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Epimedii Folium (Yinyanghuo in Chinese) is one of the most commonly used traditional Chinese medicines. Its main active components are flavonoids, which exhibit multiple biological activities, such as promotion of bone formation and sexual function, protection of the nervous system, and prevention of cardiovascular diseases. Flavonoids also show anti-inflammatory and anticancer effects. Various effective methods, including genetic and chemical approaches, have been developed for the quality control of Yinyanghuo. In this review, the studies conducted in the last decade about the chemical constituents, quality control, and bioactivity of Yinyanghuo are summarized and discussed.

In this paper, low temperature, economical sol–gel combustion method was adopted to synthesize wollastonite ceramic. Calcium nitrate tetrahydrate and tetraethyl orthosilicate were taken as source for Ca and Si, while citric acid and nitric acid were used as chelating/combustion agents. The yielded powder calcined at 600${}^{\circ }$C for 4 h was characterized by FTIR, XRD and SEM techniques. Results showed that the citrate combustion method was the most efficient method to prepare wollastonite at low temperature. Moreover, in vitro bioactivity test performed in simulated body fluid (SBF) showed good bioactivity of synthesized wollastonite ceramics.

Bioglasses are promising alternatives as biomedical materials to repair or replace damaged parts of bones because of its good bioactivity and biocompatibility. It is possible to combine the bone-bonding ability of the bioglass surface with the high mechanical properties of the metallic substrate though the coating of metallic implants with bioglass. The principles and characteristics of some coating techniques, including sintering, plasma spray, sol-gel, electrophoresis deposition, ion beam assisted deposition and pulsed laser deposition, are introduced. Their current applications in preparing bioglass coatings are reviewed in detail. The future application trends are also reviewed.

Porous NiTi shape memory alloy (SMA) with 48% porosity and an average pore size of 50–800 μm was synthesized by capsule-free hot isostatic pressing (CF-HIP). To enhance the surface bioactivity, the porous NiTi SMA was subjected to H₂O₂ and subsequent NaOH treatment. Scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy analyses revealed that a porous sodium titanate (Na₂TiO₃) film had formed on the surface of the porous NiTi SMA. An apatite layer was deposited on this film after immersion in simulated body fluid at 37°C, while no apatite could be found on the surface of the untreated porous NiTi SMA. The formation of the apatite layer infers that the bioactivity of the porous NiTi SMA may be enhanced by surface chemical treatment, which is favorable for its application as bone implants.

Titanium alloys are superior of biocompatibility, mechanical properties and chemical stability. The biocompatibility of Ti alloy is related to the surface effect between human tissue and implant. Therefore, the purpose of this study is to investigate the bioactivity of Ti alloy by alkali and acid chemical surface treatment; and the biocompatibility of Ti alloy was evaluated by in vitro test. Higher bone-bonding ability and bioactivity of the substrate were obtained by the formation of apatite layers on the Ti alloy in simulated body fluid. The microstructures of apatite layer were investigated by scanning electron microscope (SEM) and the formed phases were analyzed with X-ray diffraction (XRD).

Glass-ceramics containing only apatite and wollastonite crystals were produced in the system MgO-CaO-SiO₂-P₂O₅-F by the melt casting process. The bioactivity of the glass-ceramics was determined by immersing the glass-ceramics in a simulated body fluid (SBF) and by assessing the resulting apatite formation on the free surface after various immersion durations. A 12-μm-thick apatite layer formed on the surface of the glass-ceramic containing only apatite crystals after 20 days immersion in SBF. However, the thickness of the apatite layer formed on the surface of the glass-ceramic containing apatite and wollastonite crystals was 1 μm. Results have shown that the bioactivity of glass-ceramic depends strongly on the type of crystal(s) developed during the glass-ceramic process and their proportion in the glassy matrix.

In the present work, the effect of K₂O/Na₂O substitution on the bioactivity of Na₂O-CaO-P₂O₅-SiO₂ ceramics prepared by solid-state method was studied. Ceramics-based bioactive implants are economical; they require low processing temperature and are more bioactive when compared with glasses, glass ceramics and composites. K₂O is known to control proper function of cells and stimulate bone formation process. The hydroxyapatite layer developed on the surface of samples after soaking in stimulated body fluid solution was studied by X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy and atomic absorption spectroscopy. The results showed an increase in the bioactivity of the samples as Na₂O was partially replaced with K₂O. The addition of K₂O enhanced the apatite-forming ability of the ceramic samples and makes it suitable for filling defects and fracture in bones.

