Platelets are blood components traditionally believed to have fundamental roles in vascular hemostasis and thrombosis. In recent years, platelets have received new attention for their roles in tumorigenesis and progression. On the one hand, platelets are actively recruited by various tumors and comprise a crucial part of the tumor microenvironment (TME), thus inspiring the use of platelets for tumor-targeted drug delivery. To this end, various platelet-based devices have been proposed, such as natural platelets, engineered platelets, platelet membranes, and platelet-derived microparticles. On the other hand, platelets are involved in tumor immunosuppression mechanisms, by directing and/or assisting various tumor-associated immune cells. However, in the context of inflammation and autoimmune diseases, platelets can amplify immune responses by promoting immune cell mobilization and activation, thereby exacerbating tissue damage. Thus, interest is growing in the use of tumor-associated platelets as targets for therapeutic modulation of the TME and augmenting anti-tumor immune responses. In this review, we summarize current advances in exploiting platelets for both antitumor drug delivery and immune modulation of the TME.

Because of their excellent mechanical, electrical and biocompatible properties, multiwalled carbon nanotubes (MWCNTs) are employed for tissue engineering. Recent studies have also revealed that CNTs provide a preferable surface for cell adhesion and growth. Osteoblast-like cells adhere well and grow on the MWCNT-coated collagen sponge better than on the non-coated sponge. On the other hand, titanium is commonly used as a biomaterial for dental implants because of its excellent mechanical and biocompatible properties. Various surface modifications, e.g. anodization and apatite coating, are employed for current dental implants to achieve earlier osseointegration. The purpose of this study was to coat anodized titanium with MWCNTs (CNT-Ti) and investigate the effects of this successfully CNT-Ti on osteoconductivity. Human osteosarcoma cells, Saos2, were cultured on CNT-Ti discs. CNT-Ti wires were implanted in the bone marrow space in femurs of rats for 2 and 4 weeks, and histological and histomorphometric evaluations were carried out. The anodized Ti could be coated homogeneously with MWCNTs. Saos2 cells on CNT-Ti showed prompted proliferation.

Soft tissue engineering has been developed as a new strategy for repairing damaged or diseased soft tissues and organs to overcome the limitations of current therapies. Since most of soft tissues in the human body are usually supported by collagen fibers to form a three-dimensional microstructure, fiber-reinforced scaffolds have the advantage to mimic the structure, mechanical and biological environment of natural soft tissues, which benefits for their regeneration and remodeling. This article reviews and discusses the latest research advances on design and manufacture of novel fiber-reinforced scaffolds for soft tissue repair and how fiber addition affects their structural characteristics, mechanical strength and biological activities in vitro and in vivo. In general, the concept of fiber-reinforced scaffolds with adjustable microstructures, mechanical properties and degradation rates can provide an effective platform and promising method for developing satisfactory biomechanically functional implantations for soft tissue engineering or regenerative medicine.

It is generally recognized that nanoparticles possess unique physicochemical properties that are largely different from those of conventional materials, specifically the electromagnetic properties of magnetic nanoparticles (MNPs). These properties have attracted many researchers to launch investigations into their potential biomedical applications, which have been reviewed in this article. First, common types of MNPs were briefly introduced. Then, the biomedical applications of MNPs were reviewed in seven parts: magnetic resonance imaging (MRI), cancer therapy, the delivery of drugs and genes, bone and dental repair, tissue engineering, biosensors, and in other aspects, which indicated that MNPs possess great potentials for many kinds of biomedical applications due to their unique properties. Although lots of achievements have been obtained, there is still a lot of work to do. New synthesis techniques and methods are still needed to develop the MNPs with satisfactory biocompatibility. More effective methods need to be exploited to prepare MNPs-based composites with fine microstructures and high biomedical performances. Other promising research points include the development of more appropriate techniques of experiments both in vitro and in vivo to detect and analyze the biocompatibility and cytotoxicity of MNPs and understand the possible influencing mechanism of the two properties. More comprehensive investigations into the diagnostic and therapeutic applications of composites containing MNPs with "core-shell" structure and deeper understanding and further study into the properties of MNPs to reveal their new biomedical applications, are also described in the conclusion and perspectives part.

