Incorporation of heparin/BMP2 complex on GOCS-modified magnesium alloy to synergistically improve corrosion resistance, anticoagulation, and osteogenesis.

The in vivo fast degradation and poor biocompatibility are two major challenges of the magnesium alloys in the field of artificial bone materials. In this study, graphene oxide (GO) was first functionalized by chitosan (GOCS) and then immobilized on the magnesium alloy surface, finally the complex of heparin and bone morphogenetic protein 2 was incorporated on the modified surface to synergistically improve the corrosion resistance, anticoagulation, and osteogenesis. Apart from an excellent hydrophilicity after the surface modification, a sustained heparin and BMP2 release over 14 days was achieved. The corrosion resistance of the modified magnesium alloy was significantly better than that of the control according to the results of electrochemical tests. Moreover, the corrosion rate was also significantly reduced in contrast to the control. The modified magnesium alloy not only had excellent anticoagulation, but also can significantly promote osteoblast adhesion and proliferation, upregulate the expression of alkaline phosphatase and osteocalcin, and enhance mineralization. Therefore, the method of the present study can be used to simultaneously improve the corrosion resistance and biocompatibility of the magnesium alloys targeted for the orthopedic applications.

A CO-releasing coating based on carboxymethyl chitosan-functionalized graphene oxide for improving the anticorrosion and biocompatibility of magnesium alloy stent materials.

Due to its biofunctions similar to NO, the CO gas signaling molecule has gradually shown great potential in cardiovascular biomaterials for regulating the in vivo performances after the implantation and has received increasing attention. To construct a bioactive surface with CO-releasing properties on the surface of magnesium-based alloy to augment the anticorrosion and biocompatibility, graphene oxide (GO) was firstly modified using carboxymethyl chitosan (CS), and then CO-releasing molecules (CORM401) were introduced to synthesize a novel biocompatible nanomaterial (GOCS-CO) that can release CO in the physiological environments. The GOCS-CO was further immobilized on the magnesium alloy surface modified by polydopamine coating with Zn2+ (PDA/Zn) to create a bioactive surface capable of releasing CO in the physiological environment. The outcomes showed that the CO-releasing coating can not only significantly enhance the anticorrosion and abate the corrosion degradation rate of the magnesium alloy in a simulated physiological environment, but also endow it with good hydrophilicity and a certain ability to adsorb albumin selectively. Owing to the significant enhancement of anticorrosion and hydrophilicity, coupled with the bioactivity of GOCS, the modified sample not only showed excellent ability to prevent platelet adhesion and activation and reduce hemolysis rate but also can promote endothelial cell (EC) adhesion, proliferation as well as the expression of nitric oxide (NO) and vascular endothelial growth factor (VEGF). In the case of CO release, the hemocompatibility and EC growth behaviors were further significantly improved, suggesting that CO molecules released from the surface can significantly improve the hemocompatibility and EC growth. Consequently, the present study provides a novel surface modification method that can simultaneously augment the anticorrosion and biocompatibility of magnesium-based alloys, which will strongly promote the research and application of CO-releasing bioactive coatings for surface functionalization of cardiovascular biomaterials and devices.

[Effects of extracellular matrix protein micropatterns on osteoblast cell adhesion and spreading].

The main purpose of the present study was to investigate the cell behaviors of rat primary osteoblast cells on extracellular matrix (ECM) protein micropatterns. For this purpose, a series of fibronectin micropatterns with different shapes and varying dimensions were created on polystyrene (PS) surfaces by microcontact printing. The results of confocal laser scanning microscopy (CLSM) images indicated that excellent micropatterns were successfully obtained. These protein patterns were stable during the cell culture. The cell experiments suggested that the osteoblast cells preferentially attached onto protein-functionalized areas and displayed different cell shape and spreading behavior on different protein micropatterns. The protein micropatterns can significantly influence the cell adhesion, spreading, alignment and orientation and so on. Therefore, this work can be used to modify biomaterial surfaces, especially that of bone-implant biomaterials, to effectively control cell behavior. It further contributes to clarify the interfacial biological behaviors between biomaterials and osteoblast and can provide the cues for development of bone implantable materials which is able to modulate osteoblast cell growth behavior.

