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Pulmonary pleomorphic carcinoma (PPC) is a rare type of non‐small cell lung cancer (NSCLC) with a more aggressive clinical course and a worse outcome than other types of NSCLC. Pembrolizumab, a monoclonal antibody targeting programmed cell death‐1 (PD‐1), has been approved as the first‐line treatment for advanced NSCLC with robust PD‐L1 expression in at least 50% of tumour cells, without epidermal growth factor receptor gene (EGFR) mutations or anaplastic lymphoma kinase gene (ALK) rearrangement. Here, we report the case of an 81‐year‐old man with multiple comorbidities who was diagnosed with PPC and showed a robust response to pembrolizumab followed by radiation therapy without adverse effects. In the absence of randomized clinical trials for PPCs, our case report demonstrates the potential application of pembrolizumab and radiation therapy for the treatment of PPCs., We report the case of an 81‐year‐old man with multiple comorbidities who was diagnosed with pulmonary pleomorphic carcinoma (PPC), a rare type of non‐small cell lung cancer (NSCLC) with a more aggressive clinical course and a worse outcome than other types of NSCLC. Our patient showed a robust response to pembrolizumab followed by radiation therapy without adverse effects. In the absence of randomized clinical trials for PPCs, our case report demonstrates the potential application of pembrolizumab and radiation therapy for the treatment of PPCs.

Neural stem cells (NSC) have tremendous potential for therapeutic regeneration of diseased or traumatized neural tissues, including injured spinal cord. However, transplanted NSC suffer from low cell survival and uncontrolled differentiation, limiting in vivo efficacy. Here, this issue is tackled by delivery through silk-collagen protein hydrogels that are stiffness-matched, stress-relaxing, and shear-thinning. The mechanically-tuned hydrogels protect NSC reprogrammed from fibroblasts (iNSC) initially from injection shear-stress, and enhance long-term survival over 12 weeks. Hydrogel-iNSC treatment alleviates neural inflammation, with reduced inflammatory cells and lesions than NSC-only. The iNSC migrate from the hydrogel into surrounding tissues, secrete up-regulated neurotrophic factors, and differentiate into neural cell subtypes, forming synapses. More serotonergic axons are observed in the lesion cavity, and locomotor functions are improved in hydrogel-iNSC than in iNSC-only. This study highlights the ability of mechanically-tuned protein hydrogels to protect iNSC from the injection stress and severe inflammatory environment, allowing them to differentiate and function to recover the injured spinal cord.

Aim This study was conducted in order to examine the effects of community-based education on cervical cancer prevention in relation to South Korean mothers’ knowledge about the Papanicolau (Pap) test and human papillomavirus, self-confidence in communication with their daughters, and health-related beliefs about their daughters. Methods A quasi-experimental pre–post design was used. For the experimental group, face-to-face education was administered to 35 participants for 60 min. For the control group, 35 participants were taught by using standardized materials for 20 min. Results The experimental group showed a significant increase in Pap test knowledge, cervical cancer knowledge, and self-confidence in communication with their daughters, compared to the control group. In the post-test, the mothers in the experimental group also perceived cervical cancer as more threatening, their daughter as more susceptible to cervical cancer, Pap tests as being recommended for their daughters, and they showed a significant increase in their self-efficacy of recommending the Pap test to their daughter. Conclusion Community-based education for mothers is effective in increasing their human papillomavirus knowledge, Pap test knowledge, improving their confidence in communication with their daughters, and in some of the health-related beliefs regarding their daughters.

Aims and objectives This study aimed to develop a nurse-led psychological intervention program and to evaluate its effects on psychological distress and quality of life in patients with breast cancer undergoing chemotherapy and at a high risk of depression. Background Depression is common among patients with breast cancer undergoing chemotherapy. Psychological intervention programs that improve psychological distress and quality of life have previously been lacking in South Korea. Design This was a pre- and post-test randomized controlled trial. Methods The nurse-led psychological intervention program comprised seven weekly counseling sessions delivered face-to-face and telephonically. These aimed to provide emotional support to patients and to enable them to express their feelings. Patients at a high risk of depression were recruited from an oncology outpatient clinic in a university hospital. Sixty participants were evenly and randomly allocated to either the intervention group or the control group. The effects of the intervention on psychological distress (mood disturbance, anxiety, and depression) and quality of life were examined using linear mixed models. Results Compared with the control group, the intervention group reported significantly lower mood disturbance, anxiety, and depression, and showed an improved global health status and physical, role, and emotional functions. They also reported fewer symptoms such as fatigue, nausea/vomiting, pain, and insomnia. Conclusions Our nurse-led psychological intervention program might reduce patients’ uncertainty and encourage them to be pro-active and self-controllable. Relevance to clinical practice Nurse-led psychological intervention programs should be implemented to reduce psychological distress and improve quality of life in patients with breast cancer, particularly those at a high risk of depression. This article is protected by copyright. All rights reserved.