This study provided a new method to in vitro evaluate the biocompatibility of nanoscaled scaffolds for tissue engineering with neutrophils other than ordinary cell culture. The neutrophils were separated from human peripheral blood of healthy subjects. In vitro degradation product of nanohydroxyapatite/collagen (nHAC), nanohydroxyapatite/collagen/poly (L-lactic acid) (nHACP), and nHACP reinforced by chitin fibers (nHACP/CF) in the D-Hank's Balanced Salt Solution (D-HBSS) was used as the testing solution, which was thereafter mixed with the neutrophils. It was shown that the cell survival rate in the testing solutions had no significant difference from that in the D-HBSS (control). However, from both gene and protein expression levels, the lactate dehydrogenase and tumor necrosis factor-alpha of the neutrophils in the nHACP/CF testing solution were found lowest during the whole testing period; the main reasons of which might be that the calcium release rate of the scaffold was slowest and that the pH value of its degradation solution was nearest to that of human body. Moreover, in vivo experiments showed that most inflammation reactions happened for nHAC and poly (L-lactic acid) groups, while the least inflammation reactions happened for nHACP/CF group in the subcutaneous dorsum of mice at 2 weeks after the surgery, which confirmed the in vitro findings. These results indicated that the pH value and the certain metal iron concentration of the nanoscaled scaffold degradation solution should be two important factors that significantly affect its biocompatibility. This study provides a simple and effective biocompatibility test method for biodegradable nanoscaled tissue engineering scaffolds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2117-2125, 2016.

As their name suggests, conductive nanomaterials (CNMs) are a type of functional materials, which not only have a high surface area to volume ratio, but also possess excellent conductivity. Thus far, CNMs have been widely used in biomedical applications, such as effectively transferring electrical signals, and providing a large surface area to adsorb proteins and induce cellular functions. Recent works propose further applications of CNMs in biosensors, tissue engineering, neural probes, and drug delivery. This review focuses on common types of CNMs and elaborates on their unique properties, which indicate that such CNMs have a potential to develop into a class of indispensable biomaterials for the diagnosis and therapy of human diseases. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 322–339, 2016.

Over-expression of ATP-binding cassette (ABC) transporters, a large family of integral membrane proteins that decrease cellular drug uptake and accumulation by active extrusion, is one of the major causes of cancer multi-drug resistance (MDR) that frequently leads to failure of chemotherapy. Carbon nanotubes (CNTs)-based drug delivery devices hold great promise in enhancing the efficacy of cancer chemotherapy. However, CNTs' effects on the ABC transporters remain under-investigated. In this study, we found that multiwalled carbon nanotubes (MWCNTs) reduced transport activity and expression of ABC transporters including ABCB1/Pgp and ABCC4/MRP4 in human colon adenocarcinoma Caco-2 cells. Proto-oncogene c-Myc, which directly regulates ABC gene expression, was concurrently decreased in MWCNT-treated cells and forced over-expression of c-Myc reversed MWCNTs' inhibitory effects on ABCB1 and ABCC4 expression. MWCNT-cell membrane interaction and cell membrane oxidative damage were observed. However, antioxidants such as vitamin C, β-mecaptoethanol and dimethylthiourea failed to antagonize MWCNTs' down-regulation of ABC transporters. These data suggest that MWCNTs may act on c-Myc, but not through oxidative stress, to down-regulate ABC transporter expression. Our findings thus shed light on CNTs' novel cellular effects that may be utilized to develop CNTs-based drug delivery devices to overcome ABC transporter-mediated cancer chemoresistance.

The biomaterials science has advanced in a high speed with global science and technology development during the recent decades, which experts predict to be more obvious in the near future with a more significant position for medicine and health care. Although the three traditional subjects, such as medical science, materials science and biology that act as a scaffold to support the structure of biomaterials science, are still essential for the research and education of biomaterials, other subjects, such as mechanical engineering, mechanics, computer science, automatic science, nanotechnology, and Bio-MEMS, are playing more and more important roles in the modern biomaterials science development. Thus, the research and education of modern biomaterials science should require a logical integration of the interdisciplinary science and technology, which not only concerns medical science, materials science and biology, but also includes other subjects that have been stated above. This article focuses on multidisciplinary nature of biomaterials, the awareness of which is currently lacking in the education at undergraduate stage. In order to meet this educational challenge, we presented a multidisciplinary course that referred to not only traditional sciences, but also frontier sciences and lasted for a whole academic year for senior biomaterials undergraduate students with principles of a better understanding of the modern biomaterials science and meeting the requirements of the future development in this area. The course has been shown to gain the recognition of the participants by questionaries and specific “before and after” comments and has also gained high recognition and persistent supports from our university. The idea of this course might be also fit for the education and construction of some other disciplines.

