One-Pot Synthesis of Bi2 S3 /TiO2 /rGO Heterostructure with Red Light-Driven Photovoltaic Effect for Remote Electrotherapy-Assisted Wound Repair.

The past decades have witnessed the rational design of novel functional nanomaterials and the potential to revolutionize many applications. With the increasing focus on electronic biological processes, novel photovoltaic nanomaterials are highly expectable for empowering new therapeutic strategies such as establishing a link between endogenous electric field (EEF) and electrotherapy. Compared to traditional invasive stimulation, the light-initiating strategy has the advantages of non-invasion, non-power supply, and precise controllability. Whereas, common photoactivated materials require short-wavelength light excitation accompanied by poor tissue penetration and biohazard. Herein, by the construction of p-n heterostructured Bi2 S3 /TiO2 /rGO (BTG) nanoparticles, broadener light absorption and higher light conversion than regular UV excitation are realized. Simultaneously, the photoelectric performance of BTG heterostructure, as well as the synergistic effect of Bi2 S3 morphology, are revealed. Besides, the rationally designed biomimetic hydrogel matrix consisting of collagen and hyaluronic acid provides appropriate bioactivity, interface adhesion, mechanical matching, and electron transfer. Therefore, the photovoltaic BTG-loaded matrix provides a platform of light-driven electrical stimulation, coupling the EEF to modulate the electrophysiological and regeneration microenvironment. The implementation of photoelectric stimulation holds broad prospects for non-drug therapy and electrical-related biological process modulation including osseointegration, nerve regeneration, electronic skin, and wound healing.

Flexible silk-fibroin-based microelectrode arrays for high-resolution neural recording.

High-precision neural recording plays a pivotal role in unraveling the intricate mechanisms that underlie information transmission of the nervous system, raising increasing interest in the development of implantable microelectrode arrays (MEAs). The challenge lies in providing a truly soft, highly conductive and low-impedance neural interface for precise recording of the electrophysiological signals of individual neurons or neural networks. Herein, by implementing a novel topological regulation strategy of silk fibroin (SF) crosslinking, we prepared a flexible, hydrophilic, and biocompatible MEA substrate, facilitating a biocompatible neural interface that minimizes mechanical mismatch with biological tissues. Additionally, we established a strategy involving screen-printing combined with post-coating to prepare MEAs with high conductivity, low impedance and high capacitance, by coating PEDOT:PSS on titanium carbide (Ti3C2) microarrays. The Ti3C2 nanosheets, as the conductive track of the MEAs, avoided the charge drifting associated with metals and facilitated the processing of the MEAs. Further coating PEDOT:PSS on the electrode points reduced the impedance 100-fold, from 105 to 103 Ω. Experimental validation confirmed the superior electrophysiological signal recording capabilities of the SF-based MEA (SMEA) in peripheral and cerebral nerves with a much higher signal-to-noise ratio (SNR) of 20. In particular, we achieved high-precision recording of the action potential (AP) induced by flash visual stimulation, demonstrating high performance in weak signal recording. In summary, the development of SMEA provides a robust foundation for future investigations into the mechanisms and principles of neural circuit information transmission in complex nervous systems.

Wireless-Powering Deep Brain Stimulation Platform Based on 1D-Structured Magnetoelectric Nanochains Applied in Antiepilepsy Treatment.

Electrical deep brain stimulation (DBS) is a top priority for pharmacoresistant epilepsy treatment, while less-invasive wireless DBS is an urgent priority but challenging. Herein, we developed a conceptual wireless DBS platform to realize local electric stimulation via 1D-structured magnetoelectric Fe3O4@BaTiO3 nanochains (FBC). The FBC was facilely synthesized via magnetic-assisted interface coassembly, possessing a higher electrical output by inducing larger local strain from the anisotropic structure and strain coherence. Subsequently, wireless magnetoelectric neuromodulation in vitro was synergistically achieved by voltage-gated ion channels and to a lesser extent, the mechanosensitive ion channels. Furthermore, FBC less-invasively injected into the anterior nucleus of the thalamus (ANT) obviously inhibited acute and continuous seizures under magnetic loading, exhibiting excellent therapeutic effects in suppressing both high voltage electroencephalogram signals propagation and behavioral seizure stage and neuroprotection of the hippocampus mediated via the Papez circuit similar to conventional wired-in DBS. This work establishes an advanced antiepilepsy strategy and provides a perspective for other neurological disorder treatment.