The present work deals with the fabrication of forsterite–hydroxyapatite (FS–HA) hybrid coatings on stainless-steel 316L using the pulsed laser deposition (PLD) technique. The stainless steel (SS 316L) as a metallic implant is widely used in hard tissue applications. The XRD studies have confirmed the crystalline behavior of synthesized FS powder with an average crystallite size of 54nm. The synthesized FS powder was mixed in different compositions (10, 20, 30wt.%) into HA for preparing PLD targets (pellets). The XRD of the prepared pellets by UTM has confirmed both phases of FS and HA. The Scanning Electron Microscopy (SEM) of the coated samples depicted the successful deposition of composite powders on the substrates (SS 316L). The Ellipsometer was used to investigate the thickness of different substrates and it was found as 243, 251, 255, and 257nm for CP1, CP2, CP3, and CP4, respectively. The bioactivity of the coated substrates with different compositions (pure HA, 10%, 20%, 30%, and pure FS) was investigated by immersing the samples in simulated body fluid (SBF) for 14days. The same samples were then characterized by SEM which confirms the apatite layer formation that reflects the bioactivity. The addition of FS powder into HA will stimulate the apatite formation which enhances the bioactivity. The Raman Spectroscopy of coated samples reveals the successful deposition of different compositions of FS–HA nanocomposite. The peaks of Raman spectroscopy were corresponding to the XRD results of the pellets (different compositions of FS–HA). The antimicrobial activity of different compositions of FS–HA against Escherichia coli (E. coli) bacteria also showed a significant zone of inhibition. The bioactivity and antimicrobial behavior of FS–HA along with successful deposition by PLD have shown better potential applications for biomedical implant coating.

The modern process of discovering candidate molecules in early drug discovery phase includes a wide range of approaches to extract vital information from the intersection of biology and chemistry. A typical strategy in compound selection involves compound clustering based on chemical similarity to obtain representative chemically diverse compounds (not incorporating potency information). In this paper, we propose an integrative clustering approach that makes use of both biological (compound efficacy) and chemical (structural features) data sources for the purpose of discovering a subset of compounds with aligned structural and biological properties. The datasets are integrated at the similarity level by assigning complementary weights to produce a weighted similarity matrix, serving as a generic input in any clustering algorithm. This new analysis work flow is semi-supervised method since, after the determination of clusters, a secondary analysis is performed wherein it finds differentially expressed genes associated to the derived integrated cluster(s) to further explain the compound-induced biological effects inside the cell. In this paper, datasets from two drug development oncology projects are used to illustrate the usefulness of the weighted similarity-based clustering approach to integrate multi-source high-dimensional information to aid drug discovery. Compounds that are structurally and biologically similar to the reference compounds are discovered using this proposed integrative approach.

Bioactive SiO₂-CAO-P₂O₅ gel (BAG) nanoparticles with 40 nm in diameter were synthesized by the sol-gel route and further modified via the ring-opening polymerization of lactide on the surface of particles. Surface modified BAG (mBAG) was introduced in poly(L-lactide) (PLLA) matrix as bioactive filler. The dispersibility of mBAG in PLLA matrix was much higher than that of rough BAG particles. Tensile strength of the mBAG/PLLA composite could be increased to 61.2 MPa at 2 wt% filler content from 53.4 MPa for pure PLLA. The variation of moduli of the BAG/PLLA and mBAG/PLLA composites always showed an enhancement tendency with the increasing content of filler loading. The SEM photographs of the fracture surfaces showed that mBAG could be homogeneously dispersed in the PLLA matrix, and the corrugated deformation could absorb the rupture energy effectively during the breaking of materials. In vitro bioactivity tests showed that both BAG and mBAG particles could endow the composites with ability of the calcium sediment in SBF, but the surface modification of BAG particles could weaken this capability to some extent. Biocompatibility tests showed that both BAG and mBAG particles could facilitate the attachment and proliferation of the marrow cells on the surface of the composite. All these results showed that the mBAG/PLLA composite would be a promising material for bone tissues regeneration.

