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Bioactive ceramics have been attractive because they spontaneously bond to living bone when implanted in bony defect. However, they are much more brittle and much less flexible than natural bone. Organic-inorganic hybrids consisting of flexible organic polymers and the essential constituents of the bioactive ceramics are useful as novel bone substitutes, owing to mechanical properties analogous to those of natural bone. In the present study, organic-inorganic hybrids were synthesized from 2-hydroxyethylmethacrylate (HEMA) by modification with Si-OH groups and Ca 2+ ions, which are effective constituents on the apatite formation. Bioactivity of the synthesized hybrids are estimated by examining ability of the apatite deposition in simulated body fluid (Kokubo solution). The prepared hybrids formed apatite in Kokubo solution within 1 d, when they were modified with appropriate amount of methacryloxypropyltrimethoxysilane (MPS) and CaCl 2 . Addition of glycerol 10 mol% to the hybrids as a plasticizer did not appreciably decrease their apatite-forming ability. These results show a potential of obtaining novel bone substitutes with high bioactivity and high flexibility.

Problems with poly(methylmethacrylate) (PMMA) bone cement arise owing to loosening between the bone and the cement after a long implantation period, due to a lack of bone-bonding ability, i.e. bioactivity. Bone-like apatite formation in the body environment is needed for an artificial material to show bioactivity. The silanol (Si–OH) group and calcium ions are effective components for inducing apatite nucleation. Organic–inorganic hybrids prepared by organic modification of these components have attracted much attention as novel bonerepairing materials having both bioactivity and flexibility like natural bone. We attempted to prepare bioactive PMMA cement by chemical modification based on the Organic–inorganic hybrids. Specifically, we added alkoxysilane and water-soluble calcium salts to the cements. The cement formed an apatite layer in simulated body fluid, which reproduces the body environment well, when the type of calcium salt was appropriately selected.

Artificial joints such as hip joint and knee joint have been popularly used for replacementofdamaged joints. To achieve a successful outcome offixation of the joints, surroundingbone tissues should have sufficient bone density. However bone density of elderlypatients is generally lower than that ofhealthy people due to diseases such as osteoporosis.This also makes it difficult to tightly fix the artificial joints to the bone. Thereforerecovery of the bone density is the important factor that governs success on theimplantation ofthe artificial joints. As a treatment to increase bone density ofthe patients,injectable bioactive filler with bone-bonding ability, Le. osteconductivity, can be anattractive candidate, since the osteoporosis can be recovered with minimal invasion. Sucha filler material should have not only osteoconductive property but also bioresorbabilityafter implantation in the bone tissue. It is known that osteoconduction on bioactive _materials is achieved by formation of biologically active hydroxyapatite (so-calledbone-like apatite) layer on their surfaces through chemical reaction with surroundingbody fluid. Heterogeneous nucleation of the hydroxyapatite is triggered by a catalyticeffect of specific functional groups on the material surfaces. In addition, release of Ca2+ions into the surrounding body fluids allows to enhance the apatite nucleation byincreasing degree of supersaturation with respect to the apatite. In this study, weattempted to develop injectable bioactive filler started from polyglutamic acid (pGA)through chemical cross-linkage, since PGA is abundant in carboxyl group that iseffective for inducing the apatite nucleation in body environments. The cross-linkage leadPGA hydrogel, whereas PGA without cross-linkage easily dissolved in aqueous media.The potential of the bone-like apatite formation was examined on the PGA gels due toexposure to a simulated body fluid (SBF) proposed by Kokubo and his colleagues. Aftersoaking in SBF for 7 days, trace amounts of particles were formed on the PGA gel, butwere not identified to bone-like apatite with X-ray diffraction. Formation of bone-likeapatite layer could be detected with X-ray diffraction on the PGAgels treated with CaChaqueous solution of 0.01 moldm-3 or more, followed by soaking in SBF for 7 days. Therate ofapatite formation increases with increasing concentration ofthe CaCh in the priortreatment. These results indicate that chemically cross-linked PGA gel has a potential toinduce the heterogeneous nucleation ofhydroxyapatite in body environment, and that thepotential would be remarkably enhanced by prior treatment ofthe gel with CaCh aqueoussolution.