Fabrication of CO-releasing surface to enhance the blood compatibility and endothelialization of TiO2 nanotubes on titanium surface.

Although the construction of nanotube arrays with the micro-nano structures on the titanium surfaces has demonstrated a great promise in the field of blood-contacting materials and devices, the limited surface hemocompatibility and delayed endothelial healing should be further improved. Carbon monoxide (CO) gas signaling molecule within the physiological concentrations has excellent anticoagulation and the ability to promote endothelial growth, exhibiting the great potential for the blood-contact biomaterials, especially the cardiovascular devices. In this study, the regular titanium dioxide nanotube arrays were firstly prepared in situ on the titanium surface by anodic oxidation, followed by the immobilization of the complex of sodium alginate/carboxymethyl chitosan (SA/CS) on the self-assembled modified nanotube surface, the CO-releasing molecule (CORM-401) was finally grafted onto the surface to create a CO-releasing bioactive surface to enhance the biocompatibility. The results of scanning electron microscopy (SEM), X-ray energy dispersion spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS) revealed that the CO-releasing molecules were successfully immobilized on the surface. The modified nanotube arrays not only exhibited excellent hydrophilicity but also could slowly release CO gas molecules, and the amount of CO release increased when cysteine was added. Furthermore, the nanotube array can promote albumin adsorption while inhibit fibrinogen adsorption to some extent, demonstrating its selective albumin adsorption; although this effect was somewhat reduced by the introduction of CORM-401, it can be significantly enhanced by the catalytic release of CO. The results of hemocompatibility and endothelial cell growth behaviors showed that, as compared with the CORM-401 modified sample, although the SA/CS-modified sample had better biocompatibility, in the case of cysteine-catalyzed CO release, the released CO could not only reduce the platelet adhesion and activation as well as hemolysis rate, but also promote endothelial cell adhesion and proliferation as well as vascular endothelial growth factor (VEGF) and nitric oxide (NO) expression. As a result, the research of the present study demonstrated that the releasing CO from TiO2 nanotubes can simultaneously enhance the surface hemocompatibility and endothelialization, which could open a new route to enhance the biocompatibility of the blood-contacting materials and devices, such as the artificial heart valve and cardiovascular stents.

A nitric oxide-catalytically generating carboxymethyl chitosan/sodium alginate hydrogel coating mimicking endothelium function for improving the biocompatibility.

Thanks to their outstanding mechanical properties and corrosion resistance in physiological environments, titanium and its alloys are broadly explored in the field of intravascular devices. However, the biocompatibility is insufficient, causing thrombus formation and even implantation failure. In this study, inspired by the functions of endothelial glycocalyx and the NO-releasing of endothelial cells (ECs), a biomimetic coating (TNTA-Se) with three-dimensional gel-like structures and NO-catalytically generating ability was constructed on the titanium surface. To this end, the titanium alloy was firstly anodized and then annealed to form nanotube structures imitating the three-dimensional villous of glycocalyx, followed by the preparation of the Cu2+-loaded polydopamine intermediate layer for the immobilization of carboxymethyl chitosan and sodium alginate to form the hydrogel structure. Finally, an organoselenium compound (selenocystamine) as an active catalyst was covalently immobilized on the surface to develop a bioactive coating mimicking endothelial function with NO-generating activity. The surface morphologies and chemical structures of the biomimetic coating were characterized by scanning electron microscopy (SEM), energy dispersion X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), and the results indicated that the NO-catalytically generating hydrogel coating was successfully constructed. The results of water contact angle and protein adsorption suggested that the TNTA-Se coating exhibited excellent hydrophilicity, the promotion of bovine serum albumin (BSA) adsorption while the inhibition of fibrinogen (FIB) adsorption. Upon the addition of NO donor S-nitroso glutathione (GSNO) and reducing agent glutathione (GSH), the surface (TNTA-NO) displayed excellent blood compatibility and cytocompatibility to ECs. Compared with other surfaces, the TNTA-NO coating can not only further promote BSA adsorption and inhibit the adhesion and activation of platelets as well as hemolysis, but also significantly enhance ECs adhesion and proliferation and up-regulate VEGF and NO expression of ECs. The current study demonstrated that the NO-catalytically generating hydrogel coating on the titanium alloy can mimic the glycocalyx structure and endothelium function to catalyze a large number of NO donors in human blood to produce NO, and thus simultaneously enhance the surface hemocompatibility and endothelialization, representing a promising strategy for long-term cardiovascular implants of titanium-based devices.