Nanocarriers are one of the key elements to improve the therapeutic potential of signaling molecules, including genes for the disease treatment and tissue repair. Here, a nanocarrier system is reported that delivers genetic molecule small interference RNA (siRNA) for osteoblastic stimulation. For this, a hollow form of mesoporous silica nanoshell (MSns) is designed to load and release siRNA to silence Plekho-1 gene. In particular, a pressure-induced loading method is effective in enhancing the incorporation of siRNA within a hollow space; a loading level attained ≈30% is almost three times higher than that of a non-hollow form. Furthermore, the release of siRNA from the nanocarriers is highly sustainable; continued over 18 d in a diffusion-controlled manner, in striking contrast to the rapid release (3 d) from a non-hollow form. The nanocarriers exhibit excellent cell viability, and the siRNA-nanocarrier complexes are efficiently internalized to osteoblastic cells (uptake level over 90%). The intracellular delivery suppresses the target gene Plekho-1 expression down to 20%, which in turn up-regulates the expression of osteoblast transcriptional factors (Runx2 and Smad2), demonstrating an effective gene delivery system for bone repair.

The sustained release of growth factors following their implantation in vivo is essential for successful outcomes in bone tissue engineering. In this study, we evaluated the release kinetics and delivery efficacies of vascular endothelial growth factor (VEGF), a potent angiogenic growth factor, incorporated into calcium phosphate bone grafts (BGs). We evaluated the release profile of VEGF from BGs using a novel fluorescence-based retention assay, which revealed that VEGF loaded on BGs can be released in a sustained manner without an initial burst (near zero-order cumulative release) with a controlled release rate of 13.6% per week for up to 7 weeks. In contrast, an ELISA-based release assay showed VEGF to have an early burst-release profile for the first week. However, the biological activity of VEGF released from the BGs was preserved over the 7-week release period, which is consistent with the sustained-release profile observed in the fluorescence-based retention assay. Furthermore, the in vivo bone-forming action of the VEGF-loaded BGs was well demonstrated in a rat subcutaneous model. Taken together, the sustained release of VEGF loaded onto BGs was effective in stimulating proliferation, angiogenesis and osteogenesis, suggesting the ultimate value of VEGF-engineered BGs for bone tissue engineering.

Co-delivery strategy using multifunctional nanocarriers is an attractive option for the synergistic and enhanced effects in cancer treatment, but one system integrating multiple functions for controlled release at the target is still challenging. Herein, this study shows the synthesis and characterization of our stimulus-responsive co-delivery system for the controlled release into tumors, which is composed of polyethylenimine (PEI)-linked Pluronic F127 (PF127) and folic acid (FA), called PF127-PEI-FA. PF127-PEI-FA system facilitated drug loading and gene complex formation, and showed controlled release behaviors in response to hitting temperature to hyperthermia. PF127-PEI-FA system was demonstrated to be biocompatible and showed receptor-mediated gene delivery. The results of our multifunctional nanocarrier system that enabled co-delivery suggest a promising potential for controlled drug release at targeted areas. However, further in-depth studies on the use of therapeutic drugs and genes in multiple cell types and the animal response are required.

Summary Male breast cancers (MBC) are rare, accounting for

Insufficient integration with local host tissues is a significant problem that adversely affects the performance of implanted biomedical devices. Poor tissue integration leaves patients susceptible to complications associated with adverse foreign body reactions and infections that typically mandate expensive and elevated-risk revision surgery. The aging population and growing incidence of medical implants makes the development of bio-functional implant surfaces a high priority research imperative. Here multifunctional surfaces are reported that are capable of regulating cell adhesion and triggering cell differentiation to facilitate osseointegration of implantable devices. The approach described is universal, cost- and time-effective. It relies on a unique combination of two advances: i) a reactive interface provided by a plasma activated coating (PAC) that covalently immobilises bioactive molecules with significantly higher efficiency than conventional technologies, and ii) multifunctional molecules (bi-functional fusion-proteins) that regulate multiple cellular responses. Covalent linking of the molecules, their high density, and desired orientation are demonstrated. The effectiveness of these functional interfaces to regulate mesenchymal stem cell attachment and differentiation is confirmed suggesting the ability to regulate osseointegration. This method is a leap forward in the fabrication of truly biofunctional materials tailored for particular applications.