Hydrogels of collagen/chondroitin sulfate/hyaluronan interpenetrating polymer network for cartilage tissue engineering.

The network structure of a three-dimensional hydrogel scaffold dominates its performance such as mechanical strength, mass transport capacity, degradation rate and subsequent cellular behavior. The hydrogels scaffolds with interpenetrating polymeric network (IPN) structure have an advantage over the individual component gels and could simulate partly the structure of native extracellular matrix of cartilage tissue. In this study, to develop perfect cartilage tissue engineering scaffolds, IPN hydrogels of collagen/chondroitin sulfate/hyaluronan were prepared via two simultaneous processes of collagen self-assembly and cross linking polymerization of chondroitin sulfate-methacrylate (CSMA) and hyaluronic acid-methacrylate. The degradation rate, swelling performance and compressive modulus of IPN hydrogels could be adjusted by varying the degree of methacrylation of CSMA. The results of proliferation and fluorescence staining of rabbit articular chondrocytes in vitro culture demonstrated that the IPN hydrogels possessed good cytocompatibility. Furthermore, the IPN hydrogels could upregulate cartilage-specific gene expression and promote the chondrocytes secreting glycosaminoglycan and collagen II. These results suggested that IPN hydrogels might serve as promising hydrogel scaffolds for cartilage tissue engineering.

A mechanically adaptive hydrogel neural interface based on silk fibroin for high-efficiency neural activity recording.

A flexible non-transient electrical platform that can realize bidirectional neural communication from living tissues is of great interest in neuroscience to better understand basic neuroscience and the nondrug therapy of diseases or disorders. The development of soft, biocompatible, and conductive neural interface with mechanical coupling and efficient electrical exchange is a new trend but remains a challenge. Herein, we designed a multifunctional neural electrical communication platform in the form of a mechanically compliant, electrically conductive, and biocompatible hydrogel electrode. Silk fibroin (SF) obtained from Bombyx Mori cocoons was compounded with aldehyde-hyaluronic acid (HA-CHO) with a dynamic network to delay or interrupt the ß-sheet-induced hardening of SF chains, resulting in the fabrication of a hydrogel matrix that is mechanically matched to biological tissues. Moreover, the incorporation of functionalized carbon nanotubes (CNTs) facilitated interaction and dispersion and enabled the formation of a hydrogel electrode with a high-current percolation network, thus contributing toward improving the electrical properties in terms of conductivity, impedance, and charge storage capabilities. These advances allow high-efficiency stimulation and the recording of neural signals during in vivo implantation. Overall, a wide range of animal experiments demonstrate that the platform exhibits minimal foreign body responses, thus showing it to be a promising electrophysiology interface for potential applications in neuroscience.

Construction of a magnesium hydroxide/graphene oxide/hydroxyapatite composite coating on Mg-Ca-Zn-Ag alloy to inhibit bacterial infection and promote bone regeneration.

The improved corrosion resistance, osteogenic activity, and antibacterial ability are the key factors for promoting the large-scale clinical application of magnesium (Mg)-based implants. In the present study, a novel nanocomposite coating composed of inner magnesium hydroxide, middle graphene oxide, and outer hydroxyapatite (Mg(OH)2/GO/HA) is constructed on the surface of Mg-0.8Ca-5Zn-1.5Ag by a combined strategy of hydrothermal treatment, electrophoretic deposition, and electrochemical deposition. The results of material characterization and electrochemical corrosion test showed that all the three coatings have high bonding strength, hydrophilicity and corrosion resistance. In vitro studies show that Mg(OH)2 indeed improves the antibacterial activity of the substrate. The next GO and GO/HA coating procedures both promote the osteogenic differentiation of MC3T3-E1 cells and show no harm to the antibacterial activity of Mg(OH)2 coating, but the latter exhibits the best promoting effect. In vivo studies demonstrate that the Mg alloy with the composite coating not only ameliorates osteolysis induced by bacterial invasion but also promotes bone regeneration under both normal and infected conditions. The current study provides a promising surface modification strategy for developing multifunctional Mg-based implants with good corrosion resistance, antibacterial ability and osteogenic activity to enlarge their biomedical applications.

