Smart Implant with Bacteria Monitoring and Killing Ability for Orthopedic Applications.

Bacterial infections around implants constitute a significant cause of implant failures. Early recognition of bacterial adhesion is an essential factor in preventing implant infections. Therefore, an implant capable of detecting and disinfecting initial bacterial adhesion is required. This study reports on the development of an intelligent solution for this issue. We developed an implant integrated with a biosensor electrode based on alternating current (AC) impedance technology to monitor the early growth process of Escherichia coli (E. coli) and its elimination. The biosensor electrode was fabricated by coating polypyrrole (PPy) doped with sodium p-toluenesulfonate (TSONa) on titanium (Ti) surfaces. Monitoring the change in resistance using electrochemical impedance spectroscopy (EIS), combined with an equivalent circuit model (ECM), enables the monitoring of the early adhesion of E. coli. The correlation with the classical optical density (OD) monitoring value reached 0.989. Subsequently, the eradication of bacteria on the electrode surface was achieved by applying different voltages to E. coli cultured on the electrode surface, which caused damage to E. coli. Furthermore, in vitro cellular experiments showed that the PPy coating has good biocompatibility and can promote bone differentiation.

Metallic Nanoparticle-Doped Oxide Semiconductor Film for Bone Tumor Suppression and Bone Regeneration.

Bone implants with the photothermal effect are promising for the treatment of bone tumor defects. Noble metal-based photothermal nanoagents are widely studied for their stable photothermal effect, but they are expensive and difficult to directly grow on implant surfaces. In contrast, non-noble metal photothermal nanoagents are economical but unstable. Herein, to develop a stable and economical photothermal film on bone implants, a Ni nanoparticle-doped oxide semiconductor film was grown in situ on Nitinol via the reduction of Ni-Ti-layered double hydroxides. Ni nanoparticles remained stable in the NiTiO3 structure even when immersed in fluid for 1 month, and thus, the film presented a reliable photothermal effect under near-infrared light irradiation. The film also showed excellent in vitro and in vivo antitumor performance. Moreover, the nanostructure on the film allowed bone differentiation of mouse embryo cells (C3H10T1/2), and the released Ni ions supported the angiogenesis behavior of human vein endothelial cells. Bone implantation experiments further showed the enhancement of osteointegration of the modified Nitinol implant in vivo. This novel multifunctional Nitinol bone implant design offers a promising strategy for the therapy of bone tumor-related defects.

Porous thermosensitive coating with water-locking ability for enhanced osteogenic and antibacterial abilities.

Preferable antibacterial property and osteogenesis are the permanent pursuit for metallic implants. However, it is difficult to satisfy both the properties. In fact, implants may be contaminated with bacteria during storage and surgery, leading to inflammation. Therefore, the antibacterial property of biomaterial surfaces is required not only in the human environment but also at room temperature. In this study, porous structures loaded with a thermosensitive poly (N-isopropylacrylamide) (PNIPAM) hydrogel on a nitinol (NiTi) substrate were constructed. When the temperature is 25 â€‹°C, almost all bacteria cannot adhere to the sample surface due to the abundant hydration layer of the PNIPAM hydrogel. Meanwhile, when the temperature is 37 â€‹°C, the structure of the PNIPAM hydrogel collapses and the hydration layer disappears due to the temperature change. However, the porous structures lock water in the pores, which results in a high-hydration-rate sample surface. This surface has few bacterial adhesion sites; nevertheless, the adhesion of larger cells to the surface is not impeded by the porous structure. In addition, the PNIPAM hydrogel is soft and biocompatible, so the sample can have better cell adhesion and proliferation than a bare NiTi alloy. Based on these results, it can be concluded that the porous NiTi sample loaded with the thermosensitive PNIPAM hydrogel has the antibacterial property before implantation and the dual function of inhibiting bacterial adhesion and promoting cell adhesion and proliferation after implantation, which shows promising applications in the biomedical field such as orthopedic implantation.

Strontium-Containing Barium Titanate-Modified Titanium for Enhancement of Osteointegration.

