological materials. Our straightforward signal processing method enhanced the quality of the Raman spectra without incurring high costs. Raman spectra in the range of 900 to 1200 cm-1 were observed for phenylalanine, hydroxyapatite, glucose, and acetaminophen. The results were validated with correlation coefficients of 0.88, 0.84, 0.87, and 0.73, respectively, compared with those obtained from dispersive Raman spectroscopy. Furthermore, we performed scans across the cross-section of swine tissue to generate a biological tissue mapping plot, providing information about the composition of swine tissue. Conclusions: We demonstrate the capabilities of the proposed compact SS-Raman spectroscopy system by obtaining Raman spectra of chemical and biological materials, utilizing straightforward signal processing. We anticipate that the SS-Raman spectroscopy will be utilized in various fields, including biomedical and chemical applications.

Hard tissue formation in pulpotomized primary teeth in dogs with nanomaterials MCM-48 and MCM-48/hydroxyapatite: an in vivo animal study.

BACKGROUND: This animal study sought to evaluate two novel nanomaterials for pulpotomy of primary teeth and assess the short-term pulpal response and hard tissue formation in dogs. The results were compared with mineral trioxide aggregate (MTA). METHODS: This in vivo animal study on dogs evaluated 48 primary premolar teeth of 4 mongrel female dogs the age of 6-8 weeks, randomly divided into four groups (n = 12). The teeth underwent complete pulpotomy under general anesthesia. The pulp tissue was capped with MCM-48, MCM-48/Hydroxyapatite (HA), MTA (positive control), and gutta-percha (negative control), and the teeth were restored with intermediate restorative material (IRM) paste and amalgam. After 4-6 weeks, the teeth were extracted and histologically analyzed to assess the pulpal response to the pulpotomy agent. RESULTS: The data were analyzed using the Kruskal‒Wallis, Fisher's exact, Spearman's, and Mann‒Whitney tests. The four groups were not significantly different regarding the severity of inflammation (P = 0.53), extent of inflammation (P = 0.72), necrosis (P = 0.361), severity of edema (P = 0.52), extent of edema (P = 0.06), or connective tissue formation (P = 0.064). A significant correlation was noted between the severity and extent of inflammation (r = 0.954, P < 0.001). The four groups were significantly different regarding the frequency of bone formation (P = 0.012), extent of connective tissue formation (P = 0.047), severity of congestion (P = 0.02), and extent of congestion (P = 0.01). No bone formation was noted in the gutta-percha group. The type of newly formed bone was not significantly different among the three experimental groups (P = 0.320). CONCLUSION: MCM-48 and MCM-48/HA are bioactive nanomaterials that may serve as alternatives for pulpotomy of primary teeth due to their ability to induce hard tissue formation. The MCM-48 and MCM-48/HA mesoporous silica nanomaterials have the potential to induce osteogenesis and tertiary (reparative) dentin formation.

Bone cement repair of malleus handle fractures: Intraoperative video and case report of two patients.

Isolated malleus fractures are a rare occurrence with few reported cases in the literature. Symptoms include sudden otalgia, hearing loss, tinnitus and aural fullness. Work-up and diagnosis are based on a combination of thorough anamnesis and careful otoscopic evaluation or high-resolution computer tomography. We present two cases of isolated malleus handle fractures who were diagnosed based on a combination of pneumatic otoscopy and tympanometry. Both fractures were surgically repaired using hydroxyapatite bone cement as showcased in the supplemental video material. Post-operative audiometry showed improvement in the pure-tone-average of both patients as well as normalisation of tympanometry. Isolated malleus fracture should be suspected in cases of sudden hearing loss and tinnitus following digital manipulation of the outer ear canal together with a conductive hearing loss with a mostly high-frequent air-bone-gap and hypercompliant tympanometry with hypermobility of the tympanic membrane on pneumatic insufflation. Surgical repair of the fracture using bone cement has good hearing outcomes and leads to improvement in auditory symptoms.

Strontium-Doped Hydroxyapatite Coating Improves Osteo/Angiogenesis for Ameliorative Graft-Bone Integration via the Macrophage-Derived Cytokines-Mediated Integrin Signal Pathway.