Tolvaptan is an orally effective nonpeptide arginine vasopressin (AVP) V(2)-receptor antagonist synthesized by Otsuka Pharmaceutical Co., Ltd. In in vitro receptor-binding studies, tolvaptan blocked the binding of [(3)H]AVP to human V(2) receptors with 29-fold greater selectivity than that for V(1a) receptors, and showed no inhibition of V(1b) receptors. Tolvaptan inhibited not only the binding of [(3)H]AVP but also the AVP-induced production of cyclic AMP in human V(2)-receptor-expressing HeLa cells. In addition, tolvaptan has no intrinsic V(2) receptor agonistic effect. In in vivo studies, tolvaptan showed marked aquaresis in healthy and diseased animals. In rat models with acute and chronic hyponatremia, tolvaptan improved hyponatremia, resulting in the prevention of death, and improved organ water retention. Tolvaptan reduced cardiac preload without unfavorable effects on renal functions, systemic hemodynamics, or circulating neurohormones in dogs with heart failure (HF). Furthermore, in animal models of human polycystic kidney disease (PKD), tolvaptan showed a decrease in kidney weight as well as in cyst and fibrosis volume. In clinical trials including the "ACTIV in CHF" study, tolvaptan in addition to standard therapy increased fluid loss resulting in decreased body weight, and improved edema and serum sodium without affecting blood pressure, heart rate, or renal functions in patients with HF. In patients with hyponatremia, treatment with tolvaptan without fluid restriction appeared to be more effective than fluid restriction alone at correcting hyponatremia without an increase in adverse events. A phase III trial EVEREST is currently being conducted to evaluate the long-term efficacy and safety of tolvaptan in hospitalized patients with severe HF. In conclusion, tolvaptan offers the possibility of a useful therapy in hyponatremia, congestive heart failure, and various other diseases that are associated with volume overload. Furthermore, tolvaptan is also expected to be effective in the treatment of PKD.

Polymethylmethacrylate (PMMA)-based bone cement is used for the fixation of artificial joints in orthopaedics. However, the fixation is liable to loosen in the body, because the cement does not bond to living bone. So-called bioactive ceramics bond directly to living bone through the apatite layer formed on their surfaces in the body. We previously revealed that modification using gamma-methacryloxypropyltrimethoxysilane (MPS) and water-soluble calcium salts such as calcium acetate and calcium hydroxide was effective for providing the PMMA-based bone cement with apatite-forming ability in a simulated body fluid (SBF, Kokubo solution) that closely reproduces the body environment. However, the effect of the chemical reaction forming the apatite on the mechanical properties of the cements has not been clarified. The present work aimed to investigate this issue from the viewpoint of the interface structure between the apatite and the cement. The surface of the cement modified with calcium acetate and MPS was fully covered with newly formed apatite after soaking in Kokubo solution within 7 days, while half of the surface area of the cement modified with calcium hydroxide and MPS was covered with the apatite. The bending strength of the modified cements decreased after soaking in Kokubo solution. Porous structure was observed in the region about 50-100 microm in depth from the top surface because of release of the Ca2+ ions by both modified cements after soaking in Kokubo solution. The decrease in bending strength of the modified cements could be attributed to the formation of the pores. In addition, the pores on the top surfaces of the cements were filled with the newly formed apatite. The apatite formation would be effective not only for bioactivity but also for decreasing the reduction of mechanical strength.

