Release kinetics of ampicillin, characterization and bioactivity of TiO2/PCL hybrid materials synthesized by sol-gel processing

Poly(epsilon-caprolactone) (PCL 6, 12, and 24 wt %) and titanium (TiO2) organic-inorganic hybrid materials have been synthesized by the sol-gel method from a multicomponent solution containing titanium butoxide, poly(epsilon-caprolactone) (PCL), water, and chloroform (CHCl3). Sodium ampicillin was incorporated in the hybrid material to verify the effect as local controlled drug delivery system. The structure of a hybrid materials interpenetrating network is realized by hydrogen bonds between Ti-OH group (H-donator) in the sol-gel intermediate species and carboxylic group (H-acceptor) in the repeating units of the polymer. The presence of hydrogen bonds between organic/inorganic components of the hybrid materials was proved by FTIR analysis. The morphology of the hybrid materials was studied by scanning electron microscope (SEM). The structure of a molecular level dispersion has been disclosed by atomic force microscope (AFM), pore size distribution and surface measurements. The bioactivity of the synthesized hybrid materials has been showed by the formation of a layer of hydroxyapatite on the surface of TiO2/PCL samples soaked in a fluid simulating the composition of the human blood plasma. The amount of sodium ampicillin released has been detected by UV-vis spectroscopy and SEM. The release kinetics seems to occur in more than one stage. HPLC analysis has also been taken to ensure the integrity of ampicillin after the synthetic treatment.     

Effects of polymer amount and processing conditions on the in vitro behaviour of hybrid titanium dioxide/polycaprolactone composites

Titanium dioxide (TiO(2)) and TiO(2) glasses containing poly(epsilon-caprolactone) (PCL) up to 24% by weight were obtained by the sol-gel process. Powder compaction was achieved providing heat and pressure. Properties were evaluated through compression and bending tests assisted by X-ray micro-computed tomography imaging. The effects of compaction conditions (i.e. temperature, pressure and duration) on mechanical properties of inorganic/organic composites were investigated. Biocompatibility tests on organic/inorganic composites were carried out using human cells and the MTT assay to determine viability. Results indicated that the mechanical properties (i.e. Young's modulus and maximum strength), in both compression and bending, were a function of the compression moulding conditions. Highest mechanical properties were measured using a compaction pressure of 1500 MPa acting for 90 min at a die temperature of 100 degrees C. The results, however, also suggest that mechanical properties can be tailored by varying the amount of PCL to TiO(2). Strength and stiffness spanned between the properties of spongy and cortical bone. Young's modulus in both compression and bending were higher for PCL amounts of 6%. Instead, higher bending strength values were measured for PCL amounts of 12%. These weight amounts of PCL also provide higher average density values, thus suggesting that the polymeric phase is effective in toughening TiO(2)-based materials. The investigated materials also showed a very good cytocompatibility as indicated by the MTT assay results.     

The Comparison of the Ringed Spherulite Morphology of PCL Blends with Poly(vinyl chloride), Poly(bisphenol A carbonate) and Poly(hydroxyether of bisphenol A)

The crystallization and ringed spherulite morphology of poly(ε‐caprolactone) (PCL) in the miscible blends of PCL/poly(vinyl chloride) (PVC), PCL/poly(hydroxyether of bisphenol A) (phenoxy resin) and PCL/poly(bisphenol A carbonate) (PC) were investigated by differential scanning calorimetry (DSC) and polarized light microscopy (PLM). Through the comparison of the PCL crystalline morphology with the interaction energy density B between the miscible components in these blends, it was found that the addition of the non‐crystallizable component had great effect on the regularity of the ringed spherulite, which was coincided with the change of the interaction energy density B. To grow regular ringed spherulites in the PCL miscible blends, it was most important that the crystallization rate of PCL in the blends must be matched with the diffusion rate of the non‐crystallizable component. Such a matching relation in the process of the ringed spherulite growth was a most important condition for the regular twisting of PCL lamellae.     

