Bicalcium Phosphate Research Articles

Bicalcium Phosphate as an Asset in Regenerative Therapy.

After a loss of a tooth, alveolarbone resorption is immutable, leaving the area devoid of sufficient bone quality and mass for a successful and satisfactory implant or any other dental treatment. To treat this problem of irreversible bone loss, bone grafting is the primary solution and a well-accepted technique. The use of bone grafting procedures has increased in recent years. This review is about the various bone grafting techniques and best-situated material available currently along with their trump cards and limitations. In the thorough discussion regarding bone grafting materials and their substitutes, one alloplastic material has shown unbeaten and the most satisfactory properties than any other material, "bicalcium phosphate" (BCP). BCP is a mixture of hydroxyapatite (HA) and beta-tricalcium phosphate (B-TCP) usually obtained through sintering calcium-deficient apatite (CDA) at or above 700°C or by other methods such as hydrolysis or precipitation. The review also shows comparative studies done to understand the effect, most adequate balance, and impact of ratios of HA/B-TCP on the properties, structure, and success rate of this material. The objective of the review is to enlighten the principal characteristic of the most likely used bone graft material presently, i.e., BCP. The most impeccable characteristic of BCP is its capability to osteointegrate, which results in a superior interface. This interface depicts a dynamic process that includes physicochemical reactions, crystal-protein interactions, cell and tissue colonization, and bone remodeling. BCP has certain essential properties that could be put forth as its advantage over any other substitute. These properties include bioactivity, osteointegration, osteoinduction, osteogenesis, and biodegradation, which are mostly governed by modifying the HA/B-TCP ratio. Other applications of BCP are feasible, such as in drug administration and scaffolds for tissue engineering.

Usability Of Three-dimensional Printing in Maxillofacial Surgery: A Narrative Review

Purpose: The three-dimensional (3D) printing method is a modern approach in which different custom designs are fabricated with high complexity according to the patient’s need. This narrative review aimed to highlight the materials used in 3D printers for medical use, especially in the field of oral and maxillofacial surgery. Methods: PubMed, Web of Sciences, and Google Scholar were searched for the relevant studies, and after meeting the inclusion criteria, articles were studied, and focused points were highlighted. Results: s: Synthetic and natural materials used in 3D printing include hydroxyapatite, tricalcium phosphate, bicalcium phosphate, apatite–wollastonite glass ceramics, stem cells, and collagen. The most frequent clinical applications include dental implants, maxillofacial trauma, facial cosmetics, orthognathic surgery, maxillofacial oncology, and maxillofacial reconstruction. Anatomical models and surgical instructions were the most often printed objects. The key benefits were increased surgical precision and a shorter operating time. The cost of the items, the length of the manufacturing process when printed by the industry, and legal concerns were the main drawbacks. Conclusion: The 3D models are beneficial for surgeons as they can save time and even human life. In the future, additional research should be done on the modeling, efficacy, and safety of natural materials, and systematic reviews and meta-analyses should be conducted for a better understanding.

Coupling BCP Ceramics with Micro‐Vibration Stimulation Field for Cascade Amplification from Immune Activation to Bone Regeneration

AbstractThe osteoimmunology has revealed that immune system plays an important role in maintaining bone metabolism and remodeling. As long‐term physiological factor in bone, mechanical stimulation such as micro‐vibration stimulation (MVS) exerts effects on regulating osteogenesis and immune response. In this study, the osteo‐immunodulatory effects of bicalcium phosphate (BCP) ceramics coupled with MVS are investigated. This results find that the combination of BCP ceramics and MVS may exert synergistic effects on the polarization and functional status of macrophages through activating plasma membrance Ca2+ ATPase (PMCA) channel, reducing the intracellular calcium ion concentration, and inhibiting downstream extracellular signal‐regulated kinase (ERK)1/2 signaling pathway. BCP ceramics coupled MVS could drive the macrophage polarization to wound‐healing M2 phenotype to decrease the production of pro‐inflammatory factors, enhance the secretion of anti‐inflammatory cytokines and growth factors such as transforming growth factor (TGF)‐β1 and bone morphogenetic protein (BMP)‐2. Moreover, BCP and MVS‐modulated macrophage secretion pattern can trigger the BMP/TGF‐Smad signaling pathways to induce osteoblastic differentiation of bone marrow mesenchymal stromal cells (BM‐MSCs) in vitro, and maintain cellular viability and promote the formation of collagen‐rich osteoid like tissues and mature blood vessels in vivo. This study demonstrates that the introduction of mechanical stimuli like non‐invasive MVS is an effective strategy to improve bone repair effects of biomaterials through endowing them with superior osteo‐immunodulatory capacity.