Development of biocompatible multifunctional nanocarriers is necessary for the success of theranostics. Here, we report a novel hybrid nanorod with self-fluorescent property, high drug loading capacity, and good biocompatibility. Fluorescent hydroxyapatite (fHA) nanorod was ensheathed with mesoporous silica (mSi). The mSi shell was uniformly layered and was tunable in thickness (10–30 nm) over the fHA nanorod. Highly mesoporous structure of mSi shell facilitated the loading of a large quantity of biological molecules, as confirmed with fluorescein isothiocynate; ~1% loading for fHA increased to ~10% loading for fHA@mSi. The self-fluorescent property of the fHA resulting from CO2.− radicals was well preserved in the fHA@mSi hybrid, as analyzed by photoluminescence and electron paramagnetic resonance property. Cellular toxicity of the fHA@mSi hybrid nanorod showed favorable cell viability (>90% viability of control) up to a concentration of ~40 μg/mL. Intracellular uptake rate of the hybrid nanorod was as high as 80–90%, as analyzed by fluorescent-assisted cell sorter. Results demonstrate the newly developed fHA@mSi nanocarriers have great potential for the effective loading of therapeutic molecules and delivery within intracellular compartments in concert with a capacity for in situ imaging.

Scaffolds with the capacity to deliver signaling molecules are attractive for bone regeneration. Here, we developed bioactive siloxane-gelatin hybrid scaffolds via a sol gel process containing stromal derived factor-1 (SDF-1) to recruit osteoprogenitor/stem cells. The process was undertaken under room temperature aqueous conditions, which enabled therapeutic molecules to be effectively incorporated. After the sol-gel reaction and lyophilization process, well-crosslinked hybrid scaffolds were obtained with porosities of 80-90%. Dynamic mechanical analysis of the hybrid scaffolds showed significant improvement in storage modulus values (from 10 to 110 kPa) with increasing siloxane content. The protein release capacity of the scaffolds was investigated using a model protein cytochrome C (cyto C). The cyto C safely loaded onto the scaffolds exhibited, except the initial burst of 30% within a day, highly sustainable release, with approximately 70-80% of the loading amount for up to 4 weeks. Target molecule SDF-1 was loaded and released from the scaffolds, and the effects on the homing of mesenchymal stem cell were studied. Results demonstrated significant enhancement in the migration of cells to the SDF-1 loaded scaffolds. Taken together, the developed hybrid scaffolds are considered to be useful in loading and delivering signaling molecules such as SDF-1 to recruit osteoprogenitor /mesenchymal stem cells in the bone regeneration process.

The sustained release of growth factors plays a critical role in therapeutic applications because of the instability of these factors in the body. Here, we designed a fibroblast growth factor 2 (FGF2) fused with a collagen-binding domain (rhCBD-FGF2) for collagen-based sustained release of FGF2.The release profile of rhCBD-FGF2 showed sustained release from collagen matrices. Further, rhCBD-FGF2 also stimulated adhesion of the MC3T3-E1 cells to the collagen matrices. In addition, rhCBD-FGF2 increased the cell proliferation activity at 3 and 5 days in the MC3T3-E1 cells attached to the collagen matrices compared to that in the control. Further, rhCBD-FGF2 significantly induced the osteogenic differentiation of MC3T3-E1 cells on collagen matrices by up-regulating the alkaline phosphatase activity at 7 days. These osteogenic differentiation activities were confirmed in gene expression of MC3T3-E1 cell. Taken together, rhCBD-FGF2 could specifically bind with collagen matrices, which indicates important advancements in bone tissue engineering.