Polyethylene terephthalate (PET) artificial ligaments, renowned for their superior mechanical properties, have been extensively adopted in anterior cruciate ligament (ACL) reconstruction surgeries. However, the inherent bio-inertness of PET introduces formidable barriers to graft-bone integration, a critical aspect of rehabilitation. Previous interventions, ranging from surface roughening to chemical modifications, have aimed to address this challenge; however, consistently effective techniques for inducing graft-bone integration remain scarce. Our study employed advanced surface-coating methodologies to introduce strontium-doped hydroxyapatite (SrHA) onto PET ligaments. Detailed scanning electron microscopy (SEM) examinations revealed a uniform and integrative coating of SrHA on PET fibers. Furthermore, spectroscopic analysis confirmed the steady release of strontium ions from the coated surface under physiological conditions. In-depth cellular studies proved that extracellular strontium emanating from SrHA-coated PET (PET@SrHA) ligaments actively steers the M2 macrophage polarization. Additionally, macrophages (Mφs) manifested a heightened secretion of prohealing cytokines when exposed to PET@SrHA. Subsequent investigations showed that these cytokines acted as mediators, activating integrin signaling pathways among macrophages, vascular endothelial cells, and osteoblasts. As a direct consequence, an increased rate of angiogenesis and osteogenic differentiation was observed, vital for graft-bone integration following ACL reconstruction with PET@SrHA ligaments. From a biochemical standpoint, our results pinpoint strontium ions as influential immunomodulators, sculpting the graft-bone interface's immune environment. This insight presents the SrHA-coating technique as a viable therapeutic strategy, holding sound promise for improving angiogenesis and osseointegration outcomes during ACL reconstruction using PET-based grafts.

Examination of surface porosity of current pulp capping materials by micro-computed tomography (micro-CT) method.

When dental pulp is exposed, it must be covered with a biocompatible material to form reparative dentine. The material used, besides being biocompatible, should have an ideal surface structure for the attachment, proliferation and differentiation of dental pulp stem cells. This study aimed to evaluate the porosity of the microstructures of four pulp capping materials using micro-computed tomography (micro-CT). Biodentine, Bioaggregate, TheraCal and Dycal materials were prepared according to the manufacturer's instructions using 2 × 9 mm Teflon molds. A total of 60 samples, 15 in each group, were scanned using micro-CT. Open and closed pores and the total porosity of the microstructures of the materials were assessed. The findings obtained from the study were analyzed via the Kruskal-Wallis test followed by the Mann-Whitney U test. The porosity of Bioaggregate was significantly higher than that of Biodentine, Dycal and TheraCal in all porosity values. While Biodentine did not show a statistically significant difference in open and total porosity values from either TheraCal or Dycal, closed porosity values of Dycal were significantly higher than those of Biodentine and TheraCal. Because of the affinity of cells to porous surfaces, the pulp capping materials' microstructure may affect the pulp capping treatment's success. From this perspective, the use of Bioaggregate in direct pulp capping may increase the success of treatment.

Gene expression, micro-CT and histomorphometrical analysis of sinus floor augmentation with biphasic calcium phosphate and deproteinized bovine bone mineral: A randomized controlled clinical trial.

AIMS: The aim of this randomized controlled clinical trial was to compare the gene expression, micro-CT, histomorphometrical analysis between biphasic calcium phosphate (BCP) of 70/30 ratio and deproteinized bovine bone mineral (DBBM) in sinus augmentation. MATERIALS AND METHODS: Twenty-four patients in need for sinus floor augmentation through lateral approach were randomized into BCP 70/30 ratio or DBBM. After at least 6 months of healing, a total of 24 bone specimens were collected from the entire height of the augmented bone at the area of implant placement and underwent micro-CT, histomorphometric and gene expression analysis. The 12 bone specimens of BCP 70/30 ratio were equally allocated to micro-CT and histologic analysis (test group, n = 6) and gene expression analysis (test group, n = 6). Similarly, the 12 bone specimens of DBBM were also allocated to micro-CT and histologic analysis (control group, n = 6) and gene expression analysis (control group, n = 6). The newly formed bone, remaining graft materials and relative change in gene expression of four target genes were assessed. RESULTS: The micro-CT results showed no statistically significant difference in the ratio of bone volume to total volume (BV/TV ratio) for the two groups (BCP 41.51% vs. DBBM 40.97%) and the same was true for residual graft material to total volume (GV/TV ratio, BCP 9.97% vs. DBBM 14.41%). Similarly, no significant difference was shown in the histological analysis in terms of bone formation, (BCP 31.43% vs. DBBM was 30.09%) and residual graft area (DBBM 40.76% vs. BCP 45.06%). With regards to gene expression, the level of ALP was lower in both groups of bone grafted specimens compared with the native bone. On the contrary, the level of OSX, IL-1B and TRAP was higher in augmented bone of both groups compared with the native bone. However, the relative difference in all gene expressions between BCP and DBBM group was not significant. CONCLUSIONS: The BCP, HA/ß-TCP ratio of 70/30 presented similar histological and micro-CT outcomes in terms of new bone formation and residual graft particles with DBBM. The gene expression analysis revealed different gene expression patterns between augmented and native bone, but showed no significant difference between the two biomaterials.