Dielectric and transport properties of copper-substituted bi-calcium phosphate nanocomposites: Its structural and microstructural evaluation

A detailed investigation of dielectric and electrical transport behavior of the compressed polycrystalline copper substituted biphasic calcium phosphate (Cu-BCP) [hydroxyapatite (HAp) + beta-tricalcium phosphate (β-TCP)] was carried out. Their structural, microstructural, and chemical characterizations confirmed the phase purity, constituent phase percentages, and bulk porosity of the prepared nanocomposite due to Cu substitution. Due to increased Cu doping, the structural modifications helped to enhance dielectric permittivity with low dielectric loss. The impurity ion-induced defect states, secondary phase percentage, bulk porosity, and crystallinity have influenced the space charge polarization process within the grain-grain boundary-electrode interior. Porosity and phase regulated dielectric properties, unique impedance behavior, and rapidly increasing nonlinear leakage current suggest the suitability of the Cu-BCP nanocomposite in future device-based electroceramic applications.

Functional Genomic and Immune Response Characterization of PTEN Loss: Therapeutic Implications for Myeloma

PTEN (phosphatase and tensin homolog) is a known tumor suppressor gene (TSG) in solid tumors and hematologic malignancies, including multiple myeloma (MM), yet several aspects of its biology and clinical implications remain incompletely understood in MM. For instance, PTEN mutations/deletions are infrequent in newly diagnosed MM in the CoMMpass study (6 and 9 cases with heterozygous mutations or loss of one PTEN gene copy, respectively in 957 patients, IA16; no evidence of bi-allelic loss), and there is no enrichment for PTEN transcript suppression or biallelic PTEN loss at relapse. Moreover, while MM cell lines are considered to reflect advanced relapsed/refractory MM, nearly all are PTEN-proficient (with notable exceptions e.g. biallelic loss in OPM2). These considerations raise a question whether PTEN loss is indeed functionally associated with a competitive advantage for MM cells compared to their PTEN-proficient counterparts. In genome-scale CRISPR-Cas9 gene editing (knockout, KO) screens we observed that 16/19 MM cell lines exhibited CERES or CHRONOS scores >0.4, consistent with the proposed role of PTEN as a negative regulator of survival and proliferation: the 3 outlier cell lines included OPM2 (biallelic PTEN deletion) and 2 other lines (SKMM2 and AMO1) with no obvious genetic events suppressing PTEN function or causing constitutive activation of PI3K/Akt/mTOR signaling. We performed subgenome-scale CRISPR KO screens with focused libraries of single guide RNAs (sgRNAs) for several known (including PTEN) or candidate TSGs and control sgRNAs from MM and other tumors in vitro and confirmed that in vitro enrichment of PTEN KO in several PTEN-proficient (but not -deficient lines), consistent with the genome-scale CRISPR study results. These observations were further confirmed with in vitro competition assays where isogenic Cas9+ cells transduced with sgRNAs against PTEN or olfactory receptor (OR) genes (as DNA-cutting negative controls) were mixed, cultured for 4-12 weeks and DNA sequenced for the distribution of their sgRNAs, and determined a significant relative enrichment of PTEN KOs compared to their OR KO counterparts. Importantly, when cells harboring focused sub-genome scale sgRNA library were implanted in vivo in a bicalcium phosphate scaffold-based bone marrow (BM)-like model with a “humanized” mesenchymal bone stromal cell compartment, we observed that CRISPR KO of PTEN represented the top enriched gene perturbation in the PTEN-proficient MM cell lines MM.1S and KMS11 (not the AMO1 line) in vivo, consistent with the in vitro results. Collectively, these observations indicate that while PTEN deficiency is infrequent in newly diagnosed MM patient samples and in preclinical cell line models that reflect advanced disease, PTEN KO is associated with major “fitness” advantage for MM cells in preclinical in vitro and in vivo xenograft models, i.e. systems in which tumor cell “fitness” does not account for potential immunogenicity of human tumor cells. We hypothesized that PTEN KO remain highly immunogenic which curtails their “fitness” advantage: indeed, we observed in a series of CRISPR KO screens in PTEN-proficient cell lines from MM, other hematologic malignancies or solid tumors, PTEN loss was not associated with increased resistance to allogeneic donor-derived NK cells (in-house studies) or T-cell treatment (e.g. 41T, RENCA cells; GSE149933). In fact, for some MM cell lines (e.g. MM1S, KMS11), PTEN KO led to more pronounced sensitivity to NK cells (compared to control OR KOs) in genome-scale or focused CRISPR screens, and in validation experiments with individual sgRNAs for PTEN (vs. OR gene sgRNAs). While our functional genomic studies document that PTEN loss confers a generalizable “fitness advantage” for MM lines in vitro and in immunocompromised in vivo models, the limited, if any, association of advanced MM with PTEN loss raises intriguing questions about the potentially complex role of PTEN as a TSG. While alternative hypotheses are plausible, our results point to the immune responses of PTEN-deficient tumor cells as an additional factor that can reconcile our integrated observations in molecular annotated clinical samples and preclinical functional genomic studies. DisclosuresTsherniak: Cedilla Therapeutics: Consultancy; Foghorn Therapeutics: Consultancy; The Center for Protein Degradation: Consultancy; SAB: Membership on an entity's Board of Directors or advisory committees. Licht: Epizyme: Research Funding. Boise: Abbvie: Consultancy; AstraZeneca: Consultancy, Research Funding. Mitsiades: Arch Oncology: Research Funding; Karyopharm: Research Funding; Sanofi: Research Funding; FIMECS: Consultancy, Honoraria; EMD Serono: Research Funding; Abbvie: Research Funding; Nurix: Research Funding; Janssen/Johnson & Johnson: Research Funding; BMS: Research Funding; Ionis Pharmaceuticals: Consultancy, Honoraria; Fate Therapeutics: Consultancy, Honoraria; Adicet Bio: Membership on an entity's Board of Directors or advisory committees; TEVA: Research Funding; Novartis: Research Funding; H3 Biomedicine: Research Funding.