Biomedical nanocomposites of hydroxyapatite/polycaprolactone obtained by surfactant mediation

The composite approach to combining bioactive ceramic and degradable polymer is a promising strategy in the development of bone regenerative matrices. Moreover, in the fabrication of composites, the nanoscale organization of each component should improve the level of structural integration as well as the resultant mechanical and biological properties. The aim of this study was to develop a novel nanocomposite system consisting of hydroxyapatite (HA) and poly(epsilon-caprolactone) (PCL), wherein the HA nanoparticles were uniformly dispersed within the PCL matrix. The strategy was based on applying an amphiphilic surfactant, oleic acid in this case, between the HA and PCL. Oleic acid, which belongs to the fatty acid family and is generally noncytotoxic at the levels used in this study, is believed to mediate the interaction between the hydrophilic HA and hydrophobic PCL. With the mediation of oleic acid, the HA nanoparticles were distributed uniformly within the PCL matrix on the nanoscale (distributed particle size of less than 1 microm), which is in marked contrast to the conventionally mixed HA-PCL composite, in which the HA particles were severely agglomerated. The developed nanocomposite had significantly higher mechanical strength than did the conventional composite and the pure PCL. Moreover, the osteoblastic cells showed a better proliferation behavior on the nanocomposite than on the conventional composite. This HA-PCL nanocomposite mediated by oleic acid is expected to be useful in the bone regeneration field. Moreover, this methodology is applicable to the nanocomposite processing of other biomedical materials.     

Biodegradable polymer nanocomposites: the role of nanoclays on the thermomechanical characteristics and the electrospun fibrous structure

Polymer nanocomposites, based on poly(e-caprolactone) (PCL) and organically modified montmorillonite, were prepared by the solution intercalation technique. The thermal stability of the prepared materials was analyzed by thermogravimetric analysis. Investigation of their mechanical properties revealed that incorporation of the high aspect ratio montmorillonite sheets into the matrix significantly enhanced the polymer stiffness without sacrificing its ductility. Fibrous membranes of neat and nanocomposite PCL were fabricated by electrospinning. The effect of the applied voltage, the solution concentration and the clay content of the nanocomposite materials on the final fibrous structure was investigated. The results showed that the introduction of the inorganic filler and the increase in the applied voltage from 7.5 to 15 kV facilitated the formation of fine fibers with fewer bead defects. The presence of nanoclay resulted in narrower fiber size distributions, although the mean fiber diameter was not significantly altered. The increase in the solution concentration led to the formation of more uniform fiber structures and to a slight increase in the mean fiber diameter. Furthermore, the electrospinning process affected significantly the structure of the nanocomposite material by increasing the interlayer spacing of the inorganic mineral.     

LCST phase separation in biodegradable polymer blends: poly(D,L‐lactide) and poly(ϵ‐caprolactone)

A lower critical solution temperature (LCST) phase transition is reported for blends of the biodegradable polymers poly(D,L ‐lactide) (PDLA) and poly(ε‐caprolactone) (PCL). From light scattering measurements the cloud point curve is determined to have a critical temperature of 86°C and a critical concentration of mass fraction 36 wt.‐% PCL. Optical microscopy of phase‐separated films indicates a spinodal morphology at the critical concentration, and droplet phases at off‐critical concentrations. After quenching phase separated blends below the melting temperature of PCL (60°C), the crystallization of PCL is used to positively identify PCL‐rich and PDLA‐rich phases. When cystallization of PCL follows LCST phase separation, the size, shape, and distribution of crystalline regions can be adjusted by the degree of PCL/PDLA phase separation. Thus, the LCST phase separation offers a novel method to control microphase structure in biodegradable materials. Applications to control of mechanical and physical properties in tissue engineering scaffolds are discussed in light of the results.     

Biocomposites of non-crosslinked natural and synthetic polymers

Biocomposite films comprising a non-crosslinked, natural polymer (collagen) and a synthetic polymer, poly(epsilon-caprolactone) (PCL), have been produced by impregnation of lyophilised collagen mats with a solution of PCL in dichloromethane followed by solvent evaporation. This approach avoids the toxicity problems associated with chemical crosslinking. Distinct changes in film morphology, from continuous surface coating to open porous format, were achieved by variation of processing parameters such as collagen:PCL ratio and the weight of the starting lyophilised collagen mat. Collagenase digestion indicated that the collagen content of 1:4 and 1:8 collagen:PCL biocomposites was almost totally accessible for enzymatic digestion indicating a high degree of collagen exposure for interaction with other ECM proteins or cells contacting the biomaterial surface. Much reduced collagen exposure (around 50%) was measured for the 1:20 collagen:PCL materials. These findings were consistent with the SEM examination of collagen:PCL biocomposites which revealed a highly porous morphology for the 1:4 and 1:8 blends but virtually complete coverage of the collagen component by PCL in the 1:20 samples. Investigations of the attachment and spreading characteristics of human osteoblast (HOB) cells on PCL films and collagen:PCL materials respectively, indicated that HOB cells poorly recognised PCL but attachment and spreading were much improved on the biocomposites. The non-chemically crosslinked, collagen:PCL biocomposites described are expected to provide a useful addition to the range of biomaterials and matrix systems for tissue engineering.     