Acidic proteins play an important role during mineral formation in biological systems, but the mechanism of mineral formation is far from understood. In this paper, we report on the relationship between the structure of a protein and hydroxyapatite deposition under biomimetic conditions. Sericin, a type of silk protein, was adopted as a suitable protein for studying structural effect on hydroxyapatite deposition, since it forms a hydroxyapatite layer on its surface in a metastable calcium phosphate solution, and its structure has been reported. Sericin effectively induced hydroxyapatite nucleation when it has high molecular weight and a β sheet structure. This indicates that the specific structure of a protein can effectively induce heterogeneous nucleation of hydroxyapatite in a biomimetic solution, i.e. a metastable calcium phosphate solution. This finding is useful in understanding biomineralization, as well as for the design of organic polymers that can effectively induce hydroxyapatite nucleation.

The therapeutic efficacy of tolvaptan (OPC-41061), a potent, selective nonpeptide vasopressin V2 receptor antagonist, on acute and chronic severe hyponatremia was assessed in rats. Experiments were designed to demonstrate the efficacy of tolvaptan reducing mortality in an acute model, and controlling the extent of serum sodium elevation without causing abnormal animal behavior suggesting neurological symptoms in a chronic model. In the acute model, rats developed rapidly progressive, severe hyponatremia by continuous sc infusion of [deamino-Cys1, d-Arg8]-vasopressin (10 ng/h) and forced water-loading (additional 10% initial body weight per day). By d 6, untreated rats had a 47% mortality rate. However, rats treated with repeated oral administrations of tolvaptan (1, 3, and 10 mg/kg) produced dose-dependent aquaresis (i.e. urine volume increased and urine osmolality decreased) that resulted in a gradual increase in plasma sodium concentration. Consequently, tolvaptan treatment reduced mortality and, at higher doses, resulted in no observed deaths. In the gradual model, rats receiving a continuous sc infusion of [deamino-Cys1, d-Arg8]-vasopressin (1 ng/h) combined with a liquid diet were induced to stable, severe hyponatremia (∼110 mEq/liter), which lead to increased organ weight and water content. Rats receiving dose titrations of tolvaptan (0.25, 0.5, 1, 2, 4, and 8 mg/kg) increased plasma sodium to healthy levels without causing abnormal animal behavior suggesting neurological symptoms or death, improved hyponatremia-driven increases in wet weight and water content in the organs. Thus, in animal models, analogous to the hyponatremia forms seen in humans, tolvaptan presents exciting therapeutic implications in the management of patients with severe hyponatremia.

Tricalcium phosphate (TCP) ceramic is known in orthopedics to be a bioresorbable bone substitute. A porous TCP ceramic body also has high potential as a drug delivery system in bony defects. Porous alpha-TCP ceramic can be easily fabricated using conventional sintering of beta-TCP, since alpha-TCP is the thermodynamically stable phase at temperatures above 1 100 degrees C. However, the solubility of alpha-TCP is much higher than that of beta-TCP. Therefore, the dissolution of porous alpha-TCP progresses at a higher rate than bone repair. In the present study, we attempted to reduce the dissolution rate of porous alpha-TCP by employing an organic polymer coating. We fabricated porous alpha-TCP ceramic with a continuous 10-50 microm diameter pore structure by sintering a body made from a beta-TCP and potato starch slurry. The porous body obtained was coated with hydroxypropylcellulose (HPC), and then subjected to heat treatment. The chemical durability and mechanical properties of the body were examined before and after coating with the HPC. The dissolution of porous alpha-TCP in buffered solutions was reduced by coating with HPC and drying at 60 degrees C. The compressive strength of the porous alpha-TCP was also improved by coating with HPC. The results of in vivo experiments showed that some parts of the porous alpha-TCP ceramic coated with HPC remained in the canal of the tibia of a rabbit four weeks after implantation, whereas no residual was observed in a non-coated alpha-TCP ceramic. Coating with HPC was found to be effective for controlling bioresorption and improving the workability of porous alpha-TCP ceramic. The prepared porous alpha-TCP ceramic is expected to be useful as a novel material for bone fillers by incorporating it with drugs or osteoinductive factors.