One of the major challenges for Ti-based implants is insufficient osteointegration, which might result in the loosening of the implant. In this study, we fabricated strontium (Sr)-containing barium titanate (BST) on the surface of Ti to improve the bioactivity for osteointegration enhancement. The introduction of Sr significantly reduced the crystallization time and improved crystallinity, which was proved by X-ray diffraction, X-ray photoelectron spectroscopy, and transmission electron microscopy. Compared with Ti, the BST film showed greater wettability surface and lower elastic modulus and hardness. Furthermore, in synergy with the release of Sr ions, the BST film improved early adhesion and followed osteogenic differentiation of rat bone mesenchymal stem cells. Furthermore, the bone implantation experiment suggested that the BST film could significantly improve the in vivo osteogenesis and osteointegration capabilities of Ti implants. In summary, this study revealed that BST-modified Ti has potential application in bone repair.

Mg-Fe layered double hydroxides modified titanium enhanced the adhesion of human gingival fibroblasts through regulation of local pH level.

The durability of dental implants is closely related to osseointegration and surrounding soft tissue sealing. Appropriate local pH favors fibroblasts adhesion and contributes to soft tissue sealing. Layered double hydroxides (LDHs) are characterized by adjustable alkalinity, offering a possibility to investigate the influence of pH on cellular behaviors. Herein, we fabricated MgFe LDHs modified titanium. During calcination, the local pH value of LDHs increase, without altering other physics and chemical properties via OH- exchange mechanism. In vitro studies showed that LDHs films calcined at 250 °C for 2 h provide a local pH of 10.17, which promote early adhesion, proliferation, and type I collagen expression of human gingival fibroblasts (hGFs) through the formation of focal adhesion complex and activation of focal adhesion kinase related signaling pathways. In conclusion, endowing the titanium surface with appropriate alkalinity by MgFe LDHs films enhances the adhesion of hGFs, providing a new strategy of designing multifunctional biomaterials for soft tissue sealing around dental implants.

Thermosensitive -hydrogel-coated titania nanotubes with controlled drug release and immunoregulatory characteristics for orthopedic applications.

Although Ti is widely used in orthopedic implants, its bio-inert characteristics and poor antibacterial activity may result in implant failure. To counter this problem, in this study, we loaded simvastatin, a bioactive compound that promotes osteogenesis, in TiO2 nanotubes and a thermosensitive chitosan-glycerin-hydroxypropyl methyl cellulose hydrogel (CGHH) was then layered on top of these nanotubes. At normal human-body temperature (37 °C), CGHH was present in a sol state, thus facilitating the controlled release of simvastatin to enhance differentiation in MC3T3-E1 osteoblasts. In vitro cell-culture studies suggested that CGHH in a gel state would induce macrophage polarization to the pro-inflammatory M1 phenotype. In vitro testing against Escherichia coli and Staphylococcus aureus indicated no antibacterial activity in CGHH in both sol and gel states. However, the results of subcutaneous infection animal models suggested that CGHH showed excellent in vivo antibacterial activity, which can be explained by the fact at high temperatures induced by an infection, CGHH transitioned into a gel state and released large amounts of glycerin. Such a high glycerin dosage induced an acute inflammatory reaction and antibacterial activity. Thus, due to their enhanced osteogenesis capacity at normal body temperature and antibacterial characteristics in the presence of infection, the newly designed simvastatin-loaded CGHH-encapsulated TiO2 nanotubes are promising materials for application in orthopedic implants.

Paclitaxel-loaded lignin particle encapsulated into electrospun PVA/PVP composite nanofiber for effective cervical cancer cell inhibition.

Electrospun composite nanofibrous scaffolds have been regarded as a potential carrier for local drug delivery to prevent tumor recurrence. Herein, a model drug (paclitaxel) was creatively loaded into lignin nanoparticles (PLNPs) and then encapsulated into the polymer of poly (vinyl alcohol)/polyvinyl pyrrolidone which has been fabricated into a composite nanofibrous membrane (PVA/PVP-PLNPs) for use as a drug carrier using the electrospinning technique. The fabricated PVA/PVP-PLNPs membranes exhibited good particle distribution, mechanical properties, thermal stability and biocompatibility. In vitro experiments showed that combining lignin nanoparticles by electrospinning not only improved the drug release profile, but also enhanced the hydrophilicity of nanofibrous membranes which was beneficial to cell adhesion and proliferation. Cellular experiments demonstrated that PVA/PVP-2%PLNPs membrane showed good cell inhibition ability, and the cell survival rate was only 21% at day 7. It indicates that the as-prepared PVA/PVP-PLNPs composite nanofibers are promising candidates for local anticancer therapy.

