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Calcium-phosphate (CaP) ceramics have long occupied a central role in biomaterials science owing to their chemical similarity to bone mineral and favorable biological performance [...].Calcium-phosphate (CaP) ceramics have long occupied a central role in biomaterials science owing to their chemical similarity to bone mineral and favorable biological performance [...].

To prevent infections associated with medical implants, various antimicrobial silver-coated implant materials have been developed. However, these materials do not always provide consistent antibacterial effects in vivo despite having dramatic antibacterial effects in vitro, probably because the antibacterial effects involve silver-ion-mediated reactive oxygen species generation. Additionally, the silver application process often requires extremely high temperatures, which damage non-metal implant materials. We recently developed a bacteria-resistant coating consisting of hydroxyapatite film on which ionic silver is immobilized via inositol hexaphosphate chelation, using a series of immersion and drying steps performed at low heat. Here we applied this coating to a polymer, polyetheretherketone (PEEK), and analyzed the properties and antibacterial activity of the coated polymer in vitro and in vivo. The ionic silver coating demonstrated significant bactericidal activity and prevented bacterial biofilm formation in vitro. Bio-imaging of a soft tissue infection mouse model in which a silver-coated PEEK plate was implanted revealed a dramatic absence of bacterial signals 10 days after inoculation. These animals also showed a strong reduction in histological features of infection, compared to the control animals. This innovative coating can be applied to complex structures for clinical use, and could prevent infections associated with a variety of plastic implants.

Bacterial infection of biomaterials is a serious problem in the field of medical devices. It is urgently necessary to develop new biomaterials with bactericidal activity. Antimicrobial peptides and proteins (AMPs), alternative antibacterial agents, are expected to overcome the bacterial resistance. The aim of this study was to develop a new intelligent material in bone tissue engineering based on protamine-loaded hydroxyapatite (protamine/HAp) that uses AMPs rather than antibiotics. It was found that the adsorption of protamine to HAp followed the Langmuir adsorption model and was due to electrostatic and/or hydrophobic interactions. In vitro bacterial adhesion and growth on protamine/HAp was inhibited in a protamine dose-dependent manner. Adherent bacteria exhibited an aberrant morphology for high dosages of protamine/HAp, resulting in the formation of large aggregates and disintegration of the membrane. The released protamine from protamine/HAp also prevented the growth of planktonic bacteria in vitro. However, a high dosage of protamine from powders at loading concentrations over 1000 μg·mL−1 induced a cytotoxic effect in vitro, although those exhibited no apparent cytotoxicity in vivo. These data revealed that protamine/HAp (less than 1000 μg·mL−1) had both antimicrobial activity and biocompatibility and can be applied for bone substitutes in orthopedic fields.

Immunotherapy without side effects has been expected as a novel medical treatment for cancer. However, drugs such as cytokines typically used for immunotherapy are very expensive. Therefore, we propose the concept of immunoceramics that affect the immune system. Previous studies have shown that polymers including the phenylboronic acid group activate lymphocytes. This activation may be due to interaction between the sugar chains in cells and the OH group in B(OH)3 formed via dissociation of the BO2 group. In the present study, boron-containing apatite (BAp; Ca9.5+0.5x{(PO4)6−x(BO3)x}{(BO2)1–xOx} (0 ≤ x ≤ 1)) was successfully fabricated via the ultrasonic spray-pyrolysis (USSP) route. We examined the material properties of the BAp ceramics with an aim to application as immunoceramics and the responses of immune cells to the BAp ceramics. The crystalline phases of the BAp ceramics included the apatite phase and infrared (IR) absorption of BO2 and BO3 groups was detected in the BAp ceramics. The cellular response of immune cells derived from mice spleens to dense BAp ceramics was examined next. The proportion of helper T cells and killer T cells on BAp (x = 0.4) ceramics increased compared to that on hydroxyapatite (Ca10(PO4)6(OH)2; HAp) ceramics and on a control. These results indicate that BAp (x = 0.4) ceramics fabricated via the USSP route can be expected to act as immunoceramics that can affect the immune system.

In this study, the mechanism of fragmentation including void formation in an injectable calcium-phosphate cement of paste-like artificial bone grafting material, is clarified from the point of view of mathematical modeling. Instead of modeling from physical laws or chemical reactions, phenomenological modeling is used, and three experiments are performed to build the model. We then successfully use the results in terms of the equations and necessary assumptions to construct a simple mathematical model. Our proposed model is based on the mathematically well-known Allen-Cahn type equation. The state of the paste is used as an unknown function. After scaling according to the appropriate nondimensionalization, numerical simulations are performed. The numerical results represent the setting behavior of the paste, which is difficult to observe experimentally. The integration of mathematical and experimental results provides deep insight into the mechanism of non-fragmentation property of an injectable calcium-phosphate cement.

Calcium phosphates are key biomaterials in dental treatment and bone regeneration. Biomaterials must exhibit antibacterial properties to prevent microbial infection in implantation frameworks. Previously, we developed various types of calcium phosphate powders (amorphous calcium phosphate, octacalcium phosphate (OCP), dicalcium phosphate anhydrate, and hydroxyapatite) with adsorbed protamine (which is a protein with antibacterial property) and confirmed their antibacterial property. In this study, as foundational research for the development of novel oral care materials, we synthesized calcium phosphate composite powders from three starting materials: i) OCP, which intercalates organic compounds, ii) protamine, which has antibacterial properties, and iii) F– ion, which promotes the formation of apatite crystals. Through investigating the preparation concentration of the F– ions and their loading into OCP, it was found that more F– ion could be loaded at higher concentrations regardless of the loading method. It was also observed that the higher the preparation concentration, the more the OCP converted to fluorapatite. The synthesized calcium phosphate composite powders were evaluated for biocompatibility through proliferation of MG-63 cells, with none of the powders exhibiting any growth inhibition. Antimicrobial tests showed that the calcium phosphate composite powders synthesized with protamine and F– ion by precipitation had enhanced antimicrobial properties than those synthesized by protamine adsorption. Thus, the calcium phosphate composite powder prepared from OCP, protamine, and F– ion forms the basis for promising antimicrobial biomaterials.