Application of femtosecond laser microfabrication in the preparation of advanced bioactive titanium surfaces.

The surface activation of titanium plays a key role in the biological properties of titanium implants as bone repair materials. Improving the ability to induce apatite precipitation on the surface was a well-accepted titanium bioactivation route. In this study, advanced femtosecond laser microfabrication was applied to modify titanium surfaces, and the effect of femtosecond laser etching on apatite precipitation was investigated and compared with popular titanium modification methods. Meanwhile, the mechanism of apatite formation after femtosecond laser modification was interpreted from the point of materials science. The surface physical-chemical characterization results showed that femtosecond laser etching can improve the surface hydrophilicity and increase the surface energy. Compared with traditional abrasive paper and acid-alkali treatment, this method increased the contents of active sites including titanium oxide and titanium-hydroxyl on titanium surfaces. TiO2 on the surface was transformed to TiO after femtosecond laser treatment. The samples etched with 0.3 W and 0.5 W femtosecond lasers had a better ability to induce apatite deposition than those treated with traditional mechanical treatment and popular acid-alkali modification, which would lead to better bioactivity and osteointegration. Considering the technical advantages of femtosecond lasers in microfabrication, it provides a more efficient and controllable scheme for the bioactivation of titanium. This research would improve the application potential of femtosecond laser treatment, such as micropattern preparation and surface activation, in the field of biomaterials.

Variation of rhizosphere microbial community in continuous mono-maize seed production.

Soil microbe is crucial to a healthy soil, therefore its diversities and abundances under different conditions are still need fully understand.The aims of the study were to characterize the community structure and diversity of microbe in the rhizosphere soil after continuous maize seed production, and the relationship between the disease incidence of four diseases and the variation of the rhizosphere microbe. The results showed that different fungal and bacterial species were predominant in different cropping year, and long-term maize seed production had a huge impact on structure and diversity of soil microbial. Ascomycota and Mortierellomycota were the dominant fungal phyla and Mortierella and Ascomycetes represented for a large proportion of genus. A relative increase of Fusarium and Gibberella and a relative decrease of Mortierella, Chrysosporium, Podospora, and Chaetomium were observed with the increase of cropping year. Pathogenic Fusarium, Curvularia, Curvularia-lunata, Cladosporium, Gibberella-baccata, and Plectosphaerellaceae were over-presented and varied at different continuous cropping year, led to different maize disease incidence. Proteobacteria and Actinobacteria ranked in the top two of all bacterial phyla, and genus Pseudarthrobacter, Roseiflexus and RB41 dominated top 3. Haliangium and Streptomyces decreased with the continuous cropping year and mono-cropping of maize seed production increased disease incidence with the increase of cropping year, while the major disease was different. Continuous cropping of maize seed production induced the decrease of protective microbe and biocontrol genera, while pathogenic pathogen increased, and maize are in danger of pathogen invasion. Field management show great effects on soil microbial community.

Magnetoelectric Nanoparticles Incorporated Biomimetic Matrix for Wireless Electrical Stimulation and Nerve Regeneration.

Electrical stimulation is regarded pivotal to promote repair of nerve injuries, however, failed to get extensive application in vivo due to the challenges in noninvasive electrical loading accompanying with construction of biomimetic cell niche. Herein, a new concept of magneto responsive electric 3D matrix for remote and wireless electrical stimulation is demonstrated. By the preparation of magnetoelectric core/shell structured Fe3 O4 @BaTiO3 NPs-loaded hyaluronan/collagen hydrogels, which recapitulate considerable magneto-electricity and vital features of native neural extracellular matrix, the enhancement of neurogenesis both in cellular level and spinal cord injury in vivo with external pulsed magnetic field applied is proved. The findings pave the way for a novel class of remote controlling and delivering electricity through extracellular niches-mimicked hydrogel network, arising prospects not only in neurogenesis but also in human-computer interaction with higher resolution.