We report the ability of aminated mesoporous silica nanoparticles (MSN–NH2) with large mesopore space and positive-charged surface to deliver genes within rat mesenchymal stem cells (MSCs). The amine functionalized inorganic nanoparticles were complexed with bone morphogenetic protein-2 (BMP2) plasmid DNA (pDNA) to study their transfection efficiency in MSCs. Intracellular uptake of the complex BMP2 pDNA/MSN–NH2 occurred significantly, with a transfection efficiency of approximately 68%. Furthermore, over 66% of the transfected cells produced BMP2 protein. The osteogenic differentiation of the transfected MSCs was demonstrated by the expression of bone-related genes and proteins including bone sialoprotein, osteopontin, and osteocalcin. The MSN–NH2 delivery vehicle for BMP2 pDNA developed in this study may be a potential gene delivery system for bone tissue regeneration. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

The functionalization of degradable polymeric scaffolds with therapeutic molecules such as vascular endothelial growth factor (VEGF) is a key strategy to gain better regenerative ability of damaged bone tissue by stimulating vascularization and tissue perfusion. Here, we combined VEGF with poly(lactic acid) (PLA) porous scaffold, after modifying the PLA surface with calcium phosphate (CaP) mineral. The mineralized PLA scaffold (mPLA) showed more effective loading capacity of VEGF than the PLA without mineralization as well as profiled sustainable release of VEGF for up to a couple of weeks. The VEGF-loaded mPLA scaffold presented significantly improved proliferation of primary endothelial cells for up to 7 days, with respect to the scaffold without the VEGF loading. The performance of the engineered scaffold was assessed after subcutaneous implantation in rats for 4 weeks. Histological results showed favorable tissue compatibility of both the mPLA scaffolds (with and without VEGF loading), as characterized by infiltration of inflammatory cells, formation of fibrous capsule, and ingrowth of fibroblasts into the matrices. Immunohistochemical staining of the von Willebrand Factor revealed significantly improved formation of neo-capillaries in the VEGF-loaded mPLA. Based on this study, the strategy of VEGF loading onto mineralized PLA scaffold is considered beneficial for gaining improved vascularization of the polymeric scaffolds, suggesting potential applications for bone tissue engineering.

Development of scaffolds to load and deliver therapeutic molecules like growth factors greatly enhances tissue regenerative capacity. Here, we report the core-shell design of fibrous scaffolds made of alginate and α-tricalcium phosphate (Alg/α-TCP) for in situ protein loading and controllable delivery. Direct deposition of Alg/α-TCP solution through designed coconcentric nozzle in CaCl(2) bath allowed the generation of fibrous scaffolds. Through the process, in situ protein loading was possible and the core and shell composition was controlled. Feasibility of the designed scaffolds in loading and release of biological model protein cytochrome C (cyt C) was investigated. Scaffolding formed in CaCl(2) led to a considerable loss of cyt C in a crosslinking time-dependent manner, and the change in hardening conditions (Alg concentration, CaCl(2) concentration, and Alg/α-TCP ratio) was not as effective in reducing the protein loss. Subsequent release of cyt C from Alg scaffolds displayed a marked initial burst depending on crosslinking conditions, and shortening crosslinking time and decreasing CaCl(2) concentration lowered the initial burst. The α-TCP addition (up to 75%) resulted in more continual and sustainable release patterns. Composition change (α-TCP content) in core or shell significantly altered the release profiles, suggesting the possible designing core-shell configuration for target release patterns, such as dual-protein delivery. Additionally, the α-TCP incorporation significantly increased the mechanical stiffness to values much closer to those of hard tissues. Results indicate that coaxial deposited α-TCP/Alg fibrous scaffolds may be useful for designing proper growth factor delivery systems in hard tissue engineering.

Herein, we developed a bioactive nanofibrous membrane by coating the bioactive glass nanofiber with degradable biopolymers, such as poly(caprolactone) and poly(lactic acid). A thin layer of the biopolymers could be covered on the glass nanofiber through a capillary-driven infiltration of the polymer solution into the small-sized nanofibrous mesh. The biopolymer-coated glass nanofiber showed significantly enhanced mechanical properties while preserving the excellent bioactivity of the glass nanofiber. The produced nanofibrous membrane may be useful as a bioactive substrate for defect-filling and cell-culturing in bone regeneration area.

Degradable polymer-based materials are attractive in orthopedics and dentistry as an alternative to metallic implants for use as bone fixatives. Herein, a degradable polymer poly(lactic acid) (PLA) was combined with novel hybrid nanopowder of carbon nanotubes (CNTs)-calcium phosphate (CP) for this application. In particular, CNTs-CP hybrid nanopowders (0.1 and 0.25% CNTs) were prepared from the solution of ionically modified CNTs (mCNTs), which was specifically synthesized to be well-dispersed and thus to effectively adsorb onto the CP nanoparticles. The mCNTs-CP hybrid nanopowders were then mixed with PLA (up to 50%) to produce mCNTs-CP-PLA nanocomposites. The mechanical tensile strength of the nanocomposites was significantly improved by the addition of mCNTs-CP hybrid nanopowders. Moreover, nanocomposites containing low concentration of mCNTs (0.1%) showed significantly stimulated biological responses including cell proliferation and osteoblastic differentiation in terms of gene and protein expressions. Based on this study, the addition of novel mCNT-CP hybrid nanopowders to PLA biopolymer may be considered a new material choice for developing hard tissue implants. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.