Digestibilidade de fontes proteicas e disponibilidade de fosfatos inorgí­¢nicos em três fases de desenvolvimento da tilápia-do-nilo

A digestibilidade aparente dos nutrientes de ingredientes proteicos e fosfatos inorgí­¢nicos foi comparada em três diferentes fases de desenvolvimento da tilápia-do-nilo. Os ingredientes testados foram farinha de peixe, farinha de ví­­sceras de aves, farinha de carne e ossos, glúten de milho, farelo de soja, farelo de algodão, fosfato monobicálcico, fosfato bicálcico, fosfato monopotássico e ácido fosfórico. Os coeficientes de digestibilidade aparente (CDAs) de matéria seca, proteí­­na, energia, P, Ca e Mg foram determinados com peixes de 25 g, 250 g e 500 g. Concluiu-se que a capacidade da tilápia-do-nilo de digerir os alimentos e absorver os nutrientes é dependente do peso corporal e das caracterí­­sticas do alimento avaliado. Houve tendência de melhor aproveitamento de nutrientes dos alimentos de origem animal e das fontes inorgí­¢nicas pelos peixes de 25 g. Os peixes de 250 g e 500 g mostraram melhor aproveitamento dos nutrientes das fontes proteicas de origem vegetal quando comparados aos peixes de 25 g.