Biomimetic mineralized microenvironment stiffness regulated BMSCs osteogenic differentiation through cytoskeleton mediated mechanical signaling transduction.

Construction of biomimetic microenvironment is vital to understand the relationship between matrix mechanical cues and cell fate, as well as to explore potential tissue engineering scaffolds for clinical application. In this study, through the enzymatic mineralizable collagen hydrogel system, we established the biomimetic bone matrix which was capable of realizing mechanical regulation independent of mineralization by incorporation of phosphorylated molecules (vinylphosphonic acid, VAP). Then, based on the biomimetic mineralized matrix with same composition but significantly different mechanical stiffness, we further investigated the effect of matrix stiffness on osteogenic differentiation of bone marrow stromal cells (BMSCs). The results clearly demonstrated that biomimetic mineralized microenvironment with higher mechanical strength promoted osteogenic differentiation of BMSCs. Further mechanism analysis demonstrated that the mineralized hydrogel with higher stiffness promoted cytoskeletal assembly, which enhanced the expression and nuclear colocalization of YAP and RUNX2, thereby promoted the osteogenic differentiation of stem cells. This study supplies a promising material platform not only for bone tissue engineering but also for exploring the mechanism of biomimetic bone matrix mechanics on osteogenesis.

Electrochemical Deposition of Nanostructured Hydroxyapatite Coating on Titanium with Enhanced Early Stage Osteogenic Activity and Osseointegration.

PURPOSE: The aim of research is to fabricate nanostructured hydroxyapatite (HA) coatings on the titanium via electrochemical deposition (ED). Additionally, the biological properties of the ED-produced HA (EDHA) coatings with a plate-like nanostructure were evaluated in vitro and in vivo by undertaking comparisons with those prepared by acid/alkali (AA) treatment and by plasma spray-produced HA (PSHA) nanotopography-free coatings. MATERIALS AND METHODS: Nanoplate-like HA coatings were prepared through ED, and nanotopography-free PSHA coatings were fabricated. The surface morphology, phase composition, roughness, and wettability of these samples were investigated. Furthermore, the growth, proliferation, and osteogenic differentiation of MC3T3-E1 cells cultured on each sample were evaluated via in vitro experiments. Histological assessment and push-out tests for the bone-implant interface were performed to explore the effect of the EDHA coatings on the interfacial osseointegration in vivo. RESULTS: XRD analysis showed that the strongest intensity for the EDHA coatings was at the (002) plane rather than at the regular (211) plane. Relatively higher surface roughness and greater wettability were observed for the EDHA coatings. Cellular experiments revealed that the plate-like nanostructured EDHA coatings not only possessed an ability, similar to that of PSHA coatings, to promote the adhesion and proliferation of MC3T3-E1 cells but also demonstrated significantly enhanced early or intermediate markers of osteogenic differentiation. Significant osseointegration enhancement in the early stage of implantation period and great bonding strength were observed at the interface of bone and EDHA samples. In comparison, relatively weak osseointegration and bonding strength of the bone-implant interface were observed for the AA treatment. CONCLUSION: The biological performance of the plate-like nanostructured EDHA coating, which was comparable with that of the PSHA, improves early-stage osteogenic differentiation and osseointegration abilities and has great potential for enhancing the initial stability and long-term survival of uncemented or 3D porous titanium implants.

The morphological effect of nanostructured hydroxyapatite coatings on the osteoinduction and osteogenic capacity of porous titanium.