Silver (Ag) nanoparticles were produced using DNA extracted from salmon milt as templates. Particles spherical in shape with an average diameter smaller than 10 nm were obtained. The nanoparticles consisted of Ag as the core with an outermost thin layer of DNA. The DNA/Ag hybrid nanoparticles were immobilized over the surface of cotton based fabrics and their antibacterial efficiency was evaluated using E. coli as the typical Gram-negative bacteria. The antibacterial experiments were performed according to the Antibacterial Standard of Japanese Association for the Functional Evaluation of Textiles. The fabrics modified with DNA/Ag nanoparticles showed a high enough inhibitory and killing efficiency against E. coli at a concentration of Ag ≥ 10 ppm.

Based on our previous finding that a chromatography with titanium beads selectively binds phosphoproteins, including caseins, phosvitin and dentin phosphoproteins, we investigated whether bone phosphoproteins also bind to titanium.Bovine bone matrix proteins were extracted with 2 M urea/PBS after demineralization.The 2 M urea extract was directly applied to the titanium chromatography column as reported.The chromatogram showed an initial large peak at breakthrough position (non-binding fraction) and a smaller second peak eluted later (titanium-binding fraction).Both peaks were analyzed by SDS polyacrylamide gel electrophoresis.Stains-all staining which preferentially identifies phospho-proteins revealed that the first peak contained no positively stained band, while the second peak showed 4 or 5 distinctive bands indicative of bone phosphoproteins.To investigate the biological functions of the titanium-binding bone proteins (TiBP), we implanted them into calvaria of rats, combined with titanium web (TW), a highly porous titanium scaffold of thin titanium-fibers.Bone TiBP induced significantly enhanced bone formation, and new bone appeared connected directly to titanium fibers, accompanied by active blood vessel formations.Control TW alone did not induce bone formation within the titanium framework.These results demonstrate that the bone titanium-binding proteins include phosphoproteins which enhance bone formation when implanted into bone with titanium.

27 Introduction Among biomaterials, nanomaterials require a special protocol to examine their biological safety. However, no satisfactory protocol has been established for safety evaluation. The embryonic stem cell test (EST) is already known as an in vitro developmental toxicity test method [1-3]. We have examined the developmental toxicities of various nanomaterials using this EST protocol [4-9]. We previously reported the application of the EST protocol to examine MWCNTs and SWCNTs in two-dimensional culture and MWCNTs in the three-dimensional culture of ES cells [4, 7, 8]. Influence of MWCNTs to Myocardial Contraction Rhythms on Differentiation of ES-D3 Cells in Three-dimensional Culture

In the field of nanomedicine, nanoparticles with various functions are required for in vivo applications such as biomedical imaging and drug delivery. Therefore, chemical functionalization of nanoparticles has been extensively investigated. Herein, nanodiamond (ND) coated with polyglycerol (PG) and its derivatives is reported to impart good solubility in a physiological environment, a stealth nature to avoid nonspecific uptake, a targeting property to be taken up by a specific cell, and an acid‐responsive drug release property to kill cancer cells. ND is first grafted with PG and the resulting ND‐PG has a high solubility in physiological media. Since a large number of hydroxyl groups in PG provide scaffolds for further surface functionalization, the targeting RGD peptide and Pt‐based drug are immobilized to give ND‐PG‐RGD, ND‐PG‐Pt and ND‐PG‐RGD‐Pt. The ND with intrinsic fluorescence is also functionalized by PG and RGD to confirm cellular uptake and intracellular localization fluorescently. The results of the cell experiments indicate that PG coating shielded fND from the uptake by HeLa and U87MG cells. In contrast, fND‐PG‐RGD is taken up by U87MG, not HeLa cells, exhibiting high targeting efficacy. When ND‐PG‐RGD‐Pt is applied, U87MG is selectively killed against HeLa. The multi‐functional ND is a promising prodrug in targeting chemotherapy.