A facile and cost-effective sol–gel technique has been used to synthesize nickel chromite (NiCr₂O₄) nanoparticles (NCNPs) at $700^{\circ }$C to investigate their photocatalytic together with antibacterial and anticancer activities. The synthesized nanopowder was characterized by Thermogravimetric thermal analysis (TG-DTA), X-ray Diffraction Spectroscopy (XRD), Field Emission Scanning Electron Microscopy (FE-SEM), High-Resolution Transmission Electron Microscopy (HR-TEM), Fourier Transform-Infrared Spectroscopy (FT-IR), X-ray Photon Electroscopy (XPS) and UV–Visible Diffuse Reflectance Spectroscopy (UV-DRS) and Photoluminescence (PL). Beyond $700^{\circ }$C, the thermal durability of NCNPs was confirmed by TG-DTA analysis. The synthesized NPs were cubic structured corresponding to their spinel structure, a crystallite size of 38nm and an optical bandgap of 2.7 eV. The PL spectra revealed emission bands in the visible and UV regions. The surface-phase-pure elemental and electronic arrangement of the NCNPs were verified by X-ray photon spectroscopy. Photocatalytic activity of NCNPs against Methylene Blue dye revealed 89% degradation in 1 h. The in vitro antibacterial and anticancer activities of NCNPs were also examined. Among the tested microbes, Staphylococcus aureus exhibited the highest level of sensitivity (9 mm), while Escherichia coli had the lowest (5 mm) against NCNPs. The MTT test revealed the significant cytotoxicity of NCNPs against carcinogenic HeLa and MCF-7 cells. Thus, the synthesized NCNPs could be rated as potential photocatalytic, bactericidal and anticarcinogenic agents.

We developed surface modification technologies for dental implants in this study. The study contributes to shortening the time required for adhesion between alveolar bone and fixtures which consist of dental implants. A Nd:YVO₄ nanosecond laser was used to modify the surfaces of commercially pure titanium (CP Ti) disks, and their biocompatibility was evaluated cytocompatibility and bioactivity. First, rows of 200 µm spaced rectilinear laser treatments were performed on surfaces of CP Ti disks. Osteoblasts derived from rat mesenchymal stem cells were then cultured on the treated surfaces. Cytocompatibility on the laser treated area was evaluated by observing adhesion behavior of cells on these surfaces. The results indicated that the micro-order structure formed by the laser treatment promoted adhesion of osteoblasts and that traces of laser treatment without microstucture didn't affect the adhesion. Second, surfaces of CP Ti disks were completely covered by traces of laser treatment, which created complex microstructures of titania whose crystal structure is rutile and anatase. This phenomenon allowed the creation of hydroxyapatite on the surface of the disks in 1.5-times simulated body fluid (1.5SBF) while no hydroxyapatite was observed on conventional polished surfaces in the same conditions. This result indicates that bioactivity was enabled on CP Ti by the laser treatment. From these two results, laser treatment for CP Ti surfaces is an effective method for enhancing adhesion of osteoblasts and promoting bioactivity, which are highly appreciated properties for dental implants.