Weak osteogenic activity affects the long-term fixation and lifespan of titanium (Ti) implants. Surface modification along with a built-in porous structure is a highly considerable approach to improve the osteoinduction and osseointegration capacity of Ti. Herein, the osteoinduction and osteogenic activities of electrochemically deposited (ED) nanoplate-like, nanorod-like and nanoneedle-like hydroxyapatite (HA) coatings (named EDHA-P, EDHA-R, and EDHA-N, respectively) were evaluated in vitro and in vivo by comparison with those of acid/alkali (AA) treatment. The results revealed that the apatite forming ability of all nanostructured EDHA coatings was excellent, and only 12 h of soaking in SBF was needed to induce a complete layer of apatite. More serum proteins adsorbed on EDHA-P than others. In cellular experiments, different from those on EDHA-R and EDHA-N, the cells on EDHA-P presented a polygonal shape with lamellipodia extension, and thus exhibited a relatively larger spreading area. Furthermore, EDHA-P was more favorable for the enhancement of the proliferation and ALP activity of BMSCs, and the up-regulation of OPN gene expression. Based on the good biological performance in vitro, EDHA-P was selected to further evaluate its osteoinduction and osteogenic activities in vivo by comparison with AA treatment. Interestingly, a greater ability of ectopic osteoinduction was observed in the EDHA-P group compared to that in the AA group. At the osseous site, EDHA-P promoted more bone on/ingrowth, and had a higher area percentage of newly formed bone in the bone-implant interface and inner pores of the implants than in the AA group. Thus, a nanoplate-like HA coating has good potential in improving the osteoinductivity and osteogenic activity of porous Ti implants in clinical applications.

The optimized preparation of HA/L-TiO2/D-TiO2 composite coating on porous titanium and its effect on the behavior osteoblasts.

Various surface bioactivation technology has been confirmed to improve the osteogenic ability of porous titanium (pTi) implants effectively. In this study, a three-layered composite coating, i.e. outer layer of hydroxyapatite (HA), middle layer of loose titanium dioxide (L-TiO2) and inner layer of dense TiO2 (D-TiO2), was fabricated on pTi by a combined processing procedure of pickling, alkali heat (AH), anodic oxidation (AO), electrochemical deposition (ED) and hydrothermal treatment (HT). After soaking in simulated body fluid for 48 h, the surface of the AHAOEDHT-treated pTi was completely covered by a homogeneous apatite layer. Using MC3T3-E1 pro-osteoblasts as cell model, the cell culture revealed that both the pTi without surface treatment and the AHAOEDHT sample could support the attachment, growth and proliferation of the cells. Compared to the pTi sample, the AHAOEDHT one induced higher expressions of osteogenesis-related genes in the cells, including alkaline phosphatase, Type I collagen, osteopontin, osteoclast inhibitor, osteocalcin and zinc finger structure transcription factor. As thus, besides the good corrosion resistance, the HA/L-TiO2/D-TiO2-coated pTi had good osteogenic activity, showing good potential in practical application for bone defect repair.

Effects of Nanotopography Regulation and Silicon Doping on Angiogenic and Osteogenic Activities of Hydroxyapatite Coating on Titanium Implant.