Carbon nanotube-collagen@hydroxyapatite composites with improved mechanical and biological properties fabricated by a multi in situ synthesis process.

A novel carbon nanotube-collagen@hydroxyapatite (CNT-Col@HA) composite with good mechanical and biological properties was fabricated successfully by a multi in situ synthesis process, which can be used to repair or replace the damaged bone tissues. The carbon nanotube (CNT)/hydroxyapatite (HA) composite powders were firstly synthesized by the in situ chemical vapor deposition method. After the acidification of CNTs, the collagen (Col) molecules were covalently grafted onto the surface of CNTs in situ by the formation of amide linkages, obtaining Col-encapsulated CNTs powders. And then, a HA layer was deposited in situ onto the Col-encapsulated CNTs to form HA- and Col-encapsulated CNTs, consequently the ideal CNT-Col@HA composite was fabricated by the powder metallurgy method, and its mechanical and biological properties were investigated. The results showed that, the multi in situ synthesis process ensured the homogeneous dispersion of CNTs in HA matrix, and via the intermediate layer of Col, the close chemical bonding between CNT reinforcements and HA matrix was obtained, thereby the flexural strength and fracture toughness of the in situ synthesized 3 wt.% CNT-Col@HA composite were increased by approximately 74.2% and 274.6% compared with those of pure HA bulk, and better cell adhesion, spreading and proliferation were also observed on the in situ synthesized CNT-Col@HA composites. Therefore, the obtained composites in this work have great potential to be applied as implant material in clinic.

Biological and antibacterial properties of TiO2 coatings containing Ca/P/Ag by one-step and two-step methods.

The porous TiO2 coatings containing Ca/P/Ag were separately prepared on titanium (Ti) surface by one-step (micro-arc oxidation) and two-step methods (micro-arc oxidation and cathodic deposition), and then their surface morphology, composition, biological and antibacterial properties were compared. The results showed that the porous coatings containing Ca/P/Ag achieved by different methods showed similar surface morphology and elemental composition, however, by one-step method, silver existed in the coating as silver phosphate, while in the coatings prepared by two-step method, silver existed as metallic silver. Although both coatings showed excellent antibacterial property (the antimicrobial rate is over 99.9%), the surface coating prepared by one-step method had a more suitable release curve of Ag. In addition, the surface coating prepared by one-step method also presented better biological property, which was due to its enhanced surface roughness and hydrophilicity. Combining with its easy operation and long-term antibacterial property, its prospect for clinical application is more promising.

Biological and antibacterial properties of the micro-nanostructured hydroxyapatite/chitosan coating on titanium.

Titanium (Ti) is the widely used implant material in clinic, however, failures still frequently occur due to its bioinertness and poor antibacterial property. To improve the biological and antibacterial properties of Ti implants, micro-nanostructured hydroxyapatite (HA) coating was prepared on Ti surface by micro-arc oxidation (MAO), and then the antibacterial agent of chitosan (CS) was loaded on the HA surface through dip-coating method. The results showed that the obtained HA/CS composite coating accelerated the formation of apatite layer in SBF solution, enhanced cell adhesion, spreading and proliferation, and it also inhibited the bacterial growth, showing improved biological and antibacterial properties. Although, with the increased CS amount, the coverage of HA coating would be enlarged, resulting in depressed biological property, however, the antibacterial property of the composite coating was enhanced, and the cytotoxicity about CS was not detected in this work. In conclusion, the HA/CS coating has promising application in orthopedics, dentistry and other biomedical devices.

Preparation of BMP-2/chitosan/hydroxyapatite antibacterial bio-composite coatings on titanium surfaces for bone tissue engineering.