Self-hardening microspheres were developed as a 3-dimensional (3D) matrix for bone regeneration. α-tricalcium phosphate (α-TCP)-based calcium phosphate cement (CPC) was mixed with collagen and emulsified to produce spherical microparticulates, during which the spheres could be hardened within minutes. The immersion of the microspheres in a fluid allowed the transformation of the α-TCP into bone mineral-like hydroxyapatite. Biological protein could be easily encapsulated within the microspheres and was released in a sustained manner over a month. Bone cells were shown to adhere and grow actively upon the CPC-collagen microspheres. The newly developed CPC-collagen microspheres with self-hardening property may be potentially useful as a 3D matrix for bone regeneration.

Degradable polymer nanofibers produced by electrospinning are attractive for use in cell culture and tissue repair. However, the hydrophobicity and initial poor cell adhesion of synthetic polymers have limited their use in tissue regeneration. Herein, the surface of a poly(lactide-co-caprolactone) Arg-Gly-Asp sequence of nanofiber was tailored with a fibronectin peptide (FN10), which was designed to retain the central cell-binding domain. The electrospun nanofibers are first treated with an alkaline solution to reveal the carboxyl groups on the surface, which is followed by coupling with an FN10 solution in conjunction with a carbodiimide-based agent. Peptide coupling occurs effectively with saturation within 1 h, and the coupled peptide maintains its stability for several days. The peptide-coupled nanofibers show significant improvements in initial cell adhesion and spreading compared with the untreated one, confirming the role of the FN10 peptide in the initial cell events. This methodology may be useful in tailoring the surface of polymeric nanofibers with biomolecules targeted for specific tissue responses.

Bioactive and degradable composite microspheres (bioactive glass-synthetic biopolymer) were produced to deliver tissue cells and to aid their osteogenic development targeted for hard tissues. Cellular population (left, SEM cell image at day 3) and osteoblastic differentiation (right, immunofluorescence staining with bone marker at day 14) on the microspheres was evident, suggesting the composite microspheres provided effective 3D substrate conditions for hard tissue regeneration.

In this study, a poly(e-caprolactone) (PCL)/bioactive glass (BG) nanocomposite was fabricated using BG nanofibers (BGNFs) and compared with an established composite fabricated using microscale BG particles. The BGNFs were generated using sol–gel precursors via the electrospinning process, chopped into short fibers and then incorporated into the PCL organic matrix by dissolving them in a tetrahydrofuran solvent. The biological and mechanical properties of the PCL/BGNF composites were evaluated and compared with those of PCL/BG powder (BGP). Because the PCL/BG composite containing 20 wt % BG showed the highest level of alkaline phosphatase (ALP) activity, all evaluations were performed at this concentration except for that of the ALP activity itself. In vitro cell tests using the MC3T3 cell line demonstrated the enhanced biocompatibility of the PCL/BGNF composite compared with the PCL/BGP composite. Furthermore, the PCL/BGNF composite showed a significantly higher level of bioactivity compared with the PCL/BGP composite. In addition, the results of the in vivo animal experiments using Sprague–Dawley albino rats revealed the good bone regeneration capability of the PCL/BGNF composite when implanted in a calvarial bone defect. In the result of the tensile test, the stiffness of the PCL/BG composite was further increased when the BGNFs were incorporated. These results indicate that the PCL/BGNF composite has greater bioactivity and mechanical stability when compared with the PCL/BG composite and great potential as a bone regenerative material. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009

Heparin/heparan sulfate (HS) plays a key role in cellular adhesion. In this study, we utilized a 12-mer random Escherichia coli cell surface display library to identify the sequence, which binds to heparin. Isolated insert analysis revealed a novel heparin-binding peptide sequence, VRRSKHGARKDR, designated as HBP12. Our analysis of the sequence alignment of heparin-binding motifs known as the Cardin-Weintraub consensus (BBXB, where B is a basic residue) indicates that the HBP12 peptide sequence contains two consecutive heparin-binding motifs (i.e. RRSK and RKDR). SPR-based BIAcore technology demonstrated that the HBP12 peptide binds to heparin with high affinity (KD = 191 nM). The HBP12 peptide is found to bind the cell surface HS expressed by osteoblastic MC3T3 cells and promote HS-dependent cell adhesion. Moreover, the surface-immobilized HBP12 peptide on titanium substrates shows significant increases in the osteoblastic MC3T3-E1 cell adhesion and proliferation.