Hydroxyapatite deposition disease, an overlooked differential diagnosis in the emergency department: a case series and review of literature.

Hydroxyapatite crystal deposition disease (HADD) poses diagnostic challenges in the emergency department (ED) as it may clinically present similarly to infection and other musculoskeletal conditions. Misdiagnosis often leads to unnecessary treatments and resource over-utilization. This review article provides an overview of HADD in seven patients who presented to the ED secondary to an acute presentation of this disease process. HADD is a prevalent pathology, which commonly involves the shoulder, followed by the hip, elbow, wrist, and knee. Predisposing risk factors, such as diabetes and certain genetic factors, have also been identified. Clinical history and imaging, particularly radiographs, play a vital role in diagnosing HADD, with characteristic calcification patterns observed in different stages of the disease. Conservative nonsurgical therapy is the mainstay of treatment, providing effective symptom relief in over 90% of cases. By recognizing HADD as a crucial differential diagnosis for patients with acute or chronic pain, healthcare resource utilization can be optimized, leading to improved patient care in the ED.

Preferentially Biodegradable Gypsum Fibers Endowing Invisible Microporous Structures and Enhancing Osteogenic Capability of Calcium Phosphate Cements.

It is known that hydroxyapatite-type calcium phosphate cement (CPC) shows appreciable self-curing properties, but the phase transformation products often lead to slow biodegradation and disappointing osteogenic responses. Herein, we developed an innovative strategy to endow invisible micropore networks, which could tune the microstructures and biodegradation of α-tricalcium phosphate (α-TCP)-based CPC by gypsum fibers, and the osteogenic capability of the composite cements could be enhanced in vivo. The gypsum fibers were prepared via extruding the gypsum powder/carboxylated chitosan (CC) slurry through a 22G nozzle (410 µm in diameter) and collecting with a calcium salt solution. Then, the CPCs were prepared by mixing the α-TCP powder with gypsum fibers (0-24 wt %) and an aqueous solution to form self-curing cements. The physicochemical characterizations showed that injectability was decreased with an increase in the fiber contents. The µCT reconstruction demonstrated that the gypsum fiber could be distributed in the CPC substrate and produce long-range micropore architectures. In particular, incorporation of gypsum fibers would tune the ion release, produce tunnel-like pore networks in vitro, and promote new bone tissue regeneration in rabbit femoral bone defects in vivo. Appropriate gypsum fibers (16 and 24 wt %) could enhance bone defect repair and cement biodegradation. These results demonstrate that the highly biodegradable cement fibers could mediate the microstructures of conventional CPC biomaterials, and such a bicomponent composite strategy may be beneficial for expanding clinical CPC-based applications.

Hydroxyapatite-Gold Modified Screen-Printed Carbon Electrode for Selective SARS-CoV-2 Antibody Immunosensor.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or coronavirus disease 2019 (COVID-19), is still spreading worldwide; therefore, the need for rapid and accurate detection methods remains relevant to maintain the spread of this infectious disease. Electrochemical immunosensors are an alternative method for the rapid detection of the SARS-CoV-2 virus. Herein, we report the development of a screen-printed carbon electrode immunosensor using a hydroxyapatite-gold nanocomposite (SPCE/HA-Au) directly spray-coated with the immobilization receptor binding domain (RBD) Spike to increase the conductivity and surface electrode area. The HA-Au composite synthesis was optimized using the Box-Behnken method, and the resulting composite was characterized by UV-vis spectrophotometry, TEM-EDX, and XRD analysis. The specific interaction of RBD Spike with immunoglobulin G (IgG) antibodies was evaluated by differential pulse voltammetry and electrochemical impedance spectroscopy methods in a [Fe(CN)6]4-/3- solution redox system. The IgG was detected with a detection limit of 0.0561 pg mL-1, and the immunosensor had selectivity and stability of 103-122% and was stable until week 7 with the influence of storage conditions. Also, the immunosensor was tested using real samples from human serum, where the results were confirmed using the chemiluminescent microparticle immunoassay (CMIA) method and showed satisfactory results. Therefore, the developed electrochemical immunosensor can rapidly and accurately detect SARS-CoV-2 antibodies.