In this paper, petaling hydroxyapatite (HA)/TiO2 composite coatings were firstly prepared on titanium (Ti) surface by one-step micro-arc oxidation (MAO), and then pure chitosan (CS) and bone morphogenic protein-2 (BMP-2)-encapsulated CS coatings were respectively loaded on the HA/TiO2 surfaces by dip-coating method to endow Ti with good antibacterial and biological properties. The bonding strength between coatings was studied by scratch method. The degradability of CS, BMP-2 release behavior, bioactivity, biocompatibility and antibacterial activity of the obtained (BMP-2)/CS/HA/TiO2 coatings were examined by in vitro tests. The results showed that, the thicker the HA layer, the larger the loaded BMP-2 and CS amount, resulting in better bonding strength between coatings, antibacterial activity and biocompatibility. In addition, with the increase of CS concentration, more CS was loaded on HA coatings, which benefited the increase of CS degrading amount, the prolonged CS degradation time and BMP-2 release time, resulting in improved antibacterial and biological property. All CS/HA/TiO2 coatings accelerated cell adhesion, spreading and proliferation, and promoted HA formation in simulated body fluids (SBF). After loading BMP-2 in CS, the BMP-2 can significantly improve cell adhesion, spreading and proliferation, and the loaded amount can also be controlled by the concentration of BMP-2 solution. The present study indicates that, by controlling the thickness of HA layers and concentrations of CS and BMP-2 solutions, the Ti implant material with excellent biological and antibacterial properties can be achieved.

A Novel Hierarchically Porous Polypyrrole Sphere Modified Separator for Lithium-Sulfur Batteries.

The commercialization of Lithium-sulfur batteries was limited by the polysulfide shuttle effect, and modifying the routine separator was an effective method to solve this problem. In this work, a novel hierarchically porous polypyrrole sphere (PPS) was successfully prepared by using silica as hard-templates. As-prepared PPS was slurry-coated on the separator, which could reduce the polarization phenomenon of the sulfur cathode, and efficiently immobilize polysulfides. As expected, high sulfur utilization was achieved by suppressing the shuttle effect. When tested in the lithium-sulfur battery, it exhibited a high capacity of 855 mAh·g-1 after 100 cycles at 0.2 C, and delivered a reversible capacity of 507 mAh·g-1 at 3 C, showing excellent electrochemical performance.

Self-adjusting antibacterial properties of Ag-incorporated nanotubes on micro-nanostructured Ti surfaces.

Titanium (Ti) is a widely used implant material in clinics; however, failures still frequently occur due to its bioinertness and poor antibacterial capability. Post-implant infections most likely occur within the first two weeks. Thereafter, the host immune system lowers the infection risk, and biosafety becomes the first consideration. Therefore, endowing biomedical Ti with a time-dependent bactericidal effect is of considerable interest. In this study, Ag nanoparticles (NPs) as the antibacterial agent were incorporated deeply into TiO2 nanotubes prepared on the sandblasted and etched (SLA) Ti surface. The incorporated Ag NPs were verified to automatically transform from a free state to an immobilized state, rendering the constructed platform exhibit a self-adjusting antibacterial effect. It showed strong "release bactericidal" activity in the early phase that gradually changed to the "contact bactericidal" ability. Such a smart alteration could satisfy the varied antibacterial requirements in different periods after biomaterial implantation. Moreover, the nanotubular structure could accelerate apatite formation and improve cell adhesion and proliferation when compared with those of commercially used SLA implants. Based on these results, it can be concluded that Ag-NP-incorporated micro-nanostructured Ti has worthwhile biological and time-dependent antibacterial properties, and it can have promising applications in orthopedics, dentistry, and fabrication of other biomedical devices.

Synthesis and Characterization of Flower-like Carbon-encapsulated Fe-C Nanoparticles for Application as Adsorbing Material.

Carbon-encapsulated Fe-C (Fe-C@C) nanoparticles with a divergently flower-like morphology were successfully synthesized for application as an adsorbing material by using freeze-drying and chemical vapor deposition (CVD) methods. The Fe metallic source was first loaded onto a sodium chloride (NaCl) supporter via freeze-drying to obtain the Fe/NaCl composite powder. Then, Fe-C@C nanoparticles were synthesized in the temperature range of 300⁻450 °C via CVD of acetylene in the Fe/NaCl composite powder using Fe nanoparticles as catalysts and NaCl as supporters. Because the NaCl supporter is water-soluble, the synthesized Fe-C@C nanoparticles were easy to purify, and a high purity was obtained by simple washing and centrifugation. The optimal Fe-C@C nanoparticles, synthesized at 400 °C, possessed a unique divergently flower-like structure and a high specific surface area of 169.4 m²/g that can provide more adsorption sites for contaminants. Adsorption experiments showed that the flower-like Fe-C@C adsorbent exhibited high adsorption capacity (90.14 mg/g) and fast removal of methylene blue (MB). Moreover, the magnetic properties of the nanoparticles, with saturation magnetization of 36.544 emu/g, facilitated their magnetic separation from wastewater. Therefore, the novel flower-like Fe-C@C nanoparticles with integrated adsorptive and magnetic properties have the potential to be an effective adsorbent in dye wastewater treatment.