English

Phosphorus solubilizers naturally acidify rhizospheric soil and increase phosphorus availability; therefore, their evaluation may help to reduce phosphorus fertilizer use. This work aimed to evaluate the different selection methods and select inorganic phosphorus-solubilizing bacteria as potential plant-growth promoters. Bacterial isolates obtained from sugarcane roots and soil were tested using solid growth media containing bicalcium phosphate and Irecê Apatite ground rock phosphate as phosphorus sources. Seven isolates with high (3), moderate (3) and low solubilization indices (1) and the Pseudomonas fluorescens R-243 strain were tested in two liquid growth media, followed by the pH and soluble P in the solution. The same isolates, in the absence of inoculation, were tested in Leonard jars with two high- and low-solubility sources using cowpea as a test species. Forty-four days after planting aboveground dry mass, the phosphorus content and total aboveground phosphorus and substratum phosphorus contents were evaluated. The growth media affected phosphorus solubilization by the bacteria. Evaluation of liquid media was the most reliable method for analyzing bicalcic phosphorus solubilization by the bacteria not linked to pH reduction. Isolates UAGC 17, 19 and 65 should be better studied because they were the best solubilizers in culture media; however, they did not demonstrate the same efficiency when inoculated on cowpea. Key words: Solubilization, phosphate, P-solubilizing-microorganisms.

Comparative In Vitro Osteoinductivity Study of HA and α‐TCP/HA Bicalcium Phosphate

A bicalcium phosphate (BCP) bioceramic comprising α‐tricalcium phosphate (α‐TCP) and hydroxyapatite (HA) was prepared by a two‐step sintering. The microstructure of the BCP bioceramic was investigated using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X‐ray diffraction. The in vitro osteoinductivity was evaluated by culturing MG63 osteoblast‐like cells on the BCP bioceramic. Results showed that the BCP bioceramic comprising α‐TCP and HA in a moderate ratio possessed a hardness of 93.7 Hv. The cells spread faster on the BCP bioceramic than those on the commercial HA. It suggested that the BCP bioceramic can enhance osteoinductivity in vivo.

Bicalcium Phosphate Filling-Up After Calvarial Unicortical Harvesting in Maxillofacial Surgery

The calvarium is one of the most common donor sites for bone grafting in maxillofacial and craniofacial surgery. The quality of the bone and the few after-effects that arise in calvarium make it a very good choice for reconstruction, especially in preprosthetic surgery. Nevertheless, calvaria harvesting of the outer table can leave a depression on the scalp, which can be perceptible and palpable. This point is always difficult to assume for patients. This absence of outer-layer reconstruction of the skull could also lead to a modification of biomechanical characteristics and fragility of the skull. This is the reason why we decided to fill up the donor site with an osseoconductive biomaterial: bicalcium phosphate. To evaluate this reconstruction, we reviewed 20 patients who have undergone this procedure. All patients have been seen 6 months after surgery, 11 of them with computed tomographic scans of the donor site. An aesthetic evaluation of the result was made by the patient through a questionnaire. With computed tomographic scans, we made qualitative and quantitative evaluations of the donor site. For 2 patients of them, histologic examination was performed to evaluate newly formed bone. The results of this study suggest that filling in the donor site with bicalcium phosphate improves the tolerance of calvaria harvesting. Bone colonization of the osseoconductive biomaterials leads to the formation of a new outer table of the skull. Taking into account the quality of the calvarial bone and the restoration of the donor site, calvaria harvesting is, in our hands, one of the best choices in craniofacial and maxillofacial reconstruction.

<i>In Vitro</i> and <i>In Vivo</i> Evaluation Of Calcium Phosphate Bone Graft Substitutes

Calcium phosphate ceramics such as hydroxy apatite (HA), β-tricalcium phosphate (β-TCP) and bicalcium phosphate (BCP) have been used as a bone graft biomaterial because of their good biocompatibility and similarity of chemical composition to natural bones. To increase the mechanical and osteoconductive properties, the granules and spongy type porous bone graft substitutes were prepared by fibrous monolithic process and polyurethane foam replica methods, respectively. The pore sizes obtained using these approaches ranged between 100-600 µm. The cytotoxicity, cellular proliferation, differentiation and ECM deposition on the bone graft substitutes were observed by SEM and confocal microscopy. Moreover, the scaffolds were implanted in the rabbit femur. New bone formation and biodegradation of bone graft were observed through follow-up X-ray, micro-CT analysis and histological findings. After several months (2, 3, 6, 12 and 24 months) of implantation, new bone formation and ingrowths were observed in defect sites of the animal by CaP ceramics and 2 to 3 times higher bone ingrowths were confirmed than that of the normal trabecular bones in terms of total bone volume (BV).