The effect of the number of SO3- groups on the adsorption of anionic dyes by the synthesized hydroxyapatite/Mg-Al LDH nanocomposite.

In this study, a new nanocomposite of hydroxyapatite (HA)/Mg-Al layered double hydroxide (LDH) was successfully formed via a facile co-precipitation method and applied to adsorb three anionic dyes of alizarin red S (ARS), Congo red (CR), and reactive red 120 (RR120) differing in the number of SO3- groups from aqueous solution. Based on a combination of characterization analysis and adsorption experiments, HA/Mg-Al LDH nanocomposite showed better adsorption performance than HA and Mg-Al LDH. Using XRD and TEM analyses, the crystallinity and the presence of nanoparticles were confirmed. According to the SEM investigation, the Mg-Al LDH layers in the nanocomposite structure were delaminated, while HA nanorods were formed at the surface of Mg-Al LDH nanoparticles. The higher BET surface area of the novel HA/Mg-Al LDH nanocomposite compared to HA and Mg-Al LDH provided its superior adsorption performance. Considering an effective amount of adsorbent dosage, pH 5 was selected as the optimum pH for each of the three dye solutions. According to the results from the study of contact time and initial concentration, the pseudo-second-order kinetic (R2 = 0.9987, 0.9951, and 0.9922) and Langmuir isotherm (R2 = 0.9873, 0.9956, and 0.9727) best fitted the data for ARS, CR, and RR120, respectively. Anionic dyes with different numbers of SO3- groups demonstrated distinct adsorption mechanisms for HA and Mg-Al LDH nanoparticles, indicating that the adsorption capacity is influenced by the number of SO3- groups, with HA/Mg-Al LDH nanocomposite offering superior performance toward dyes with higher numbers of SO3- groups. Furthermore, ΔH° less than 40 kJ/mol, positive ΔS°, and negative ΔG° accompanied by the mechanism clarifying show physical spontaneous adsorption without an external source of energy and increase the randomness of the process during the adsorption, respectively. Finally, the regeneration study demonstrated that the nanocomposite could be utilized for multiple adsorption-desorption cycles, proposing the HA/Mg-Al LDH as an economically and environmentally friendly adsorbent in the adsorption of anionic dyes in water treatment processes.

Natural, biphasic calcium phosphate from fish bones for enamel remineralization and dentin tubules occlusion.

OBJECTIVES: A calcium phosphate extracted from fish bones (CaP-N) was evaluated for enamel remineralization and dentinal tubules occlusion. METHODS: CaP-N was characterized by assessing morphology by SEM, crystallinity by PXRD, and composition by ICP-OES. CaP-N morphology, crystallinity, ion release, and pH changes over time in neutral and acidic solutions were studied. CaP-N was then tested to assess remineralization and dentinal tubules occlusion on demineralized human enamel and dentin specimens (n = 6). Synthetic calcium phosphate in form of stoichiometric hydroxyapatite nanoparticles (CaP-S) and tap water were positive and negative controls, respectively. After treatment (brush every 12 h for 5d and storage in Dulbecco's modified PBS), specimens' morphology and surface composition were assessed (by SEM-EDS), while the viscoelastic behavior was evaluated with microindentation and DMA. RESULTS: CaP-N consisted of rounded microparticles (200 nm - 1 µm) composed of 33 wt% hydroxyapatite and 67 wt% ß-tricalcium phosphate. In acidic solution, CaP-N released calcium and phosphate ions thanks to the preferential ß-tricalcium phosphate phase dissolution. Enamel remineralization was induced by CaP-N comparably to CaP-S, while CaP-N exhibited a superior dentinal tubule occlusion than CaP-S, forming mineral plugs and depositing new nanoparticles onto demineralized collagen. This behavior was attributed to its bigger particle size and increased solubility. DMA depth profiling and SEM showed an excellent interaction between the newly formed mineralized structures and the pristine tissue, particularly at the exposed collagen fibrils. SIGNIFICANCE: CaP-N demonstrated very good remineralizing and occlusive activity in vitro, comparable to CaP-S, thus could be a promising circular economy alternative therapeutic agent for dentistry.

Azoximer bromide and hydroxyapatite: promising immune adjuvants in cancer.