Preparation and properties of carbon nanotube (Fe)/hydroxyapatite composite as magnetic targeted drug delivery carrier.

A novel magnetic targeted drug delivery carrier based on a carbon nanotube (Fe)/hydroxyapatite (CNT(Fe)/HA) composite was successfully fabricated by an in situ synthesis of CNTs in HA nanopowder using Fe catalysts and subsequent chemical modification of the as-fabricated CNT(Fe)/HA by chitosan (CS) and folic acid (FA) for a controllable release of an anticancer drug doxorubicin (DOX). The synthesized CNTs, Fe, and HA self-assembled into a composite structure in situ during the synthesis. After the acid treatment, the CNTs were shorter and homogeneously dispersed, the tips of the CNTs were opened, and oxygen-containing functional groups were introduced onto the CNTs. Upon the functional modification through the surface coating with CS and FA, the functionalized CNT(Fe)/HA became capable of loading DOX through both π-π stacking and electrostatic adsorption of FA. The results showed that the average drug-loading rate of DOX was 130 wt%. Furthermore, the pH response of FA-CS-CNT(Fe)/HA enabled the release of a large amount of DOX in phosphate-buffered saline (PBS) at pH = 5.5 with an average drug release rate of 52 wt% after 72 h. In contrast, the drug release in PBS at pH = 7.4 was only 8 wt%. In addition, the saturation magnetization, coercive force, and remanence to saturation magnetization ratio of DOX-FA-CS-CNT(Fe)/HA were 0.88 emu g-1, 668.96 Oe, and 0.44, respectively, indicating its potential for drug transport under strong external magnetic fields, which could enable magnetic targeted delivery.

Improved osteoblast adhesion and osseointegration on TiO2 nanotubes surface with hydroxyapatite coating.

To improve initial osteoblast adhesion and subsequent osseointegration, TiO2 nanotubes layer was constructed on the titanium (Ti) surface by anodic oxidation (AO), with an additional hydroxyapatite (HA) coating to form the AO/HA surface. Tests on in vitro cellular activity displayed that the AO surface, especially the AO/HA surface, promoted initial adhesion, proliferation and differentiation of osteoblast cells. The modified AO and AO/HA surfaces further presented an up-regulated gene expression of osteogenic and adhesion markers collagen type 1 (COL), osteopontin (OPN), osteocalcin (OCN) and vinculin. In addition, in vivo experiments with a rat model demonstrated that the AO surface, particularly the AO/HA surface, achieved earlier osseointegration and a superior bone bonding ability compared with Ti. Our study shed light on a synergistic role played by nanotopography and HA in promoting osteoblast adhesion, proliferation, differentiation and osseointegration, thus suggesting a promising method for better modifying the implant surface.

Carbon nanotube-reinforced mesoporous hydroxyapatite composites with excellent mechanical and biological properties for bone replacement material application.

Carbon nanotube (CNT)-reinforced mesoporous hydroxyapatite (HA) composites with excellent mechanical and biological properties were fabricated successfully by the in situ chemical deposition of mesoporous HA on homogeneously dispersed CNTs. The CNTs are first synthesized in situ on HA nanopowders by chemical vapor deposition, and then, the HA particles with mesoporous structures are deposited in situ onto the as-grown CNTs by using cetyl trimethyl ammonium bromide as templates to form mesoporous HA encapsulated CNTs (CNT@meso-HA). The modification of CNTs by mesoporous HA leads to strong CNT-HA interfacial bonding, resulting in efficient load transfer between CNT and HA and improved mechanical properties of CNT/HA composites. More importantly, the mesoporous HA structure has a high specific surface area and large surface roughness that greatly promote the cell adhesion and proliferation, resulting in better biocompatibility and improved osteoblast viability (MC3T3-E1) compared to those fabricated by traditional methods. Therefore, the obtained CNT@meso-HA composites are expected to be promising materials for bone regeneration and implantation applications.