Hybrids consisting of bone-like apatite and biodegradable polymers are attractive materials for bone repair. We have shown that an alginate gel crosslinked covalently with ethylenediamine (EDA) enhances the repair of skin and nerves. In this study, we report a novel method for fabrication of an apatite-alginate nanohybrid using a simulated body fluid (SBF). Alginate was reacted with 3-aminopropyltriethoxysilane (APES), which gives silanol groups after hydrolysis, and/or EDA, by dehydration condensation using water-soluble carbodiimide to form gels. Modification of alginate with APES alone also gave a gel, because the alginate could be crosslinked by dehydration of silanol groups derived from APES. The gels obtained were soaked in a 1 mol/L CaCl2 solution and subsequently soaked in SBF. Apatite was formed on and inside the alginate gels modified with APES, whereas it was not formed on the gels without APES. Modification of alginate with silanol groups induced not only gel formation but also the apatite-forming ability on and inside the alginate gel in SBF. Consequently, a hydroxyapatite-alginate hybrid can be produced by modification of alginate with silanol groups and subsequent soaking in CaCl2 solution and SBF. Such a material is expected to be useful in bone repair.

The development of organic-inorganic hybrids composed of hydroxyapatite and organic polymers is attractive because of their novelty in being materials that show a bone-bonding ability, i.e. bioactivity, and because they have mechanical properties similar to those of natural bone. The biomimetic process has received much attention for fabricating such a hybrid, where bone-like apatite is deposited under ambient conditions on polymer substrates in a simulated body fluid (SBF) having ion concentrations nearly equal to those of human extracellular fluid or related solutions. It has been shown that the carboxyl group is effective for inducing heterogeneous nucleation of apatite in the body. In the present study, apatite deposition on polyamide films containing various numbers of carboxyl groups was investigated in 1.5 SBF, which had ion concentrations 1.5 times those of a normal SBF. The effect of incorporation of calcium chloride on the formation of apatite was examined. Polyamide films containingor=33 mol % CaCl(2) did not form apatite, even after soaking in 1.5 SBF for 7 days, and even when the polymer film contained 50 mol % carboxyl group. On the other hand, those modified withor=40 mass % CaCl(2) formed apatite on their surfaces in 1.5 SBF. The ability of the modified film to form an apatite layer increased, and the adhesion of the apatite layer bonded to the film improved, with increasing carboxyl group content. It is concluded that novel apatite-polyamide hybrids can be prepared by a biomimetic process.

So-called bioactive ceramics have been attractive because they form bone-like apatite on their surfaces to bond directly to living bone when implanted in bony defects. However, they are much more brittle and much less flexible than natural bone. Organic-inorganic hybrids consisting of flexible organic polymers and the essential constituents of the bioactive ceramics (i.e., Si-OH groups and Ca2+ ions) are useful as novel bone substitutes, because of their bioactivity and mechanical properties analogous to those of natural bone. In the present study, organic-inorganic nanohybrids were synthesized from hydroxyethylmethacrylate (HEMA) and methacryloxypropyltrimethoxysilane (MPS), as well as various calcium salts. Bioactivity of the synthesized hybrids was assessed in vitro by examining their acceptance of apatite deposition in simulated body fluid (Kokubo solution). The prepared hybrids formed apatite in Kokubo solution when they were modified with calcium chloride (CaCl2) at 5 or 10 mol% of the total of MPS and HEMA. Deposition of a kind of calcium phosphate was observed for the hybrids modified with calcium acetate (Ca(CH3COO)2), although it could not be identified with apatite. The addition of glycerol up to 10 mol% of the total of MPS and HEMA or water up to 20 mol% as plasticizers did not appreciably decrease the acceptance of apatite formation of the hybrids. These findings allow wide selectivity in the design of bioactive nanohybrids developed by organic modification of the Si-OH group and calcium ion through sol-gel processing. Such nanohybrids have potential as novel bone substitutes with both high bioactivity and high flexibility.