Dose assessment at a phosphate industry landfill using solid state detectors

The industrial landfill “Racó de la Pubilla” is located at Flix (Tarragona, Spain) and contains residues from a factory that produces bicalcium phosphate using phosphorite. The main aim of the study was the determination of the environmental radiological conditions in the landfill in order to estimate the effective dose received by workers and the potential impact on the surrounding area. With these objectives in mind, a system based on LiF:Mg,Cu,P thermoluminescent detectors (TLD) and electrets was used. The main dosimetric characteristics of the TLD system are presented (LID, energy response, isotropy, etc.), as well as the results of the influence of environmental conditions on the electrets. The evaluation of the gamma ambient dose equivalent measured at the landfill by the TLD technique gives a maximum value of approximately 200 nSv/h, but most of the measurement points were close to the unaltered site (80 nSv/h). In addition, average radon concentrations of 30 Bq / m 3 were measured, slightly higher than the reference value. The effective dose due to the natural radioactive components of the waste is lower than 1 mSv/year. The use of LiF:Mg,Cu,P, with a sensitivity 30–40 times higher than LiF:Mg,Ti, and electrets for radon measurements allow short measurement periods, thus providing an easy assessment of the radiological risk of the studied facility.

Pseudomonas rhizosphaerae sp. nov., a novel species that actively solubilizes phosphate in vitro

A bacterial strain (designated IH5(T)), isolated from rhizospheric soil of grasses growing spontaneously in Spanish soil, actively solubilized phosphates in vitro when bicalcium phosphate was used as a phosphorus source. This strain was Gram-negative, strictly aerobic, rod-shaped and motile. The strain produced catalase, but not oxidase. Cellulose, casein, starch, gelatin, aesculin and urea were not hydrolysed. Growth was observed with many carbohydrates as the carbon source. The main non-polar fatty acids detected were hexadecenoic acid (C(16 : 1)), hexadecanoic acid (C(16 : 0)) and octadecenoic acid (C(18 : 1)). The hydroxy fatty acids detected were 3-hydroxydecanoic acid (C(10 : 0) 3-OH), 3-hydroxydodecanoic acid (C(12 : 0) 3-OH) and 2-hydroxydodecanoic acid (C(12 : 0) 2-OH). Phylogenetic analysis of 16S rRNA indicated that this bacterium belongs to the genus Pseudomonas in the gamma-subclass of the Proteobacteria and that the closest related species is Pseudomonas graminis. The DNA G+C content was 61 mol%. DNA-DNA hybridization showed 23 % relatedness between strain IH5(T) and P. graminis DSM 11363(T). Therefore, strain IH5(T) belongs to a novel species from the genus Pseudomonas, for which the name Pseudomonas rhizosphaerae sp. nov. is proposed (type strain, IH5(T)=LMG 21640(T)=CECT 5726(T)).

Nutritional and microbiological evaluation of meat and bone meal produced in the state of Minas Gerais

The present study investigated the chemical composition and metabolizable energy levels of ten meat and bone meals (MBM) produced in Minas Gerais state (Experiment I) and evaluated the growth performance of broilers fed with diets containing those MBM (Experiment II). In the first experiment, energy values (apparent metabolizable energy [AME] and corrected apparent metabolizable energy [AMEn]) of ten different MBM were determined using the traditional method with total collection of excreta. Four hundred forty 21 day-old Hubbard broilers were used. A reference corn and soybean meal-based diet was replaced in 20% by the feed containing MBM to be tested. A completely randomized experimental design was used with eleven treatments (one reference diet and ten MBM), four repetitions per treatment and 10 birds per repetition (5 males and 5 females). In the second experiment, five MBMs from the ten analyzed in Experiment 1 were used as phosphorus source and compared to a diet containing bicalcium phosphate. The growth performance of the broilers fed with these diets was analyzed, considering two ages of the onset of MBM inclusion in the diet (1 or 7 days of age). One-day-old Hubbard broilers (1,320 birds) were housed in 44 plots with 30 birds per experimental unit. The experiment consisted of 11 treatments in a 5x2 factorial arrangement, with five sources of MBM, two ages for the onset of inclusion, and a reference treatment without addition of MBM. The results obtained showed a great variation in the chemical composition and apparent metabolizable energy of the evaluated meals. No significant differences were found on the performance of broilers fed diets with different MBM or the diet with bicalcium phosphate as phosphorus source. The performance of broilers was not significantly influenced by the onset of MBM inclusion in the diets.