Construction of Mussel-Inspired Dopamine-Zn2+ Coating on Titanium Oxide Nanotubes to Improve Hemocompatibility, Cytocompatibility, and Antibacterial Activity.

Zinc ions (Zn2+) are a highly potent bioactive factor with a broad spectrum of physiological functions. In situ continuous and controllable release of Zn2+ from the biomaterials can effectively improve the biocompatibility and antibacterial activity. In the present study, inspired by the adhesion and protein cross-linking in the mussel byssus, with the aim of improving the biocompatibility of titanium, a cost-effective one-step metal-catecholamine assembly strategy was developed to prepare a biomimetic dopamine-Zn2+ (DA-Zn2+) coating by immersing the titanium oxide nanotube (TNT) arrays on the titanium surface prepared by anodic oxidation into an aqueous solution containing dopamine (DA) and zinc ions (Zn2+). The DA-Zn2+ coatings with the different zinc contents exhibited excellent hydrophilicity. Due to the continuous release of zinc ions from the DA-Zn2+ coating, the coated titanium oxide nanotubes displayed excellent hemocompatibility characterized by platelet adhesion and activation and hemolysis assay. Moreover, the DA-Zn2+-coated samples exhibited an excellent ability to enhance endothelial cell (EC) adhesion and proliferation. In addition, the DA-Zn2+ coating can also enhance the antibacterial activity of the nanotubes. Therefore, long-term in situ Zn2+-releasing coating of the present study could serve as the bio-surfaces for long-term prevention of thrombosis, improvement of cytocompatibility to endothelial cells, and antibacterial activity. Due to the easy operation and strong binding ability of the polydopamine on various complicated shapes, the method of the present study can be further applied to other blood contact biomaterials or implantable medical devices to improve the biocompatibility.

Synthesis of Star 6-Arm Polyethylene Glycol-Heparin Copolymer to Construct Anticorrosive and Biocompatible Coating on Magnesium Alloy Surface.

Magnesium alloy has become a research hotspot of the degradable vascular stent materials due to its biodegradability and excellent mechanical properties. However, its rapid degradation rate after implantation and the limited biocompatibility restrict its application in clinic. Constructing a multifunctional bioactive polymer coating on the magnesium alloys represents one of the popular and effective approaches to simultaneously improve the corrosion resistance and biocompatibility. In the present study, the copolymer of 6-arm polyethylene glycol and heparin (PEG-Hep) was successfully synthesized and then immobilized on the surface of chitosan (Chi)-modified magnesium alloy surface through electrostatic interaction to improve the corrosion resistance and biocompatibility. The results of attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy showed that a dense and compact coating was created on the magnesium alloy surface. The coating displayed excellent hydrophilicity. At the same time, the as-prepared coating can significantly not only improve the corrosion potential, reduce the corrosion current and the pH changes of the immersion solution, but also keep a relatively intact surface morphology after immersing in simulated body fluid solution for 14 days, demonstrating that the coating can significantly improve the corrosion resistance of the magnesium alloy. Moreover, the magnesium alloy with PEG-Hep coating exhibited excellent hemocompatibility according to the results of the hemolysis rate and platelet adhesion and activation. In addition, the modified magnesium alloy had a good ability to promote the endothelial cell adhesion and proliferation. Therefore, the PEG-Hep multifunctional coating can be applied in the surface modification of the biodegradable magnesium alloy stent to simultaneously improve the corrosion resistance and biocompatibility.

One step preparation of multifunctional poly (ether sulfone) thin films with potential for wound dressing.

