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.

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.

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.

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.

Biological and antibacterial properties of plasma sprayed wollastonite/silver coatings.

In this work, plasma sprayed wollastonite/silver coatings were prepared to obtain an implant material having excellent bioactivity, cytocompatibility as well as antibacterial property. The surface characteristics of wollastonite/silver coating were investigated by scanning electron microscopy, energy dispersive spectrometer, atomic absorbance spectroscope and x-ray diffraction. The bioactivity was examined by simulated body fluid soaking test. The antibacterial activity against Escherichia coli was examined by bacterial counting method. And the cytocompatibility and in vitro osteotoxicity was evaluated by alamarBlue Assay using MG-63 osteoblasts. The results showed that silver existed in the wollastonite coating homogeneously as silver oxide and metal silver, which ensured a sustained release of silver for 28 days in deionized water. The loaded silver showed strong inhibition against the growth of Escherichia coli, however exhibited no osteotoxicity. Although the wollastonite/silver coating can not induce apatite formation as quickly as the wollastonite coating did in simulated body fluid, it still exhibited good bioactivity. Therefore, the plasma sprayed wollastonite/silver coating is a promising implant material to be applied in surgery, reducing postoperative infections.

Influences of ionic dissolution products of dicalcium silicate coating on osteoblastic proliferation, differentiation and gene expression.

This work aims to explore the influence of the ionic products of dicalcium silicate coating on osteoblastic proliferation and differentiation, as well as on the expression of BMP2 and its signal transducers Smad1, 6 and 7 in MG-63 osteoblast-like cells. Plasma-sprayed dicalcium silicate coatings were soaked in DMEM to obtain culture media containing the ionic dissolution products of dicalcium silicate coating (Ca2SiO4-DMEM). MG63 osteoblast-like cells were cultured in Ca2SiO4-DMEM (experimental group) for 3-12 days, while those cultured in normal DMEM served as control (control group). MTT assay was used to evaluate cell viability and proliferation. Alkaline phosphatase activity (ALP), osteocalcin (OC) and type I collagen (COLI) were investigated as differentiation markers. Gene expression of BMP2 and Smad1, 6, 7 was also detected. BMP2 protein was examined by ELISA assay. Alizarin Red-S (AR-S) assay was used to detect mineralization. The results demonstrated that Si concentration in Ca2SiO4-DMEM is markedly higher than that in normal DMEM. Compared to the control group, MG63 cells of the experimental group exhibited upregulated proliferation on day 3, and markedly upregulated gene expression of the differentiation markers, especially on days 9 and 12 for OC and on days 3, 6 and 9 for ALP. Gene expression of BMP2 and Smad1, as well as BMP2 protein secreted into culture media, was also upregulated in the experimental group, while gene expression of Smad6 and 7 was not influenced. AR-S assay indicated a higher calcium mineral content deposition in cells of the experimental group. In conclusion, the ionic products of plasma-sprayed dicalcium silicate coating are beneficial to the proliferation and differentiation of MG63 osteoblast-like cells.

[Primary study on the antibacterial property of silver-loaded nano-titania coatings].

OBJECTIVE: To study the preparation and characteristics of silver-loaded nano-titania coating so as to develop a bioactive implant material with antibacterial property. METHODS: Plasma sprayed nano-titania coatings were immersed in 1%, 5%, and 9% AgNO3 solution to load silver. The loaded silver and its distribution were evaluated by scanning electron microscopy (SEM) and energy dispersive spectrometer (EDS). After optimizing the preparation process, the release rate of silver from the nano-titania coating was measured in deionized water, its corresponding in vitro cytotoxicity and antibacterial activity were also examined. RESULTS: The loaded silver was in proper quantity and distributed evenly on the nano-titania coatings after immersion in 5% AgNO3. A burst release of the silver could be detected. The quick release of silver from the titania coatings sustained about 12 days in deionized water, which had no obvious influence on the surface morphology of titania coatings. The loaded silver did not inhibit the osteoblast proliferation (P = 0.1) and alkaline phosphatase expression (P = 0.06), however, it effectively inhibited the survival and growth of Staphylococcus aureus for 12 days: the zone of inhibition reached 3.81 +/- 0.8 mm with a bacteria killing rate of 100%. CONCLUSIONS: It is economical and effective to prepare the silver-loaded nano-titania coatings by 5% AgNO3 solution. The loaded silver has good antibacterial function, and shows no obvious effect on the physical and biological properties of nano-titania coatings.

[In vitro comparison of antibacterial properties of plasma sprayed wollastonite coatings loading silver and gentamicin].

OBJECTIVE: To develop antibacterial coatings for orthopedic implants with a sustained release of drugs. METHODS: Wollastonite coatings were deposited on the titanium substrates by an atmospheric plasma spray system. After soaking in weight percent of 5% AgNO(3) solution for 24 h, the wollastonite coatings loading silver were obtained. Gentamicin were loaded on the wollastonite coatings by collagen grafting process. The release rates of drugs from wollastonite coatings were investigated by the in vitro solution soaking test. One strain of S. aureus was used in zone of inhibition test to evaluate the antibacterial properties of drug loaded wollastonite coatings, and the cell culture test was used to evaluate their cytotoxicity. RESULTS: Silver and gentamicin loaded wollastonite coatings were successfully prepared. The release of silver ions from the silver loaded wollastonite coatings lasted 50 d in deionized water, effectively inhibiting the growth of S. aureus for 40 d. While an initial burst release of gentamicin was found during the in vitro solution soaking test. The gentamicin released from gentamicin loaded wollastonite coatings can inhibit the growth of S. aureus for 18 d. Both the two kinds of antibacterial wollastonite coatings showed no adverse effect on cellular adhesion, proliferation and alkaline phosphatase expression. CONCLUSIONS: Compared with gentamicin loaded wollastonite coatings, silver loaded wollastonite coatings may have more promising clinical applications due to the even and long-time antibacterial agent release.