A Prerequisite of the Poly(ε‐Caprolactone) Self‐Induced Nanohybrid Shish–Kebab Structure Formation: An Ordered Crystal Lamellae Orientation Morphology of Fibers

The shish–kebab structure has been extensively applied in many fields; however, the formation mechanism is still an open question. In this study, different electrospun poly(ε‐caprolactone) (PCL) fibers are applied as the shish material in a self‐induced crystallization process, and two different self‐induced crystal structures are obtained. The PCL fibers with an ordered crystalline morphology lead to an induced crystalline structure with the crystal lamellae perpendicular to the fiber axis. However, the PCL fibers with a disordered structure induce a complicated (less ordered) crystalline lamellae morphology. Investigation of the surface crystalline structure reveals that the self‐induced nanohybrid shish–kebab (SINSK) structure follows a lattice matching and epitaxial growth mechanism. The internal crystalline structure of PCL nanofibers plays a dominant role in the formation of the SINSK structure. This study may prove helpful in screening materials for formation of the SINSK structure.     

Bioactive poly(2-hydroxyethylmethacrylate)/silica gel hybrid nanocomposites prepared by sol-gel process

A hybrid of poly(2-hydroxyethylmethacrylate) (pHEMA), a polymer widely employed for biomedical applications, and silica gel, exhibiting a well-known bioactivity, was produced by sol-gel. The amount of the inorganic precursor, tetraethoxysilane (TEOS), was mixed to the organic monomer, so as to have a final concentration of 30% (w/w) of silica gel to the mass of polymer. The nanocomposite was characterized for its composition by thermogravimetric (TG) analysis, swelling behavior, glass transition temperature using differential thermal analysis (DTA), morphology through scanning electron microscopy (SEM), and bioactivity using FT-IR spectroscopy, SEM, and energy dispersive system (EDS). The nanocomposite showed phase separation between the polymer and the silica gel, improved thermal stability and swelling properties and higher glass transition temperature than pHEMA. Moreover, bioactive SiO(2) gel nanoparticles promoted apatite formation on the surface of the modified hydrogel, when it was soaked in SBF. Therefore, the obtained bioactive nanocomposite can be used to make bioactive scaffold for bone engineering.     

Ternary Thermosetting Blends of Epoxy Resin,Poly(ethylene oxide) and Poly(ε‐caprolactone)

Summary: The ternary thermosetting blends composed of epoxy resin, poly(ethylene oxide) (PEO) and poly(ε‐caprolactone) (PCL) were prepared via in situ polymerization of epoxy monomers in the presence of the two crystalline polymers, PEO and PCL. DSC results showed that the binary blends of epoxy with PEO (and/or PCL) are fully miscible in the entire composition in the amorphous state. FTIR indicates that there were interchain specific interactions between the crosslinked epoxy and the linear polymers in the binary blends and the hydrogen bonding interactions between epoxy and PCL are much weaker than those between epoxy and PEO. The difference in the strength of interchain specific interactions gives rise to the competitive hydrogen bonding interactions in the ternary blends of epoxy, PEO and PCL, which were evidenced by the results of FTIR. The results of optical microscopy and DSC showed that in the ternary blends PCL component separated out with inclusion of PEO. The formation of the specific phase structures is ascribed to the competitive interchain specific interactions among the crosslinked epoxy, PEO and PCL.

Phase boundary diagram of epoxy, PEO and PCL ternary blends.     

Biphenyl liquid crystalline epoxy resin as a low-shrinkage resin-based dental restorative nanocomposite