The increasing demand for higher-quality medical care has resulted in the obsolescence of traditional biomaterials. Medical care is currently transitioning from an era depending on single-functional biomaterials to one that is supported by multifunctional and stable biomaterials. Herein, long-lasting multifunctional poly(ether sulfone) thin films (MPFs) containing heparin-mimic groups and a quaternary ammonium compound (QAC) were prepared via semi-interpenetrating polymer network (SIPN) strategy. The MPFs, with rough surface and inner finger-like macrovoid, had better hydrophilicity and anti-protein fouling ability, as revealed by scanning electron microscopy (SEM), atomic force microscope (AFM) and water contact angle (WCA) and protein adsorption tests. The results of platelet adhesion and activation, and clotting time confirmed that the hemocompatibility of the MPFs was significantly improved. From cell culture and germ-culture test, it was noted that the overall trend of human umbilical vein endothelial cell (HUVEC) proliferation was enhanced by a combination of heparin-mimic groups and QAC, whereas the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was significantly prohibited. In addition, the MPFs were capable of modulating the expression level of basic fibroblast growth factor (bFGF) and transforming growth factor-beta1 (TGF-ß1) in fibroblast, which was beneficial to controlling the formation of hypertrophic scar. In summary, the MPFs had potential to be used in the field of wound management and the study might help guide the design of surface structure of wound dressing.

Preparation, release profiles and antibacterial properties of vancomycin-loaded Ca-P coating titanium alloy plate.

The aim of the study was to explore the feasibility of the Ca-P coating titanium alloy plate to be used as the vancomycin drug-delivery system by biomimetic coating technology. Through the X-ray diffraction study, the main components of the coatings were identified as octocalcium phosphate. The in vitro vancomycin release, bacteriostasis activity to Staphylococcus aureus (S. aureus), the scanning electron microscope (SEM) image and osteoblast adhesion and proliferation test of vancomycin-loaded Ca-P coating plate were evaluated. The bacteriostatic activity of the vancomycin-loaded Ca-P coating plate showed a continuous drug release and had an inhibitory effect on the growth of the S. aureus. In vitro osteoblast culture results showed that the Ca-P coating plate loaded with or without the vancomycin both obviously promoted the osteoblast attachment. It was suggested that the vancomycin-loaded Ca-P coating may be compounded in the surface of the internal fixators to reduce the incidence of the implant-associated infection.

Enhancing the antibacterial activity of biomimetic HA coatings by incorporation of norvancomycin.

BACKGROUND: Bacterial infections associated with the use of biomaterials remain a great challenge for orthopedic surgery. The main purpose of the work discussed in this paper was to improve the antibacterial activity of a biomimetic calcium phosphate (CP) coating widely used in orthopedic biomaterials by incorporation of norvancomycin in the biomimetic process. METHODS: CP coating and CP coating containing norvancomycin were produced on a titanium alloy (Ti6Al4V) surface by a biomimetic process. The morphology, surface crystal structure, and concentrations of elements in the coatings were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy-dispersive X-ray spectroscopy (EDX), respectively. The amount of norvancomycin and its release were investigated by UV-visible spectroscopy. MTT was used to investigate cell behavior. The morphology of adhered bacteria was observed by SEM. Antibacterial activity was expressed as inhibition zone by using Staphylococcus aureus (ATCC 25923) as model bacteria. RESULTS: Results from SEM, EDX, and XRD revealed formation of a hydroxyapatite (HA) coating. The amount of antibiotic in the CP coating increased with increasing concentration of norvancomycin in the coating solution, followed by a plateau when the concentration of norvancomycin in the coating solution reached 600 mg/l. Approximately 2.16 µg norvancomycin per mg coating was co-precipitated with the CP layer onto titanium alloy discs when 600 mg/l norvancomycin coating solution was applied. The norvancomycin had a fast release profile followed by slow release. The MTT test of osteoblast cell cultures suggested that coatings containing norvancomycin did not cause any cytotoxicity compared with the CP coating and control titanium plate. The antibacterial activity test showed that the norvancomycin released from the coatings inhibited the growth of Staphylococcus aureus; more bacteria were found on the CP coating than on the norvancomycin-loaded coating. CONCLUSIONS: A norvancomycin-loaded HA-like coating was successfully obtained on titanium surfaces. The norvancomycin incorporated had no negative effects on osteoblast cell behavior. The released norvancomycin results in excellent antibacterial activity of Ca-P coatings. Therefore, incorporation of norvancomycin can enhance antibacterial activity and the norvancomycin-loaded CP coating can be used to inhibit post-surgical infections in orthopaedics.