BACKGROUND: Angiogenic and osteogenic activities are two major problems with biomedical titanium (Ti) and other orthopedic implants used to repair large bone defects. PURPOSE: The aim of this study is to prepare hydroxyapatite (HA) coatings on the surface of Ti by using electrochemical deposition (ED), and to evaluate the effects of nanotopography and silicon (Si) doping on the angiogenic and osteogenic activities of the coating in vitro. MATERIALS AND METHODS: HA coating and Si-doped HA (HS) coatings with varying nanotopographies were fabricated using two ED modes, ie, the pulsive current (PC) and cyclic voltammetry (CV) methods. The coatings were characterized through scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectrometer (XPS), and atomic force microscopy (AFM), and their in vitro bioactivity and protein adsorption were assessed. Using MC3T3-E1 pre-osteoblasts and HUVECs as cell models, the osteogenic and angiogenic capabilities of the coatings were evaluated through in vitro cellular experiments. RESULTS: By controlling Si content in ~0.8 wt.%, the coatings resulting from the PC mode (HA-PC and HS-PC) and CV mode (HA-CV and HS-CV) had nanosheet and nanorod topographies, respectively. At lower crystallinity, higher ionic dissolution, smaller contact angle, higher surface roughness, and more negative zeta potential, the HS and PC samples exhibited quicker apatite deposition and higher BSA adsorption capacity. The in vitro cell study showed that Si doping was more favorable for enhancing the viability of the MC3T3-E1 cells, but nanosheet coating increased the area for cell spreading. Of the four coatings, HS-PC with Si doping and nanosheet topography exhibited the best effect in terms of up-regulating the expressions of the osteogenic genes (ALP, Col-I, OSX, OPN and OCN) in the MC3T3-E1 cells. Moreover, all leach liquors of the surface-coated Ti disks promoted the growth of the HUVECs, and the HS samples played a more significant role in promoting cell migration and tube formation than the HA samples. Of the four leach liquors, only the two HS samples up-regulated NO content and expressions of the angiogenesis-related genes (VEGF, bFGF and eNOS) in the HUVECs, and the HS-PC yielded a better effect. CONCLUSION: The results show that Si doping while regulating the topography of the coating can help enhance the bone regeneration and vascularization of HA-coated Ti implants.

Cell-Laden Electroconductive Hydrogel Simulating Nerve Matrix To Deliver Electrical Cues and Promote Neurogenesis.

Natural nerve tissue is composed of nerve bundles with multiple aligned assembles, and matrix electroconductivity is beneficial to the transmission of intercellular electrical signals, or effectively deliver external electrical cues to cells. Herein, aiming at the biomimetic design of the extracellular matrix for neurons, we first synthesized electroconductive polypyrrole (PPy) nanoparticles with modified hydrophilicity to improve their uniformity in collagen hydrogel. Next, cell-laden collagen-PPy hybrid hydrogel microfibers with highly oriented microstructures were fabricated via a microfluidic chip. The hydrogel microfibers formed a biomimetic three-dimensional microenvironment for neurons, resulting from the native cell adhesion domains, oriented fibrous structures, and conductivity. The oriented fibrous microstructures enhanced neuron-like cells aligning with fibers' axon; the matrix conductivity improved cell extension and upregulated neural-related gene expression; moreover, external electrical stimulation further promoted the neuronal functional expression. This mechanism was attributed to the electroconductive matrix and its delivered electrical stimulation to cells synergistically upregulated the expression of an L-type voltage-gated calcium channel, resulting in an increase in the intracellular calcium level, which in turn promoted neurogenesis. This approach has potential in constructing the biomimetic microenvironment for neurogenesis.

Scanning tunneling microscopy study of DNA-chromophore motif on solid surfaces.

We focus our studies on DNA-chromophore motif on surfaces using samples prepared by the synthetic methods described by Wang and Li in a recent publication (J. Am. Chem. Soc. 2003, 125, 5248-5249). Scanning tunneling microscope (STM) was used to investigate the DNA-chromophore hybrids adsorbed on Au(111) and highly oriented pyrolytic graphite (HOPG) surfaces at room temperature in air. Experiments found that the DNA-chromophore hybrid molecules easily formed multimolecule aggregations on gold surface. On HOPG surfaces, however, DNA-chromophore hybrids were usually adsorbed as single molecules. STM images further showed DNA-chromophore hybrids adsorbed on Au(111) surfaces existed in the form of single molecule, dimer, trimer, tetramer, etc. The occurrence of molecular aggregations indicates that molecular interactions are comparable or stronger than molecule-substrate interactions; such weak interactions control the geometrical sizes and topographical shapes of the self-assembled DNA-chromophore hybrids on surfaces.

An improved polymeric sponge replication method for biomedical porous titanium scaffolds.