This paper develops a damage model for the evaluation of low cycle fatigue lives under complex cyclic multiaxial loadings. One of the authors has proposed the equivalent strain parameter for the life prediction of the nonproportional low cycle fatigue. This strain parameter can evaluate the dependence of fatigue lives on strain history and material, and correlates the fatigue lives within a small scatter band for 15 kinds of proportional and nonproportional strain paths. However, the parameter was only applicable to the life prediction under a limited nonproportional strain history, so that some modifications were required. In this study, a simple damage model for the life prediction is proposed by combining the equivalent strain parameter with Miner's law in order to apply it to the life prediction under more complex nonproportional loadings. The applicability of the proposed model is examined for the life evaluation of nonproportional low cycle fatigue for different materials; type 304 stainless steels, copper, aluminum alloys, chromium-molybdenum and carbon steels, which were obtained from different research institutes. The model can correlate most of the fatigue data within a factor of two scatter band and has a potential to become a good damage model for nonproportional low cycle fatigue.

Development of tantalum metal with bone-bonding ability is paid much attention because of its attractive features such as high fracture toughness, high workability and its achievement on clinical usage. Formation of bonelike apatite is an essential prerequisite for artificial materials to make direct bond to living bone. The apatite formation can be assessed in vitro using a simulated body fluid (SBF) that has almost equal compositions of inorganic ions to human blood plasma. The present authors previously showed that the apatite formation on tantalum metal in SBF was remarkably accelerated by treatment with NaOH aqueous solution and subsequent firing at 300 degrees C, while untreated tantalum metal spontaneously forms the apatite after a long soaking period. The purpose of the present study is to clarify the reason why the NaOH and heat treatments accelerate the apatite formation on tantalum metal. X-ray photoelectron spectroscopy was used to analyze changes in surface structure of the tantalum metal at an initial stage after immersion in SBF. Untreated tantalum metal had tantalum oxide passive layer on its surface, while amorphous sodium tantalate was formed on the surface of the tantalum metal by the NaOH and heat treatments. After soaking in SBF, the untreated tantalum metal sluggishly formed small amount of Ta-OH groups by a hydration of the tantalum oxide passive layer on its surface. In contrast, the treated tantalum metal rapidly formed Ta-OH groups by exchange of Na+ ion in the amorphous sodium tantalate on its surface with H3O+ ion in SBF. Both the formed Ta-OH groups combined with Ca2+ ion to form a kind of calcium tantalate, and then with phosphate ion, followed by combination with large amount of Ca2+ ions and phosphate ions to build up apatite layer. The formation rate of Ta-OH groups on the treated tantalum metal predominates the following process including adsorption of Ca2+ ion and phosphate ion on the surface. It is concluded that the acceleration of the apatite nucleation on the tantalum metal in SBF by the NaOH and heat treatments was attributed to the fast formation of Ta-OH group, followed by combination of the Ta-OH groups with Ca2+ and phosphate ions.

Untreated tantalum metal formed an apatite on its surface in simulated body fluid (SBF) with ion concentrations nearly equal to those of human blood plasma. However, it took an induction period as long as 4 weeks for apatite formation. The tantalum metal formed the apatite within 1 week when it was previously soaked in a 0.2 or 0.5M NaOH aqueous solution at 60 degrees C for 24 h to form a sodium tantalate hydrogel layer on its surface. The decrease in the induction period of apatite formation was attributed to the catalytic effect of the Ta-OH groups on the surface of the tantalum metal for apatite nucleation and acceleration of the apatite nucleation by an increased ionic activity product of the apatite in the fluid due to the release of Na(+) ions. The NaOH-treated tantalum metal can form apatite in a short period even in the living body and bond to the bone through this apatite layer. This indicates that a highly bioactive tantalum metal can be obtained by a simple chemical treatment.