Low-shrinkage resin-based photocurable liquid crystalline epoxy nanocomposite has been investigated with regard to its application as a dental restoration material. The nanocomposite consists of an organic matrix and an inorganic reinforcing filler. The organic matrix is made of liquid crystalline biphenyl epoxy resin (BP), an epoxy resin consisting of cyclohexylmethyl-3,4-epoxycyclohexanecarboxylate (ECH), the photoinitiator 4-octylphenyl phenyliodonium hexafluoroantimonate and the photosensitizer champhorquinone. The inorganic filler is silica nanoparticles (～70–100 nm). The nanoparticles were modified by an epoxy silane of γ-glycidoxypropyltrimethoxysilane to be compatible with the organic matrix and to chemically bond with the organic matrix after photo curing. By incorporating the BP liquid crystalline (LC) epoxy resin into conventional ECH epoxy resin, the nanocomposite has improved hardness, flexural modulus, water absorption and coefficient of thermal expansion. Although the incorporation of silica filler may dilute the reinforcing effect of crystalline BP, a high silica filler content (～42 vol.%) was found to increase the physical and chemical properties of the nanocomposite due to the formation of unique microstructures. The microstructure of nanoparticle embedded layers was observed in the nanocomposite using scanning and transmission electron microscopy. This unique microstructure indicates that the crystalline BP and nanoparticles support each other and result in outstanding mechanical properties. The crystalline BP in the LC epoxy resin-based nanocomposite was partially melted during exothermic photopolymerization, and the resin expanded via an order-to-disorder transition. Thus, the post-gelation shrinkage of the LC epoxy resin-based nanocomposite is greatly reduced, ～50.6% less than in commercialized methacrylate resin-based composites. This LC epoxy nanocomposite demonstrates good physical and chemical properties and good biocompatibility, comparable to commercialized composites. The results indicate that this novel LC nanocomposite is worthy of development and has potential for further applications in clinical dentistry.     

Titania-hydroxyapatite nanocomposite coatings support human mesenchymal stem cells osteogenic differentiation

In addition to mechanical and chemical stability, the third design goal of the ideal bone-implant coating is the ability to support osteogenic differentiation of mesenchymal stem cells (MSCs). Plasma-sprayed TiO(2)-based bone-implant coatings exhibit excellent long-term mechanical properties, but their applications in bone implants are limited by their bioinertness. We have successfully produced a TiO(2) nanostructured (grain size <50 nm) based coating charged with 10% wt hydroxyapatite (TiO(2)-HA) sprayed by high-velocity oxy-fuel. On Ti64 substrates, the novel TiO(2)-HA coating bond 153× stronger and has a cohesive strength 4× higher than HA coatings. The HA micro- and nano-sized particles covering the TiO(2)-HA coating surface are chemically bound to the TiO(2) coating matrix, producing chemically stable coatings under high mechanical solicitations. In this study, we elucidated the TiO(2)-HA nanocomposite coating surface chemistry, and in vitro osteoinductive potential by culturing human MSCs (hMSCs) in basal and in osteogenic medium (hMSC-ob). We assessed the following hMSCs and hMSC-ob parameters over a 3-week period: (i) proliferation; (ii) cytoskeleton organization and cell-substrate adhesion; (iii) coating-cellular interaction morphology and growth; and (iv) cellular mineralization. The TiO(2) -HA nanocomposite coatings demonstrated 3× higher hydrophilicity than HA coatings, a TiO(2)-nanostructured surface in addition to the chemically bound HA micron- and nano-sized rod to the surface. hMSCs and hMSC-ob demonstrated increased proliferation and osteoblastic differentiation on the nanostructured TiO(2)-HA coatings, suggesting the TiO(2)-HA coatings nanostructure surface properties induce osteogenic differentiation of hMSC and support hMSC-ob osteogenic potential better than our current golden standard HA coating.     

The Study of Miscibility and Hydrogen Bonding in Blends of Phenolics with Poly(ε‐caprolactone)

Blends of phenolics with poly(ε‐caprolactone) (PCL) were prepared by solution casting from the tetrahydrofuran (THF) solution. Differential scanning calorimetry (DSC) and Fourier‐Transform infrared spectroscopy (FTIR) were used to examine the miscibility behavior and hydrogen bonding of the blend. This phenolics/PCL blend system is fully miscible based on single glass transition temperature due to the formation of inter hydrogen bonding between hydroxyl of phenolic and carbonyl of PCL. In addition, a negative polymer‐polymer interaction energy density “B” was obtained based on the melting depression of PCL using the Nishi‐Wang equation. Furthermore, FTIR was used to study the hydrogen‐bonding interaction between the phenolic hydroxyl group and the PCL carbonyl group at various temperatures and compositions. Moreover, the inter‐association equilibrium constant and its related enthalpy of phenolic/PCL blends were determined and used to predict the miscibility window, free energy and fraction of the hydrogen bonding according to the Painter‐Coleman association model (PCAM).     