Immobilization of bioactive complex on the surface of magnesium alloy stent material to simultaneously improve anticorrosion, hemocompatibility and antibacterial activities.

Magnesium alloy represents one of the most potential biodegradable vascular stent materials due to its good biodegradability, biocompatibility and suitable mechanical properties, whereas the rapid degradation in physiological environment and the limited biocompatibility remain the challenges. In this study, graphene oxide (GO) was firstly functionalized by chitosan (GOCS), followed by loading zinc ions and propranolol to obtain GOCS@Zn/Pro complex, which was finally covalently immobilized on the self-assembled modified magnesium alloy surface to enhance the corrosion resistance and biocompatibility. The multi-functional coating can significantly improve the corrosion resistance and reduce the degradation rate of the magnesium alloy. Furthermore, the coating can significantly inhibit platelet adhesion and activation, reduce hemolysis rate, prolong activated partial thromboplastin time (APTT), and thus improve the blood compatibility of the magnesium alloy. In addition, the modified magnesium alloy can not only significantly promote the endothelial cell adhesion and proliferation, up-regulate the expression of vascular endothelial growth factor (VEGF) and nitric oxide (NO), but also endow the materials with good antibacterial properties. Therefore, the method of the present study can be used to modify magnesium alloy stent materials to simultaneously enhance corrosion resistance and blood compatibility, promote endothelialilization, and inhibit infections.

Tumor Cell Distinguishable Nanomedicine Integrating Chemotherapeutic Sensitization and Protection.

Theoretically, with a high enough drug dosage, cancer cells could be eliminated. However, the dosages that can be administered are limited by the therapeutic efficacy and side effects of the given drug. Herein, a nanomedicine integrating chemotherapeutic sensitization and protection was developed to relieve the limitation of administration dosage and to improve the efficacy of chemotherapy. The nanomedicine was endowed with the function of synergistically controlled release of CO and drugs under near-infrared (NIR) light irradiation. CO photo-induced release system (COPIRS) was synthesized by constructing an electron excitation-electron transfer group-electron-induced CO release structure and was used as the hydrophobic part, and then hydrophilic polymer (polyethylene glycol; PEG) was introduced by a thermal-responsive groups (DA group), forming a near-infrared-induced burst-release nanocarrier. In vitro and in vivo experiments showed that the nanomedicine can distinguish between tumor and normal cells and regulates the resistance of these different cells through the controlled release of carbonic oxide (CO), simultaneously enhancing the efficacy of chemotherapy drugs on tumor cells and chemotherapeutic protection on normal cells. This strategy could solve the current limitations on dosages due to toxicity and provide a solution for tumor cure by chemotherapy.

A Rapid Dual-Responsive Releasing Nano-Carrier by Decomposing the Copolymer and Reversing the Core Dissolution.

The accumulation of nanotechnology-based drugs has been realized in various ways. However, the concentration of drugs encapsulated by nanomaterials is not equal to the concentration of effective drugs; often, the drugs become effective only when they are released from the nanomaterials as free drugs. This means only when the drugs are rapidly released after the accumulated drug-encapsulating nanomaterials can they truly achieve the purpose of increasing the concentration of drugs in the tumor. Therefore, we herein report a dual-response nano-carrier of glutathione and acid to achieve the rapid release of encapsulated drug and increase the effective drug concentration in the tumor. The nano-carrier was constructed using a dual-responsive amphiphilic copolymer, composed of polyethylene glycol and hydrophobic acetylated dextran and connected by a disulfide bond. In the tumor microenvironment, disulfide bonds could be biodegraded by glutathione that is overexpressed in the tumor, exposing the core of nano-carrier composed of acetylated dextran. Then the acidic environment would induce the deacetylation of acetylated dextran into water-soluble dextran. In this way, the nano-carrier will degrade quickly, realizing the purpose of rapid drug release. The results showed that the drug release rate of dual-responsive nano-carrier was much higher than that of glutathione or acid-responsive nano-carrier alone. Furthermore, both in vitro and in vivo experiments confirmed that dual-responsive nano-carrier possessed more efficient anti-tumor effects. Therefore, we believe that dual-responsive nano-carriers have better clinical application prospects.