Biomedical porous titanium (Ti) scaffolds were fabricated by an improved polymeric sponge replication method. The unique formulations and distinct processing techniques, i.e. a mixture of water and ethanol as solvent, multiple coatings with different viscosities of the Ti slurries and centrifugation for removing the extra slurries were used in the present study. The optimized porous Ti scaffolds had uniform porous structure and completely interconnected macropores (~365.1µm). In addition, two different sizes of micropores (~45.4 and ~6.2µm) were also formed in the skeleton of the scaffold. The addition of ethanol to the Ti slurry increased the compressive strength of the scaffold by improving the compactness of the skeleton. A compressive strength of 83.6±4.0MPa was achieved for a porous Ti scaffold with a porosity of 66.4±1.8%. Our cellular study also revealed that the scaffolds could support the growth and proliferation of mesenchymal stem cells (MSCs).

Construction of surface HA/TiO2 coating on porous titanium scaffolds and its preliminary biological evaluation.

A simple approach to fabricating hydroxyxapatite/titanium dioxide (HA/TiO2) coating on porous titanium (Ti) scaffolds was developed in the present study. Surface TiO2 layer was firstly formed on porous Ti scaffolds with multi-scale pores by acid-alkali (AA) treatment. The outer HA layer was then formed on the TiO2 layer by subsequent pulse electrochemical deposition (ED) technique. All the three main process parameters, i.e. deposition times, current density and mass transfer mode affected the properties of the HA coating notably. Under the conditions of 90 deposition cycles, -10mA/cm2 of pulse current density and stirring, a thin layer of homogeneous and nanorod-like HA sediments was formed on the substrate surface of porous Ti scaffolds. The results of protein adsorption and cellular experiments showed that compared to the single TiO2 surface, the HA/TiO2 surface allowed more adsorption of serum proteins and further enhanced the alkaline phosphatase (ALP) activity of MC3T3-E1 osteoblasts.

Bone regeneration with micro/nano hybrid-structured biphasic calcium phosphate bioceramics at segmental bone defect and the induced immunoregulation of MSCs.

Adequate bone regeneration has been difficult to achieve at segmental bone defects caused by disease. The surface structure and phase composition of calcium phosphate bioceramic are crucial for its bioactivity and osteoinductivity. In the present study, biphasic calcium phosphate (BCP) bioceramics composed of micro-whiskers and nanoparticles hybrid-structured surface (hBCP) were fabricated via a hydrothermal reaction. The in vivo long bone defect model of beagle dogs implanted with hBCP bioceramics achieved a higher quality regenerated bone as compared to the traditional smooth-surface BCP control group. After a 12-week implantation period, more new bone formation within the implanted material and a higher fracture load were observed in the hBCP group (p < 0.05 vs. control). In addition, the local bone integration efficacy, as determined by nanoindentation, showed a significantly closer elastic modulus of the implanted hBCP bioceramics to that of the natural bone adjacent. Finally, in vitro gene microarray analysis of the mesenchymal stem cells (MSCs) co-cultured with two bioceramics showed that the hBCP group induced a drastic downregulation of the genes associated with inflammatory response, which was never documented in previous studies regarding biomaterials with a micro/nano hybrid structure. The tumor necrosis factor (TNF) signalling pathway was the most involved and preferentially inhibited by the hBCP material. Collectively, the findings suggested that the micro/nano hybrid-structured bioceramics augmented local bone regeneration at segmental bone defects and presented a potential alternative to autologous bone grafts.

Effects of long-term cattle manure application on soil properties and soil heavy metals in corn seed production in Northwest China.

To evaluate the effects of manure application on continuous maize seed production, 10-year cattle manure on soil properties, heavy metal in soil and plant were evaluated and investigated in calcareous soil. Results showed that manure application increased soil organic matter, total and available nutrients, pH, and electrical conductivity (EC), and the most massive rate caused the highest increase. Manure application led to an increase in exchangeable fraction and an increase of availability of heavy metal. Residual fraction was dominant among all metals, followed by the fraction bound to Fe and Mn oxides. Manure application involved accumulation of heavy metal on corn, but the accumulation in the stem is higher than that in the seed. Manure application led to a high deficiency of total Zn and high accumulation of total Cd in the soil of corn seed production, which should be a risk for safety seed production in calcareous soil in Northwest China.