Exposure to ultra-violet (UV)-C radiation is a frequently used method to prevent bacteria from invasion of blood-contact biomedical products. Potential damage induced by UV radiation to collagen is of concern due to the decay of bioactivity, considerably correlated with structural alterations. Current investigation indicates to the collagen-immobilized non-woven polypropylene (PP) fabrics with sample temperature ca. 4 °C; the samples are then exposed to UV-254 nm radiation for different time intervals. Using Fourier-Transformed Infrared with Attenuated Total Reflection (FTIR-ATR) and XPS (X-ray Photoelectron Spectroscopy), we examine the chemical structures of samples with different treatments. Blood-clotting effects on the modified samples are assessed by activated partial thromboplastin time, thrombin time, and fibrinogen concentration tests. By means of cell counter and Scanning Electron Microscopy we count red blood cells and platelets adhesion in the modified porous matrix. Applying standard plate count for bacteria tests, E. coli, Bacillus stearothermophilus, Staph. aureus, P. aeruginosa, and Candida albieans are applied. For human plasma incubated samples of various intervals of UV-254 nm radiation, fibrinogen concentration decreases in human plasma, while platelets and red blood cells adhesions increase before UV radiation. The required time for thrombination shows significant change for UV exposure of less than 20 hrs (α = 0.05). Surface analyses indicate that the decrease of R-COOH (derivated from grafted-pAAc or decarboxylation of collagen), amides degradation (broken–NH), and phenylalanine scission (terminated by −OH, tyrosine formation) may gradually damage collagen by increasing the intervals of UV radiation. The XPS measurements of C 1s core levels at 288.1 eV (O=C-NH) and at 289.3 eV (O=C-O) illustrate significant decreases of intensity after radiation time ca. 44 hrs. It is clear that UV-254 nm radiation exposure for ca. 20 hrs has the potential impact to moderate the bioactivities of collagen and therefore act as a vital factor to accelerate bio-degradation. Bacteria test also supports that around 20 hrs of UV radiation, no bacteria clone formation is found on the immobilized collagen. However, the relation between eventual bioactivity of immobilized collagen after UV radiation and the capability of bacteria proliferation should be measured.

Commercially pure titanium was treated with an H₂O₂/TaC1₅ solution. Thus formed titania gel layer remained amorphous when heated below 200°C and transformed to anatase after heated between 300-600°C. The anatase layers were substantially bioactive to deposit carbonate ion-incorporated apatite after soaked for 1 d in a simulated body fluid (Kokubo’s recipe), while the amorphous layers did not deposit up to 7 d. The apatite particles were preferably nucleated inside the cracks which prevailed in the titania gel layers. After soaking only for 2 d, the specimens were almost completely covered by the apatite. The H₂O₂-treated Ti specimens deposited apatite on both the contact and open surfaces, whereas the NaOH treated Ti specimens only deposited on the contact surfaces. The elimination of peroxide radicals out of titania gel and formation of anatase during heating are considered to be responsible for the improvement of apatite deposition ability.

It was already revealed that a sol-gel-derived titania forms an apatite on its surface in a simulated body fluid (SBF). It is, however, not clear what structure of titania gel is effective for inducing apatite nucleation on its surface. In the present study, apatite-forming ability of titania gels with different structures, which were formed in different media and heat-treated at different temperatures, were investigated in SBF. The titania gels heat-treated at 300°C took amorphous phases and did not form the apatite on their surfaces even after 14 days irrespective of the media. The titania gels, which were prepared in media containing no additive or acetylacetone and heat-treated at 500 to 800°C to precipitate anatase, formed the apatite on their surfaces within 7 days in SBF. The titania gels, which were prepared in a medium containing diethanolamine and heat-treated at 700 to 800°C to precipitate rutile, formed the apatite within 14 days in SBF. This indicates that a specific structure of titania such as anatase structure is effective for inducing apatite nucleation.

The bioactivity of electrolytically coated hydroxyapatite (HA) on titanium substrates was investigated and compared with titanium sheets with three different surface treatments: machined, blasted with Al₂O₃ and plasma-sprayed with titanium. This paper reports the results of an in vitro study using simulated body fluid (SBF). The specimens were examined by scanning electron microscopy (SEM), and X-rays diffraction spectroscopy (XRD). The SBF solutions of each specimen were analysed by ICPMS. SEM analysis after 7 days of incubation showed hydroxyapatite precipitation in the HA coated specimens, and this was confirmed by the XRD and ICPMS analysis. The SEM and XRD analysis indicated the absence of HA precipitation in the non-coated specimens, even after 35 days.