Degradable synthetic polymers with a nanofibrous structure have shown great promise in populating and recruiting cells for the reconstruction of damaged tissues. However, poor cell affinity and lack of bioactivity have limited their potential usefulness in bone regeneration. We produced polymeric nanofiber poly(e-caprolactone) (PCL) with its surface mineralized with bone-like apatite for use as bone regenerative and tissue engineering matrices. PCL was first electrospun into a nanofibrous web, and the surface was further mineralized with apatite following a series of solution treatments. The surface of the mineralized PCL nanofiber was observed to be almost fully covered with nanocrystalline apatites. Through mineralization, the wettability of the nanofiber matrix was greatly improved. Moreover, the murine-derived osteoblastic cells were shown to attach and grow actively on the apatite-mineralized nanofibrous substrate. In particular, the mineralized PCL nanofibrous substrate significantly stimulated the expression of bone-associated genes, including Runx2, collagen type I, alkaline phosphatase, and osteocalcin, when compared with the pure PCL nanofiber substrate without mineralization. The currently developed polymer nanofibrous web with the bioactive mineralized surface is considered to be potentially useful as bone regenerative and tissue engineering matrices. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009

Using the HF, MP2, and DFT methods with a 6-311G** basis set, we examine the internal-rotation and inversion of the amino and phosphino groups in methylamine and methylphosphine. The resulting energy surfaces are reported as a function of rotation and inversion descriptors. Both surfaces are characterized by several special points: three minimum energy states, three first-order internal-rotation transition states, six first-order inversion transition states, and six second-order inversion transition states. The MP2 method gave better agreement with experiment. For methylamine, the MP2 energy barrier for internal-rotation is 8.73 kJ/mol; for first-order inversion it is 22.80 kJ/mol and for second-order inversion it is 22.41 kJ/mol. For methylphosphine, the MP2 energy barriers are 7.53, 149.88, and 149.65 kJ/mol, respectively. The energy barriers include ZPE correction contributions. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2008

The objective of this study was to fabricate porous hydroxyapatite (HA) scaffolds coated with bioactive A/W glass–ceramics and to examine their mechanical and biological properties. Firstly, the HA scaffolds were prepared by the polymeric sponge replication method, and then A/W glasses were coated on the surface of the struts. All of the scaffolds had a highly porous structure with well-interconnected pores. It was observed that the bioactive glass coating markedly increased the strength of the HA scaffolds. This enhancement was attributed to the formation of a dense and strong coating layer on the weak HA struts. The in vitro bioactivities of the scaffolds were markedly improved by the coatings. When the coated scaffolds were soaked in a simulated body fluid (SBF), the bone-like apatite crystals were well mineralized on their surfaces. Osteoblast-like cells (MC3T3) adhered, spread, and grew well on the porous scaffolds. The cells placed on the glass-coated HA scaffold showed a higher proliferation rate and alkaline phosphatase (ALP) activity than those on the pure HA scaffold. These results demonstrate that the bioactive glass coating is effective in improving the strength and bioactivity of the porous HA scaffolds.

The alumina–zirconia (Al2O3–ZrO2) system is considered as one of the most useful nanocomposites, finding widespread applications in structural field. To provide optimal performance, the scale reduction of the initial powder or of the final grain morphology is of particular importance. To accomplish this, we developed a novel Al–Zr-oxide hybridized nanopowder using the Pechini-type sol–gel method. Within this process, we maintained a uniform distribution of the Al and Zr metallic ions, and kept these ions stable at the molecular distance level with the help of polymeric additives. The transmission electron spectroscopyanalysis of the nanopowder revealed that the individual particles were ultrastructured, with both Al-oxide and Zr-oxide regions being interspaced within 10 nanometers. The Al2O3–ZrO2 nanocomposite made from the hybridized nanopowder by a hot-pressing technique showed ultrafine grain morphology. Moreover, the mechanical strength of the nanocomposite measured by a four-point flexural test was as high as 1.5 GPa. The Al–Zr-oxide hybridized nanopowder and its nanocomposite developed herein are considered to find potential uses in engineering applications.