Progress on Precise Regulation of Vascular Intimal Repair by a Surface Coating of Vascular Stent.

In the past few decades, drug-eluting stents have made significant contributions to the treatment of coronary heart disease. However, due to the delayed healing of endothelial injuries caused by antiproliferative drugs and insufficient biocompatibility of vascular stent materials, late in-stent thrombosis and restenosis remain major challenges. Surface modification of cardiovascular materials to construct a biological functional layer that can regulate the behavior of blood and vascular cells is an effective way to improve the clinical performance of vascular stents. This paper reviewed the common methods of surface bio-functional modification of cardiovascular materials and especially proposed that take advantage of the new concept of precision medicine, as well as the precise and orderly regulation properties of cardiovascular disease-related gene fragments on vascular biological response behavior, the construction of gene-eluting stents which can in-situ regulate vascular intimal repair at the molecular and genetic level will become an important research direction in the future.

Loading Gentamicin and Zn2+ on TiO2 Nanotubes to Improve Anticoagulation, Endothelial Cell Growth, and Antibacterial Activities.

Titanium and its alloys are widely used in blood-contacting implantable and interventional medical devices; however, their biocompatibility is still facing great challenges. In the present study, in order to improve the biocompatibility and antibacterial activities of titanium, TiO2 nanotubes were firstly in situ prepared on the titanium surface by anodization, followed by the introduction of polyacrylic acid (PAA) and gentamicin (GS) on the nanotube surface by layer-by-layer assembly, and finally, zinc ions were loaded on the surface to further improve the bioactivities. The nanotubes displayed excellent hydrophilicity and special nanotube-like structure, which can selectively promote the albumin adsorption, enhance the blood compatibility, and promote the growth of endothelial cells to some degree. After the introduction of PAA and GS, although the superhydrophilicity cannot be achieved, the results of platelet adhesion, cyclic guanosine monophosphate (cGMP) activity, hemolysis rate, and activated partial thromboplastin time (APTT) showed that the blood compatibility was improved, and the blood compatibility was further enhanced after zinc ion loading. On the other hand, the modified surface showed good cytocompatibility to endothelial cells. The introduction of PAA and zinc ions not only promoted the adhesion and proliferation of endothelial cells but also upregulated expression of vascular endothelial growth factor (VEGF) and nitric oxide (NO). The slow and continuous release of GS and Zn2+ over 14 days can significantly improve the antibacterial properties. Therefore, the present study provides an effective method for the surface modification of titanium-based blood-contacting materials to simultaneously endow with good blood compatibility, endothelial growth behaviors, and antibacterial properties.

The Janus-SAM approach for the flexible functionalization of gold and titanium oxide surfaces.

A novel approach is developed to address the requirement of multiple stamps and inks for microcontact printing (microCP) onto different substrate surfaces. This approach relies on microCP one divalent molecule, which is able to form Janus self-assembled monolayers (JSAMs) with a labile cleavable centre, thus providing a facile method for the chemical derivatization of different substrate surfaces. This study presents an answer to the challenges presented within a highly versatile application, microCP. N-(3-diethylphosphatoxy)propyl-11-mercaptoundecanamide is used for the first time as an ink for microCP onto both gold and titanium oxide surfaces, utilizing the same polydimethylsiloxane stamp. Following printing, the JSAMs are enzymatically treated on these two different substrates to reveal different functional groups. The newly formed surfaces are subjected to additional surface reactions and used for the chemisorption of bovine serum albumin. At each stage, these JSAMs are characterized by X-ray photoelectron spectroscopy and dynamic water-contact-angle measurements. Confocal laser scanning microscopy is used for the characterization of the adsorbed proteins.