The effect of low levels of silicon-substitution on the biocompatability, bioactivity and the surface apatite layer forming ability of hydroxyapatite was demonstrated by studying three different compositions: stoichiometric HA and 0.8 and 1.6wt% silicon substituted hydroxyapatite (Si-HA). The apatite-forming ability of the three compositions was determined by immersing the samples in Simulated Body Fluid (SBF K-9). Thin Film X-ray Diffraction (TF-XRD) and Scanning Electron Microscopy (SEM) showed that the time required to form a surface apatite layer (SAL) decreased with increasing silicon substitution. A human osteosarcoma (HOS TE 85) cell line was used to evaluate the effect of incorporating silicon into the lattice of HA on its in vitro biocompatability. A MTT assay indicated that all samples were non-cytotoxic and the mitochondrial activity of the cells cultured in eluates obtained from the 0.8wt% Si-HA showed a statistically significant increase compared to the negative control (Thermanox^TM) and stoichiometric HA. From the results of the alamarBlue^TM assay, the metabolic activity of HOS cells on 0.8 and 1.6wt% Si-HA compositions was increased for all time points, compared to stoichiometric hydroxyapatite. This study has shown that silicon-substituted hydroxyapatite bioceramics enhance the formation of a surface apatite layer in an artificial physiological solution and stimulate osteoblast-like cell activity in vitro, compared to stoichiometric HA.

We recently showed that pure titanium metal chemically treated with hydrogen peroxide solution containing tantalum chloride has the ability to bond to bone directly. The purpose of this study is to examine effectiveness of the treatment on titanium alloy. The treatment was applied to a Ti-6A1-4V cylinder (4.0 mm in diameter, 20.0 mm in length). The specimen was implanted into a whole (4.0 mm in diameter) in a rabbit’s tibia. After implantation for predetermined periods up to 8 weeks, the specimens were extracted with bone tissue, and were examined by push-out test to evaluate the shearing force between the implant and bone tissue. The results were compared with those of non-treated titanium alloy as well as of pure titanium metal. Four weeks after surgery, the shearing force of the treated titanium implanted was higher than that of the non-treated titanium. Comparing titanium alloy with pure titanium, no significant difference was found at 4 and 8 weeks after surgery. Thus, it is confinned that the treatment with hydrogen peroxide solution containing tantalum chloride can provide Ti-6A1-4V alloy with bone-bonding ability, based on a similar mechanism on pure titanium metal.

This study was carried out to investigate the effects of alkali and heat treatments on the bone-bonding behavior of porous titanium implants. A porous titanium rod, 6 mm in diameter, was manufactured. This rod had 4.6 mm solid core and 0.7 mm-thick porous outer layer using pure titanium plasma-splay technique. This rod was cut transversely into pieces of 13 mm long. Three kinds of porous implants were prepared from these pieces: 1) control ; as manufactured (CL), 2) AW- glass ceramic bottom coated (AW), 3) Alkali- and heat-treated (AH) (5 mol/LNaOH 60°C for 24 h and 600°C 1 h). The implants were inserted into canine femora hemi-transcortically. At 4 and 12 weeks after implantation the bone-bonding shear strengths of the implants were analyzed with push out test and histological and histomorphometncal analysis were also performed At 4 weeks the AH implants showed significantly higher shear strength than the CL implants. At 12 weeks there was no significant difference among the bonding strengths of the three types of the porous implants. There was no difference in bone ingrowth into porous portion of the three types of the implants at both 4 and 12 weeks, while direct bone contact with implant surface was significantly higher in the AH implants than the CL and AW implants both at 4 and 12 weeks. In conclusion, alkali and heat treatments can provide the porous titanium implants with earlier stable fixation.

This study evaluated the possibility of obtaining bioactive coatings on polyethylene/bioactive glass composites exhibiting a very good mechanical performance. High molecular weight polyethylene (HMWPE) was reinforced with 10 to 40% (wt.) of a bioactive glass (BGE1) and a glass-ceramic (BGE1C), in the SiO₂-3CaOP₂O₅-MgO system. The composites were compounded by twin-screw extrusion (TSE) and then injection moulded into dumb-bell tensile samples. The composites presenting adequate mechanical properties were then coated with a bioactive layer by two methodologies: (i) an adapted biomimetic route using a similar glass as a precursor of calcium-phosphate (Ca-P) film deposition, and (ii) the production of a ‘sandwich’ with bioactive glass particles, previously mixed with UHMWPE powders, made to adhere to both faces of tensile samples by compression moulding. The obtained results indicated that it is possible to produce composites presenting a modulus of 11.2 GPa coupled with a tensile strength of around 117 MPa. The developed composites could be coated with a Ca-P layer by an adapted biomimetic route. Furthemore, the ‘sandwich’ route allowed for the production of load-bearing composites, presenting a highly bioactive surface, which strongly adheres to the HMWPE matrix composites.