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.

A nano-sized hydroxyapatite (HA) layer was coated on a Ti substrate with a titanium oxide (TiO 2 ) buffer layer by the electron-beam deposition method. The morphological features as well as the mechanical and biological properties of the HA/ TiO 2 -layered coating were noticeably different from those of a conventional HA coating on Ti. The HA on the TiO 2 layer replicated the fine grain structure of the TiO 2 layer, with grain sizes of just a few tens of nanometers. The TiO 2 buffer layer was highly effective in preserving the adhesion strength of the coating layer following the heat treatment at 500°C, which was necessary to crystallize the structure. Moreover, in contrast to the HA single coating wherein severe cracking was observed under moist conditions, the HA/TiO 2 coating retained its mechanical stability under the same conditions. The dissolution of the HA/TiO 2 coating in a physiological saline solution exhibited a more favorable pattern than that of the HA single coating, with a reduced initial burst and a subsequent steady release rate. Preliminary in vitro cellular tests showed that osteoblastic cells expressed a significantly higher alkaline phosphatase level on the HA/TiO 2 coating than on the HA single coating. Conclusively, the nano-sized HA coating with the TiO 2 buffer layer holds great promise as a bioactive coating system.

We investigated the effect of polystyrene (PS) addition on the freezing behavior of a very dilute alumina/camphene slurry with an initial solid loading of 5 vol% for the fabrication of ultra-high porosity ceramics with aligned pore channels. To accomplish this, slurries with various PS contents (10, 20, and 30 vol% in relation to the alumina powders) were prepared by ball milling at 60°C and then cast into molds at a constant temperature of 20°C. After removing the frozen camphene, the samples were heat treated to burn out the organic phases and sinter the alumina walls. The addition of the PS binder remarkably enhanced the green strength of the sample, making it possible to handle it without difficulty. All of the sintered samples showed ultra-high porosities of >88% without the collapse of the porous structure, wherein the pore channels were completely interconnected. Three distinctive zones having different pore structures were observed, viz. the outer shell with elongated pores, the inner zone with long aligned pore channels, and the center with equiaxed pores. The content of the PS polymer significantly affected the pore morphologies in the three distinctive zones. In addition, it was found that the addition of the PS polymer was highly beneficial to the alignment of the pore channels.

Biomedical composites of hydroxyapatite (HA) and bioactive glass (BG) have been difficult to obtain as a dense body without the undesirable occurrence of thermal reactions and phase degradation. Herein, HA–BG dense composites were produced by the hot-pressing technique. A range of HA–BG powder mixtures (30–50 wt% BG) was fully densified by hot pressing at temperatures as low as ∼700°–800°C. On the other hand, the HA–BG composites could not be densified by pressureless sintering because their composition was degraded due to a severe thermal reaction. The hot-pressed composites had significantly improved flexural strengths (∼60 MPa) as compared with those subjected to pressureless sintering (∼30 MPa) or the pure HA control (∼40 MPa). The hot-pressed HA–BG composites showed significantly enhanced bioactivity in a simulated body fluid, as well as osteoblast cell activity with respect to the pure HA, confirming their excellent in vitro biocompatibility.

Over the past decades, bioactive glass has played a central role in the bone regeneration field, due to its excellent bioactivity, osteoconductivity, and even osteoinductivity. Herein, exploitation of bioactive glass as a one-dimensional nanoscale fiber by employing an electrospinning process based on a sol-gel precursor is reported for the first time. Under controlled processing conditions, continuous nanofibers have been generated successfully with variable diameters. The excellent bioactivity of the nanofiber is confirmed in vitro within a simulated body fluid by the rapid induction of bonelike minerals onto the nanofiber surface. The bone-marrow-derived cells are observed to attach and proliferate actively on the nanofiber mesh, and differentiate into osteoblastic cells with excellent osteogenic potential. The bioactive nanofibers have been further exploited in various forms, such as bundled filament, nanofibrous membrane, 3D macroporous scaffold, and nanocomposite with biopolymer, suggesting their versatility and potential applications in bone-tissue engineering. Based on this study, the bioactive nanofibrous matrix is regarded as a promising next-generation biomaterial in the bone-regeneration field.