Bacterial adhesion to the calcium phosphate surface is a serious problem in surgery. To prevent bacterial infection, the development of calcium-phosphate cements (CPCs) with bactericidal properties is indispensable. The aim of this study was to fabricate antibacterial CPCs and evaluate their biological properties. Silver-containing tricalcium phosphate (Ag-TCP) microspheres consisting of α/β-TCP phases were synthesized by an ultrasonic spray-pyrolysis technique. The powders prepared were mixed with the setting liquid to fabricate the CPCs. The resulting cements consisting of β-TCP and hydroxyapatite had a porous structure and wash-out resistance. Additionally, silver and calcium ions could be released into the culture medium from Ag-TCP cements for a long time accompanied by the dissolution of TCP. These data showed the bioresorbability of the Ag-TCP cement. In vitro antibacterial evaluation demonstrated that both released and immobilized silver suppressed the growth of bacteria and prevented bacterial adhesion to the surface of CPCs. Furthermore, histological evaluation by implantation of Ag-TCP cements into rabbit tibiae exhibited abundant bone apposition on the cement without inflammatory responses. These results showed that Ag-TCP cement has a good antibacterial property and good biocompatibility. The present Ag-TCP cements are promising for bone tissue engineering and may be used as antibacterial biomaterials.

The proportion of older people in the world's total population is expected to increase. Bone diseases are more prevalent in older people; therefore, the number of patients with such diseases is expected to increase worldwide. Artificial bone is a biomaterial used in the treatment of bone diseases. Artificial bones with high bone formation rates are desired; however, the results of artificial bone implantation vary. There are also ethical issues associated with animal experiments. Our purpose in this study is to predict the variation in bone formation rates. We created multiple sub‐datasets and constructed a machine learning model to predict the variation in bone formation rates by considering the results of multiple measurements. We also propose a metric, Jensen–Shannon (JS) divergence, to evaluate the accuracy of the model for predicting variation. We tested the validity of JS divergence by comparing combinations of explanatory variables. Additionally, we found an optimal combination of explanatory variables to construct a model with high predictive accuracy. We expect that the prediction of variation will be useful for improving the practical development of materials and medicines, such as artificial bones, for which stable effects are required, regardless of the individual.

To understand which properties of wet gels decide whether they can be dried under ambient pressure or not, the author prepared fifty-six gels from solutions of different mass ratios of tetra-functional tetramethoxysilane (TMOS), tri-functional methyltrimethoxysilane (MTMS) and difunctional dimethyldimethoxysilane (DMDMS). These gels were dried under ambient pressure, and the mechanical properties of the wet gels were investigated by uniaxial compression test. The stress-strain curve of the wet gels was composed of two parts (the 1st and 2nd parts) with different slopes. When the ratio of the 1st and 2nd parts ( E 2nd / E 1st , EM ratio) exceeded 2.3, the gel was dried without crack accompanying spring-back to obtain a dried gel with bulk density lower than 0.2 g/cm 2 . This finding means that the elastic modulus of a wet gel is a good criterion to predict whether or not they can be dried under ambient pressure without cracking to obtain a xerogel whose properties are close to the aerogel counterpart. Choosing a starting composition from fifty-six formulas, which gives the highest EM ratio, the author obtained a crack-free and transparent aerogel monolith with the dimension of 300 × 300 × 8 mm 3 through ambient pressure drying. 300 × 300 × 8 mm 3 aerogel monolith with 81% light-transmittance under ambient pressure drying. Highlights Aerogels were obtained from three-component system; TMOS, MTMS and DMDMS. While MTMS formed the main network, TMOS improved transparency and DMDMS affected elastic moduli of the gel. A 300 × 300 × 8 mm 3 crack-free aerogel monolith was obtained under ambient pressure drying. Elastic modulus of the wet gel was an important factor for successful ambient pressure drying.

With the limitation of autografts, the development of alternative treatments for bone diseases to alleviate autograft-related complications is highly demanded. In this study, a tissue-engineered bone was formed by culturing rat bone marrow cells (RBMCs) onto porous apatite-fiber scaffolds (AFSs) with three-dimensional (3D) interconnected pores using a radial-flow bioreactor (RFB). Using the optimized flow rate, the effect of different culturing periods on the development of tissue-engineered bone was investigated. The 3D cell culture using RFB was performed for 0, 1 or 2 weeks in a standard medium followed by 0, 1 or 2 weeks in a differentiation medium. Osteoblast differentiation in the tissue-engineered bone was examined by alkaline phosphatase (ALP) and osteocalcin (OC) assays. Furthermore, the tissue-engineered bone was histologically examined by hematoxylin and eosin and alizarin red S stains. We found that the ALP activity and OC content of calcified cells tended to increase with the culture period, and the differentiation of tissue-engineered bone could be controlled by varying the culture period. In addition, the employment of RFB and AFSs provided a favorable 3D environment for cell growth and differentiation. Overall, these results provide valuable insights into the design of tissue-engineered bone for clinical applications.