In this study, we prepared two types of europium (Eu)-doped nanoparticle, yttoria and titania and investigated their photo-physical properties and biocompatibilities. These particles do not inhibit cell culture, even at higher concentrations. The obtained nanoparticles had a strong and narrow red photo-luminescent peak. The narrow emission was observed even when the particles were uniformly doped into a polymer film. These results suggest that they can be used for applications not only in optoelectronic devices but also in biomedical devices for bioimaging and luminescent biomedical materials. (C)2014 The Ceramic Society of Japan. All rights reserved.

In this study, we produced europium-doped yttoria (Y2O3:Eu) nanoparticles and investigated their photoluminescent properties and biocompatibility. The Y2O3:Eu nanoparticles showed excellent photoluminescent properties and cytocompatibility. We also analyzed the photophysical properties of the nanoparticles in PMMA films. When the Y2O3:Eu nanoparticles were incorporated in the polymer film, they showed a strong red emission spectrum, similar to that seen with the particles alone. Energy dispersive X-ray spectroscopy (EDS) measurements indicated that the particles were distributed homogeneously in the PMMA film. Such materials could be applied not only to optoelectronic devices but also to biomedical applications such as bioimaging tools or luminescent medical/dental adhesive materials.

It has been stated clearly that nanofillers could make an enhancement on the mechanical performances of dental composites. In order to address current shortage of traditional dental composites, fillers in forms of nanofibers or nanotubes are broadly regarded as ideal candidates to greatly increase mechanical performances of dental composites with low content of fillers. In this review, the efforts using nanofibers and nanotubes to reinforce mechanical performances of dental composites, including polymeric nanofibers, metallic nanofibers or nanotubes, and inorganic nanofibers or nanotubes, as well as their researches related, are demonstrated in sequence. The first purpose of current paper was to confirm the enhancement of nanofibers or nanotubes’ reinforcement on the mechanical performances of dental restorative composite. The second purpose was to make a general description about the reinforcement mechanism of nanofibers and nanotubes, especially, the impact of formation of interphase boundary interaction and nanofibers themselves on the advanced mechanical behaviors of the dental composites. By means of the formation of interface interaction and poststretching nanofibers, reinforced effect of dental composites by sorts of nanofibers/nanotubes has been successfully obtained.

78 Introduction Long-term exposure to nanomaterials causes the marked health-related anxiety of society, as observed for asbestos [1-4]. In addition, the effects of these nanomaterials on the next generation remain unknown. The embryotoxicity of nanomaterials in human organs is being investigated using the Embryo Stem Test (EST). However, few embryotoxicity studies have been conducted using cell lines other than ES-D3 cells used for the EST method [5-15]. ES-D3 cells are special ES cells that do not require feeder cells. In the present study, we considered that the results obtained with other ES cell lines were useful for ensuring data reliability. [9] Thus, the effects of C60 fullerene, mechanically dispersed Effects of C60 Fullerene on Cell Differentiation with EL-M3 and ES-R1-EGFP B2/EGFP Cell Lines

A successful targeted drug delivery device for cancer chemotherapy should ideally be able to avoid non-specific uptake by nonmalignant cells, particularly the scavenging monocyte-macrophage system as well as targeting efficacy to bring the drug preferentially into tumor cells. To this purpose, we developed a platform based on detonation nanodiamond (dND) with hyperbranched polyglycerol (PG) coating (dND-PG). dND-PG was first demonstrated to evade non-specific cell uptake, particularly by macrophages (U937). RGD targeting peptide was then conjugated to dND-PG through multistep organic transformations to yield dND-PG-RGD that still evaded macrophage uptake but was preferentially taken up by targeted A549 cancer cells (expressing RGD peptide receptors). dND-PG and dND-PG-RGD showed good aqueous solubility and cytocompatibitlity. Subsequently, the anticancer agent doxorubicin (DOX) was loaded through acid-labile hydrazone linkage to yield dND-PG-DOX and dND-PG-RGD-DOX. Their cellular uptake and cytotoxicity were compared against DOX in A549 cells and U937 macrophages. It was found that dND-PG-DOX uptake was substantially reduced, displaying little toxicity in either type of cells by virtue of PG coating, whereas dND-PG-RGD-DOX exerted selective toxicity to A549 cells over U937 macrophages that are otherwise highly sensitive to DOX. Finally, dND-PG was demonstrated to have little influence on U937 macrophage cell functions, except for a slight increase of TNF-α production in resting U937 macrophages. dND-PG is a promising drug carrier for realization of highly selective drug delivery in tumor cells through specific uptake mechanisms, with minimum uptake in and influence on macrophages.