A hydroxyapatite/fluorapatite (HA/FA) double layer was coated on ZrO2 by a powder slurry method. The FA layer between the HA layer and the ZrO2 substrate was effective in suppressing the reaction between HA and ZrO2. The rheological properties of the slurry and the thermal treatment conditions were optimized. Addition of small amounts of tri-ethyl phosphate dispersant and polyvinylbutyral binder (up to 5 wt%) was effective in reducing the slurry viscosity, even at high loadings of HA powder. Each layer (HA, FA) was deposited on ZrO2 repeatedly to induce a uniform layer, and the final heat treatment was carried out above 1200°C to consolidate the coating layer. During this process, without the FA-intermediate layer, a severe reaction between HA and ZrO2 occurred to form tri-calcium phosphate and CaZrO3 products. However, the presence of the FA layer between HA and ZrO2 effectively suppressed the reaction up to 1300°C. The obtained HA/FA double coating layer was micro-porous and relatively rough, but was firmly adhered to the ZrO2 substrate, having a bonding strength of approximately 25 MPa after heat treatment above 1200°C. The osteoblast-like cells cultured on the HA/FA coating layer spread and proliferated favorably, having a cell proliferation rate comparable to that of a plastic control and HA bulk ceramic.

This study was conducted to identify the potential relationship between the dietary intake level of soy isofla- vones and perimenstrual symptomatology. The research design was a cross-sectional study. The sample was made up of 84 Korean women living in the USA, aged 28-40 years. The Moos Menstrual Distress Question- naire (MDQ) and the Food Frequency Questionnaire were used as measurement tools. The soy isoflavone intake was significantly correlated with MDQ scores in the menstrual phase. In conclusion, the beneficial effect of dietary soy isoflavones on certain menstrual symptoms was established, suggesting that soy isofla- vones could be one of the dietary factors related to the complexity of premenstrual syndrome (PMS). The pos- itive effect of soy isoflavones on PMS warrants further study.

In this study, we produced hydroxyapatite (HA) and fluor-hydroxyapatite (FHA) bioceramics as a novel geometrical form, the nanoscale fiber, for the biomedical applications. Based on the sol-gel precursors of the apatites, an electrospinning technique was introduced to generate nanoscale fibers. The diameter of the fibers was exploited in the range of a few micrometers to hundreds of nanometers (1.55 microm-240 nm) by means of adjusting the concentration of the sols. Through the fluoridation of apatite, the solubility of the fiber was tailored and the fluorine ions were well released from the FHA. The HA and FHA nanofibers produced in this study are considered to find potential applications in the biomaterials and tissue engineering fields.

The biocompatibility of fluoridated apatite (FHA) was significantly improved by the addition of a resorbable phosphate-based glass. With the addition of small amounts of the glass (up to 5%) to the FHA, a completely densified body was obtained after sintering at 1250 C. The resultant crystalline phase was composed of tricalcium phosphate (TCP) and FHA. The addition of the glass to the FHA significantly improved the viability and functional activity of osteoblastic cells, while these were only slightly improved when the glass was added to pure hydroxyapatite, demonstrating that the fluoridation and glass addition had a synergistic stimulatory effect. This finding suggests that the glass-added FHA bioceramic would be highly useful as a hard tissue reconstructive material.

Nanoscale organized organic-inorganic nanocomposite systems have great potential in the development of biomaterials with advanced properties. Herein, we developed a novel nanocomposite biomaterial consisting of bioactive glass nanofiber (BGNF) and collagen reconstituted fibrous matrix for bone regenerative medicine. A sol-gel derived glass with a bioactive composition (58SiO(2). 38CaO.4P(2)O(5)) was electrospun to a nanoscale fiber with an average diameter of approximately 320 nm. The BGNF was subsequently hybridized with type I collagen, which is the main organic constituent of bone matrix. The BGNF and self-assembled collagen sol were combined in aqueous solution, and then crosslinked to produce a BGNF-collagen nanocomposite, in the form of either a thin membrane or a macroporous scaffold, by adopting appropriate processing conditions. The BGNF was observed to be distributed uniformly within the collagen reconstituted nanofibrous matrix. The nanocomposite matrices induced rapid formation of bone-like apatite minerals on their surfaces when incubated in a simulated body fluid, exhibiting excellent bioactivity in vitro. Osteoblastic cells showed favorable growth on the BGNF-collagen nanocomposite. In particular, the alkaline phosphatase activity of the cells on the nanocomposite was significantly higher than that on the collagen. This novel BGNF-collagen nanocomposite is believed to have significant potential in bone regeneration and tissue engineering applications.