Thermosetting Blends of Polybenzoxazine and Poly(ε‐caprolactone): Phase Behavior and Intermolecular Specific Interactions

Summary: Polybenzoxazine (PBA‐a)/poly(ε‐caprolactone) (PCL) blends were prepared by an in situ curing reaction of benzoxazine (BA‐a) in the presence of PCL. Before curing, the benzoxazine (BA‐a)/PCL blends are miscible, which was evidenced by the behaviors of single and composition‐dependant glass transition temperature and equilibrium melting point depression. However, the phase separation induced by polymerization was observed after curing at elevated temperature. It was expected that after curing, the PBA‐a/PCL blends would be miscible since the phenolic hydroxyls in the PBA‐a molecular backbone have the potential to form intermolecular hydrogen‐bonding interactions with the carbonyls of PCL and thus would fulfil the miscibility of the blends. The resulting morphology of the blends prompted an investigation of the status of association between PBA‐a and PCL under the curing conditions. Although Fourier‐transform infrared spectroscopy (FT‐IR) showed that there were intermolecular hydrogen‐bonding interactions between PBA‐a and PCL at room temperature, especially for the PCL‐rich blends, the results of variable temperature FT‐IR spectroscopy by the model compound indicate that the phenolic hydroxyl groups could not form efficient intermolecular hydrogen‐bonding interactions at elevated temperatures, i.e., the phenolic hydroxyl groups existed mainly in the non‐associated form in the system during curing. The results are valuable to understand the effect of curing temperature on the resulting morphology of the thermosetting blends.

SEM micrograph of the dichloromethane‐etched fracture surface of a 90:10 PBA‐a/PCL blend showing a heterogeneous morphology.     

Influence of the microstructure and topography on the barrier properties of oxide scales generated on blasted Ti6Al4V surfaces

The long-term interfacial bond between an implant and bone may be improved by creating a rough surface on the implant in order to increase the surface area available for bone/implant apposition. A natural consequence of surface roughening is an increase in metal ion release, which is itself a surface dominated process. Based on this fact, the aim of this work is to study the influence of the microstructure and topography on the barrier properties of oxide scales thermally generated at 700 °C for 1h on Ti6Al4V surfaces after blasting with Al(2)O(3) particles (coarse) or SiO(2) and ZrO(2) particles (fine). The microstructural and topographical characterization of the thermally treated blasted surfaces has been studied by means of scanning electron microscopy coupled with energy dispersive X-ray analysis, contact profilometry and X-ray diffraction. The barrier properties and corrosion behaviour of the oxide layers have been studied by means of electrochemical impedance spectroscopy (EIS) in Hank's solution. Thermal treatment at 700 °C for 1h promotes the formation of oxide scales with different morphologies and crystalline structures depending on the degree of deformation of the blasted surface. The oxide scale grown on the finely blasted sample has a pine needle-like morphology which is mainly formed of anatase TiO(2). In contrast, the oxide scale grown on the coarsely blasted sample has a globular morphology formed mainly of rutile TiO(2). The differences in morphology, i.e. fine or coarse, of the oxide scales influence the corrosion response of the blasted thermally treated samples in Hank's solution. The EIS results permit evaluation of the different oxide scales from the capacitance and resistance values obtained in the high-frequency region and show a good correlation between the morphology and barrier properties. Oxidation treatment at 700 °C for 1h of Ti6Al4V samples coarsely blasted with Al(2)O(3) improves the corrosion behaviour due to an increase in the thickness of a compact, ordered and more structurally stable oxide scale. This is due to the globular morphology of the rutile (TiO(2)) structure maintaining an average surface roughness suitable for optimal osseo-integration with long-term interfacial bonding between the implant and bone.     

Covalent attachment of a three-dimensionally printed thermoplast to a gelatin hydrogel for mechanically enhanced cartilage constructs

Hydrogels can provide a suitable environment for tissue formation by embedded cells, which makes them suitable for applications in regenerative medicine. However, hydrogels possess only limited mechanical strength, and must therefore be reinforced for applications in load-bearing conditions. In most approaches the reinforcing component and the hydrogel network have poor interactions and the synergetic effect of both materials on the mechanical properties is not effective. Therefore, in the present study, a thermoplastic polymer blend of poly(hydroxymethylglycolide-co-ε-caprolactone)/poly(ε-caprolactone) (pHMGCL/PCL) was functionalized with methacrylate groups (pMHMGCL/PCL) and covalently grafted to gelatin methacrylamide (gelMA) hydrogel through photopolymerization. The grafting resulted in an at least fivefold increase in interface-binding strength between the hydrogel and the thermoplastic polymer material. GelMA constructs were reinforced with three-dimensionally printed pHMGCL/PCL and pMHMGCL/PCL scaffolds and tested in a model for a focal articular cartilage defect. In this model, covalent bonds at the interface of the two materials resulted in constructs with an improved resistance to repeated axial and rotational forces. Moreover, chondrocytes embedded within the constructs were able to form cartilage-specific matrix both in vitro and in vivo. Thus, by grafting the interface of different materials, stronger hybrid cartilage constructs can be engineered.     