Radiotherapy is a novel, non-invasive cancer treatment. Radioactive hollow microspheres, i.e., microcapsules, are attractive for in situ cancer radiotherapy because they can effectively reach tumors without settling in blood vessels. In particular, microcapsules 20-30 μm in size are expected to exhibit not only a radiotherapy effect but also embolization that blocks the nutrient supply to cancer cells. β-ray irradiation is the most suitable source for in situ radiotherapy because of its moderate range. Several kinds of β-emitting yttria (Y2O3) microcapsules have therefore been developed. Yttrium phosphate (YPO4) should have a longer irradiation effect than that of Y2O3 because the half-life of 31p (14.3 days) is longer than that of 90Y (64 .1 hours). However, the preparation of YPO4 microcapsules has not been reported to date. In the present study, YPO4 microcapsules were fabricated using a water/oil (W/O) emulsion prepared by first dispersing a YPO4 sol into toluene containing a surfactant, with mechanical homogenization. The emulsion was then added into butanol to dehydrate the water phase and precipitate microcapsules. These were then heat-treated to improve their mechanical strength and chemical stability. Microcapsule fragility at low YPO4 sol concentrations in the water phase was attributed to the thinness of the microcapsule shell. The size of the microcapsules decreased with increasing emulsification speed. The chemical stability of the prepared microcapsules is similar to those of previously reported YPO4 and Y2O3 microspheres in weakly acidic conditions. Thus, little leakage of radioactive species into nearby healthy tissues is expected. The obtained microcapsules are expected to be highly effective for cancer radiotherapy.

Chemically durable microspheres containing yttrium and/or phosphorus are useful for intra-arterial radiotherapy. In the present study, we attempted to prepare yttrium phosphate (YPO4) microspheres with high chemical durability as well as smooth surface and investigated their chemical durability in simulated body environment. YPO4 microspheres with smooth surface around 25 μm were successfully obtained, when gelatin droplets containing YPO4 precursor was cooled to be solidified in water-in-oil emulsion and then heat-treated at 1100°C. The chemical durability of the heat-treated microspheres in simulated body fluid at pH =6 and 7 was high enough for clinical application of radioembolic therapy of cancer.

Hydrogels able to form a bone-like hydroxyapatite (HAp) layer in the body environment are attractive materials as scaffolds for tissue engineering because they show osteoconductivity, i.e. bone-bonding property. In the present study, we synthesized hydrogels from sodium carboxymethylcellulose (sCMC), a water soluble polymer, through modification with a cross-linking agent, either ethylenediamine (EDA) or 3-aminopropyltriethoxysilane (APTES), followed by treatment with an aqueous solution containing calcium chloride aqueous solution. Formation of the bone-like HAp on the hydrogels was evaluated after immersion in a simulated body fluid (SBF). Hydrogels modified with the cross-linking agents EDA or APTES, and treated with 0.1 mol/dm3 of calcium chloride aqueous solution, formed a bone-like HAp layer on their surfaces after immersion in SBF for 3 days. Modification of organic polymers rich in carboxyl groups with APTES and CaCl2 offers a new method to produce biomaterials with greater potential for forming HAp, which provides high affinity to living bone because the incorporation of silanol groups confers the high ability to induce HAp formation.

Paste-like materials with ability of self-setting are attractive for bone substitutes, since they can be injected from the small hole with minimized invasion to the patient. Although bone cements which set as apatite are clinically used, there is limitation on clinical applications due to their mechanical properties such as high brittleness and low fracture toughness. To overcome this problem, organic-inorganic hybrids based on a flexible polymer are attractive. We have obtained an idea for design of self-setting hybrids using polyion complex fabricated by ionic interaction of anionic and cationic polymers. We aimed at preparation of organic-inorganic hybrids exhibiting self-setting ability and bioactivity. The liquid component was prepared from cationic chitosan aqueous solution. The powder component was prepared by mixing various carrageenans with α-tricalcium phosphate (α-TCP). The obtained cements set within 1 day. Compressive strength showed tendency to increase with increase in α-TCP content in the powder component. The prepared cements formed the apatite in simulated body fluid within 3 days. Novel self-setting materials based on organic-inorganic hybrid can be designed utilizing ionic interaction of polysaccharide.