Immune adjuvants are immune modulators that have been developed in the context of infectious vaccinations. There is currently a growing interest in immune adjuvants due to the development of immunotherapy against cancers. Immune adjuvant mechanisms of action are focused on the initiation and amplification of the inflammatory response leading to the innate immune response, followed by the adaptive immune response. The main activity lies in the support of antigen presentation and the maturation and functions of dendritic cells. Most immune adjuvants are associated with a vaccine or incorporated into the new generation of mRNA vaccines. Few immune adjuvants are used as drugs. Hydroxyapatite (HA) ceramics and azoximer bromide (AZB) are overlooked molecules that were used in early clinical trials, which demonstrated clinical efficacy and excellent tolerance profiles. HA combined in an autologous vaccine was previously developed in the veterinary field for use in canine spontaneous lymphomas. AZB, an original immune modulator derived from a class of heterochain aliphatic polyamines that is licensed in Russia, the Commonwealth of Independent States, and Slovakia for infectious and inflammatory diseases, is and now being developed for use in cancer with promising results. These two immune adjuvants can be combined in various immunotherapy strategies.

A novel fullerene composite material for directional oil control and antioxidant.

BACKGROUND: There are very few cosmetic ingredients that can target oil control and extend the wear time. Fullerenes have been reported to have excellent antioxidant capacity and a variety of biological activities, such as quenching free radicals, inhibiting lipid peroxidation, and promoting lipid flocculation. OBJECTIVE: The purpose of applying foundation makeup on the face is to make the skin color even, but the secretion and oxidation of skin oil will make the makeup mottled and dull. In order to solve this problem, a fullerene composite material that can directionally absorb oil and resist oil oxidation has been developed. METHODS: Fullerenes and hydroxyapatite composite was prepared by high pressure homogenization under alkaline condition. The indicated morphology and structure were characterized by SEM, UV-Vis, Raman, and XRD. The oil absorption capacity was determined by adding the C60-hydroxyapatite composite to a mixed solution of hexane and oil, shaking for 1 h, filtering, analyzed by GC-MS, and calculating the oil absorption by external standard method. Artificial sebum was prepared by adding different mass of water and oleic acid to screen the optimum ratio. C60-hydroxyapatite mixture and C60-hydroxyapatite composite were added to the artificial sebum to test the oil-absorbing capacity of the materials. The hydroxyl radical scavenging ability of C60-hydroxyapatite composite containing different fullerene contents was measured by X-band ESR spectroscopy, and the long-term radical scavenging ability of the composites was tested in comparison with VC. Antioxidant experiment is adding C60-hydroxyapatite composite material, and hydroxyapatite to oleic acid, then the UV light irradiation is aimed to accelerate the oxidation of oleic acid. Oleic acid act as a control group, and make the detection of oleic acid peroxide value after 7 days. The safety of the materials was tested by using culture media to soak the C60-hydroxyapatite composite for 24 h and then used to culture cells. RESULTS: The characterization of SEM, UV-Vis, Raman, and XRD showed that fullerene clusters were dispersed on the surface of hydroxyapatite stably, and they formed a stable composite. The adsorption rates of C60-hydroxyapatite composites for oleic acid, phenyl trimethicone, caprylic capric glyceride, isooctyl palmitate, mineral oil, olive oil, and dimethicone were 60.5%, 9.3%, 9.15%, 5.24%, 2.94%, 1.01%, and 0%, respectively. The flocculation amount of artificial sebum was 5.9 g per gram of C60-hydroxyapatite mixture and 24.2 g per gram of C60-hydroxyapatite composite. C60-hydroxyapatite composites have excellent quenching ability for hydroxyl radicals. When the fullerene content is 1, 2, 3, and 4 mg/kg, the quenching rates are 25.02%, 39.57%, 49.75%, and 62.24%, respectively. The quenching effect was enhanced with the increase of fullerene content, and it had strong long-term antioxidant properties. It can also be proved that C60-hydroxyapatite composites have strong antioxidant capacity through antioxidant experiments. The peroxide value of oleic acid on Day 0 was 2.8, and after 7 days of UV irradiation, the peroxide values of blank control, hydroxyapatite group, C60-hydroxyapatite composite containing 0.5% and 1% fullerenes four groups of materials were 8.02 meq O2/kg, 7.98 meq O2/kg, 7.11 meq O2/kg, and 6.87 meq O2/kg, respectively. The cell activity was 20.94% and 99.2% after the cells were cultured for 24 h using C60-hydroxyapatite composite and hydroxyapatite extracts, respectively, and the addition of fullerene was able to significantly increase the cell activity. CONCLUSION: Fullerene hydroxyapatite complex has excellent directional oil absorption characteristics, which can effectively remove free radicals and reduce skin oil oxidation.

Are hydroxyapatite-based biomaterials free of genotoxicity? A systematic review.

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.