电纺丝PLLA/HA复合纤维支架的制备及体外降解性能研究

随着组织工程和支架材料的技术发展，复合支架材料的制备成为当前研究的热点。本研究通过静电纺丝法制备了左旋聚乳酸／羟基磷灰石（PLLA／HA）复合纳米纤维膜，对纤维膜的结构形态进行分析，并研究其在与人体环境相近的磷酸盐缓冲溶液（pH7．4，37℃）中浸泡不同时间的体外降解过程。结果表明：HA纳米粒子与PLLA基体间存在化学键合，纳米粒子使纤维直径增大且表面粗糙程度增加，HA的引入抑制了PLLA降解过程中的自催化作用，减缓了PLLA的降解速度，复合纤维体系降解液的pH值在降解后期呈缓慢上升趋势。     

PCL基复合骨组织工程支架研究现状及发展

三维骨组织工程支架已成为成骨研究领域的热点。聚己内酯(PCL)具有良好的生物相容性,在骨组织工程研究中被广泛应用于三维支架的制备。但纯PCL支架亲水性差、生物活性低,限制了其在生物医学领域的应用。随着骨组织工程材料研究的发展,大量研究者将PCL与各种无机物、金属元素或胶原等活性材料进行复合,以改善支架性能或引入新的性能。针对PCL基骨组织工程复合支架的材料选择,从PCL复合无机材料、PCL复合水凝胶材料、PCL复合金属元素、PCL复合小分子药物以及PCL复合生物活性分子等5个方面,对各类复合支架的性能及体内外成骨效果等方面进行综述,希望对PCL在骨组织工程中的研究及临床应用提供一定的帮助。     

Hydroxylapatite and titanium: interfacial reactions

The chemical reactions between hydroxylapatite (HA) and titanium were studied in three different kinds of experiments to increase understanding of how to bond HA to titanium for implant materials. HA powder was bonded to a titanium rod with hot isostatic pressing. Interdiffusion of the HA elements and titanium was found in concentration profiles measured in the electron microprobe. Titanium was vapor-deposited on sintered HA discs and heated in air; perovskite (CaTiO(3)) was found on the HA surface with Rutherford backscattering and X-ray diffraction measurements. Powder composites of HA and titanium and TiO(2) were sintered at 1100 degrees C; again, perovskite was a reaction product, as well as beta-Ca(3)(PO(4))(2), from decomposition of the HA. These results demonstrate chemical reactions and interdiffusion between HA and TiO(2) during sintering, resulting in chemical bonding between HA and titanium. Thus, cracks and weakness at HA-titanium interfaces probably result from mismatch between the coefficients of thermal expansion of these materials. HA composites with other ceramics and different alloys should lead to better thermal matching and better bonding at the interface.     

Apatite-forming ability and mechanical properties of PTMO-modified CaO-SiO2-TiO2 hybrids derived from sol-gel processing

Hydrolysis and polycondensation of triethoxysilane end-capped Poly (tetramethylene oxide) (Si-PTMO), tetraethoxysilane (TEOS), tetraisopropyltitanate (TiPT) and calcium nitrate (Ca(NO(3))(2)) gave transparent monolithics of PTMO-modified CaO-SiO(2)-TiO(2) hybrids. The samples with (TiPT)/(TEOS+TiPT) molar ratios from 0 to 0.20 under constant ratio of (Si-PTMO)/(TEOS+TiPT) of 2/3 in weight were prepared. It was found that the incorporation of TiO(2) component into a PTMO-CaO-SiO(2) hybrid results in an increase in the apatite-forming ability in a simulated body fluid: the hybrids with (TiPT)/(TEOS+TiPT) of 0.10 and 0.20 in mol formed an apatite on their surfaces within only 0.5 day. It seemed that, within the range of compositions studied, the TiO(2) content little affects the overall mechanical properties: Young's modulus were 52-55MPa, tensile strength, 7-9MPa, and strain at failure, about 30%. Thus, the organic-inorganic hybrids exhibiting both fairly high apatite-forming ability and high capability for deformation were obtained. These hybrid materials may be useful as new kind of bioactive bone-repairing materials.