Radiotherapy using ceramic microparticles that act as β-emitters after neutron bombardment is attractive as a minimally invasive option for cancer treatment. Yttria (Y2O3) microcapsules (20–30 µm in diameter) are capable of cutting off the nutrition supply in cancer cells through an embolization effect. In the present study, Y2O3 microcapsules were prepared via precipitation of yttrium hydroxide from a water/oil (W/O) emulsion and a subsequent heat treatment. The emulsion was prepared by dispersing yttrium hydroxide sol in 2-ethyl-1-hexanol. Microcapsules were obtained by an addition of the emulsion in butanol via dehydration and subsequent aggregation of the yttrium hydroxide. The effects of the rotation speed and surfactant concentration on the diameter of the particles were investigated. The diameter of the microcapsules showed a tendency to decrease with increases in rotation speed during emulsion preparation or surfactant concentration in the oil phase. A high yield of the Y2O3 microcapsules with a diameter of 20–30 µm were obtained after a heat treatment at the optimized rotation speed and surfactant concentration. The obtained microcapsules showed high chemical durability in a simulated body environment.

Several kinds of ceramics called bioactive ceramics have attractive features such as direct bone-bonding in living body. However, they are much more brittle and much less flexible than natural bone. Previous studies reported that the essential condition for materials to show bone-bonding property, i.e., bioactivity, is formation of biologically active apatite on their surfaces after exposure to the body fluid. The same type of apatite formation can be observed even in a simulated body fluid (SBF, Kokubo solution) with inorganic ion concentrations similar to those of human extracellular fluid. Several functional groups such as Si-OH and Ti-OH are known to trigger nucleation of the apatite in body environment. This is significantly enhanced by the release of Ca 2+ from the materials. These findings suggest that organic modification of bioactive inorganic components would provide bioactive materials with mechanical performances analogous to those of natural bone. We previously synthesized bioactive organic-inorganic hybrids from alkoxysilane that provides Si-OH groups and calcium salts that release Ca 2+ by organic modification with hydroxyethylmethacrylate (HEMA). If another type of functional group can be incorporated into the hybrids, useful guideline for designing bioactive materials with different biological and mechanical properties would be obtained. In this study, we synthesized organic-inorganic hybrids from HEMA by addition of tetraisopropyl titanate (TiPT) and CaCl 2 . Their apatite-forming ability was examined in SBF. The obtained hybrids formed the apatite in SBF within 7 d, when they were added with appropriate amount of CaCl 2 . It was speculated that the apatite deposition was induced by Ti-OH groups formed on the hybrids and the release of Ca 2+ . The chemicovectors including the ion release govern the apatite formation on the hybrids. Mechanical properties of the hybrids were also evaluated by tensile test. They showed Young's modulus analogous to human articular cartilage.

Chitosan microspheres can address challenges associated with poor bioavailability or unsustained drug release when used as drug delivery systems thanks to their mucoadhesiveness, which allows the drug dosage to be retained in the gastrointestinal track for extended periods. Chitosan-3-glycidoxypropyltrimethoxysilane-β-glycerophosphate (chitosan-GPTMS-β-GP) hybrid microspheres were synthetized through sol-gel processing using a microfluidic approach. Microspheres with uniform spherical shapes and sizes of approximately 650 μm were obtained. The microstructures of the microspheres consisted of four different siloxane structures. The degradation behaviors of the hybrid microspheres were examined under acidic pH conditions mimicking those found in the gastrointestinal track. Microspheres with different GPTMS molar ratios were incubated under several pH conditions for 2 weeks. The microspheres incubated at pH 7.4 extended the lowest weight loss (27%–32%), whereas those incubated at pH 1.7 and pH 5.4 showed greater weight losses of 43–59% and 69–77%, respectively. The inhibition of the degradation at low pH was dependent on the siloxane network in the chitosan matrix. Phosphate was mostly released in early stages, and the released amount of silicon was dependent on the composition. GPTMS was released with a chitosan chain via the hydrolysis of a chitosan molecule. The pelargonidin was incorporated in the microspheres and the slow releasing was observed at acidic condition. The resistance of these hybrid microspheres to low-pH conditions for longer than a full digestion cycle is promising for gastrointestinal drug delivery applications.