Biological and Mechanical Effects of Micro-Nanostructured Titanium Surface on an Osteoblastic Cell Line In vitro and Osteointegration In vivo.

Hybrid micro-nanostructure implant surface was produced on titanium (Ti) surface by acid etching and anodic oxidation to improve the biological and mechanical properties. The biological properties of the micro-nanostructure were investigated by simulated body fluid (SBF) soaking test and MC3T3-E1 cell co-culture experiment. The cell proliferation, spreading, and bone sialoprotein (BSP) gene expression were examined by MTT, SEM, and reverse transcription-polymerase chain reaction (RT-PCR), respectively. In addition, the mechanical properties were evaluated by instrumented nanoindentation test and friction-wear test. Furthermore, the effect of the micro-nanostructure surface on implant osteointegration was examined by in vivo experiment. The results showed that the formation of bone-like apatite was accelerated on the micro-nanostructured Ti surface after immersion in simulated body fluid, and the proliferation, spreading, and BSP gene expression of the MC3T3-E1 cells were also upregulated on the modified surface. The micro-nanostructured Ti surface displayed decreased friction coefficient, stiffness value, and Young's modulus which were much closer to those of the cortical bone, compared to the polished Ti surface. This suggested much better mechanical match to the surrounding bone tissue of the micro-nanostructured Ti surface. Furthermore, the in vivo animal experiment showed that after implantation in the rat femora, the micro-nanostructure surface displayed higher bonding strength between bone tissues and implant; hematoxylin and eosin (H&E) staining suggested that much compact osteoid tissue was observed at the interface of Micro-nano-Ti-bone than polished Ti-bone interface after implantation. Based on these results mentioned above, it was concluded that the improved biological and mechanical properties of the micro-nanostructure endowed Ti surface with good biocompatibility and better osteointegration, implying the enlarged application of the micro-nanostructure surface Ti implants in future.

Improvement of biological and mechanical properties of titanium surface by anodic oxidation.

A homogeneous and uniform array of nanotubes with a diameter of about 70 nm was produced on titanium (Ti) surface by anodic oxidation. The wall thickness of the nanotubes was around 20 nm, and the depth was about 200 nm. The biological properties of the anodized Ti surface were investigated by simulated body fluid (SBF) soaking test and in vitro cell culture test. The mechanical properties were evaluated by instrumented nanoindentation test and friction-wear test. The results showed that the anodized Ti surface can induce the formation of bone-like apatite after immersion in SBF for four weeks, enhance cell adhesion, proliferation and gene expression, it also showed decreased friction coefficient, similar stiffness and Young's modulus to those of the cortical bone. Based on these results, it can be concluded that anodic oxidation endowed the Ti surface with improved biological and mechanical properties, which was attributed to the formation of nanostructured surface.

Fabrication and Properties of Carbon-Encapsulated Cobalt Nanoparticles over NaCl by CVD.

Carbon-encapsulated cobalt (Co@C) nanoparticles, with a tunable structure, were synthesized by chemical vapor deposition using Co nanoparticles as the catalyst and supported on a water-soluble substrate (sodium chloride), which was easily removed by washing and centrifugation. The influences of growth temperature and time on the structure and magnetic properties of the Co@C nanoparticles were systematically investigated. For different growth temperatures, the magnetic Co nanoparticles were encapsulated by different types of carbon layers, including amorphous carbon layers, graphitic layers, and carbon nanofibers. This inferred a close relationship between the structure of the carbon-encapsulated metal nanoparticles and the growth temperature. At a fixed growth temperature of 400 °C, prolonged growth time caused an increase in thickness of the carbon layers. The magnetic characterization indicated that the magnetic properties of the obtained Co@C nanoparticles depend not only on the graphitization but also on the thickness of the encapsulated carbon layer, which were easily controlled by the growth temperatures and times. Optimization of the synthesis process allowed achieving relatively high coercivity of the synthesized Co@C nanoparticles and enhancement of its ferromagnetic properties, which make this system promising as a magnetic material, particularly for high-density magnetic recording applications.