Effect of dietary fluorine from Araxá rock phosphate on the hepatic production of cyclic-adenosine monophosphate in broilers

The cyclic adenosine 3’, 5’-monophosphate (cAMP) production was evaluated in liver thin sections of broiler chicks fed on a experimental diet containing bicalcium phosphate or Araxá rock phosphate (ARP) as source of P, with a high content of fluorine, at different ages: from the first to the 42nd and from the 21st to the 42nd day of age. The intake of the ARP formulated diet starting from birth elicited an increase of cAMP production in broiler liver. However, when this diet was offered after the 21st day of age, the hepatic cAMP production in broilers was not significantly (P>0.05) affected, suggesting that the effect of high fluorine present in Araxá rock phosphate, on hepatic cAMP of broiler chicks depends on the age in which the experimental diet is started.

Avaliação nutricional do fósforo disponível de quatro fontes de fósforo para suínos em fase de terminação

O experimento teve como objetivo avaliar a inclusão de fontes de fósforo (P), considerando-se seu fósforo disponível, sobre o desempenho de suínos em fase de terminação (60 a 100kg). As fontes avaliadas foram: fosfato bicálcico padrão (FBP), fosfato supertriplo (FST), fosfato monoamônio (FMA) e a consorciação de fosfato bicálcico padrão (80%) com o fosfato de Patos de Minas (FPM - 20%). Foram utilizados 32 leitões, machos, castrados, mestiços de raça tipo carne, com peso médio de 60kg. O delineamento experimental utilizado foi o inteiramente ao acaso, com 4 tratamentos, com 4 repetições de 2 animais cada. As dietas foram isoprotéicas e isoenergéticas adequadas para a fase de terminação. Avaliaram-se o ganho de peso, o consumo de ração, a conversão alimentar e o consumo de flúor. Foram observadas diferenças significativas (P<0,05) entre tratamentos somente para ganho de peso e consumo de ração. O fosfato supertriplo foi significativamente inferior aos demais fosfatos, apresentando o menor ganho de peso (37,4kg). Porém, não houve diferença no ganho de peso entre os animais alimentados com os fosfatos FBP (40,45kg), FMA (40,45kg) e a mistura de 20% de FPM e 80% de FBP (45,10kg). Também não houve diferença no consumo de ração em função dos fosfatos FBP (133,91kg), FMA (144,70kg) e da mistura de 20% FPM e 80% de FBP (146,71kg). A conversão alimentar não foi afetada pelos fosfatos, variando entre 3,24 e 3,54. O consumo de flúor, diferiu estatisticamente nos quatro tratamentos, sendo maior nos animais alimentados com 20% de FPM (30,80g), seguido do FST (9,24g), FBP (3,65g) e FMA (2,16g). Os níveis de fósforo disponível das fontes avaliadas revelaram-se adequados para suínos em fase de terminação, portanto a adoção dos valores de biodisponibilidade do fósforo dos suplementos deve ser um critério recomendado nas formulações e rações. As fontes de fósforo testadas podem ser recomendadas para utilização em rações de suínos em fase de terminação, ressaltando a indicação da consorciação do fosfato de Patos de Minas com outro fosfato de qualidade superior.

Vitamin production in relation to phosphate solubilization by soil bacteria

Studies were conducted to determine the relationship of vitamin production and ability to dissolve bicalcium phosphate in bacteria isolated from rhizosphere, rhizoplane and control soil. Production of vitamin B 12, riboflavin, niacin, pantothenate and biotin was determined using a bioassay procedure that may be useful for large-scale screening of bacteria for vitamin production. Among isolates producing one or more vitamins, 76.4, 37.5 and 57.5% of control, rhizosphere and rhizoplane isolates, respectively, solubilized phosphate. However, phosphate-solubilizing isolates from rhizosphere and rhizoplane were more active vitamin producers than solubilizing isolates from control soil, and non-solubilizing isolates from any of the three regions. Production of vitamin B 12, riboflavin and niacin by rhizosphere isolates and of riboflavin by rhizoplane isolates was also correlated with ability to solubilize phosphate, but similar relationships were not observed for control isolates.