Molecular Antenna-Sensitized Upconversion Nanoparticle for Temperature Monitored Precision Photothermal Therapy.

BACKGROUND: Photothermal therapy with accurate and real-time temperature detection is desired in clinic. Upconversion nanocrystals (UCNs) are candidate materials for simultaneous temperature detection and photothermal agents carrying. However, the weak luminescence and multiple laser excitations of UCNs limit their application in thermal therapy. MATERIALS AND METHODS: NaYF4:Yb3+,Er3+,Nd3+, PL-PEG-NH2, IR-806 and folic acid are selected as structural components. A nanoprobe (NP) integrated with efficient photothermal conversion and sensitive temperature detection capabilities is synthesized for precise photothermal therapy. The probes are based on near-infrared upconversion nanocrystals doped with Yb, Er and Nd ions, which can be excited by 808 nm light. IR-806 dye molecules are modified on the surface as molecular antennas to strongly absorb near-infrared photons for energy transfer and conversion. RESULTS: The results show that under an 808 nm laser irradiation upconversion luminescence of the nanocrystals is enhanced based on both the Nd ion absorption and the FRET energy transfer of IR-806. The luminescence ratio at 520 and 545 nm is calculated to accurately monitor the temperature of the nanoparticles. The temperature of the nanoprobes increases significantly through energy conversion of the molecular antennas. The nanoparticles are found successfully distributed to tumor cells and tumor tissue due to the modification of the biocompatible molecules on the surface. Tumor cells can be killed efficiently based on the photothermal effect of the NPs. Under the laser irradiation, temperature at mouse tumor site increases significantly, tissue necrosis and tumor cell death can be observed. CONCLUSION: Precision photothermal therapy can thus be achieved by highly efficient near-infrared light absorption and accurate temperature monitoring, making it promising for tumor treatment, as well as the biological microzone temperature detection.

Layer-by-layer deposition of bioactive layers on magnesium alloy stent materials to improve corrosion resistance and biocompatibility.

Magnesium alloy is considered as one of the ideal cardiovascular stent materials owing to its good mechanical properties and biodegradability. However, the in vivo rapid degradation rate and the insufficient biocompatibility restrict its clinical applications. In this study, the magnesium alloy (AZ31B) was modified by combining the surface chemical treatment and in-situ self-assembly of 16-phosphonyl-hexadecanoic acid, followed by the immobilization of chitosan-functionalized graphene oxide (GOCS). Heparin (Hep) and GOCS were alternatively immobilized on the GOCS-modified surface through layer by layer (LBL) to construct the GOCS/Hep bioactive multilayer coating, and the corrosion resistance and biocompatibility were extensively explored. The results showed that the GOCS/Hep bioactive multilayer coating can endow magnesium alloys with an excellent in vitro corrosion resistance. The GOCS/Hep multilayer coating can significantly reduce the hemolysis rate and the platelet adhesion and activation, resulting in an excellent blood compatibility. In addition, the multilayer coating can not only enhance the adhesion and proliferation of the endothelial cells, but also promote the vascular endothelial growth factor (VEGF) and nitric oxide (NO) expression of the attached endothelial cells on the surfaces. Therefore, the method of the present study can be used to simultaneously control the corrosion resistance and improve the biocompatibility of the magnesium alloys, which is expected to promote the application of magnesium alloys in biomaterials or medical devices, especially cardiovascular stent.

Improved Blood Compatibility and Endothelialization of Titanium Oxide Nanotube Arrays on Titanium Surface by Zinc Doping.

Titanium dioxide nanotube arrays are widely used in biomaterials due to their unique tubular structure and tunable biocompatibility. In the present study, titanium oxide nanotube arrays with different diameters were prepared on the titanium surface by anodization, followed by zinc doping using hydrothermal treatment to enhance the biocompatibility. Both the nanotube dimensions and zinc doping had obvious influences on the hydrophilicity, protein adsorption, blood compatibility, and endothelial cell behaviors of the titanium surface. The increase of the diameter and zinc doping can improve the hydrophilicity of the titanium surface. The increase of nanotube diameter could reduce the albumin adsorption while increasing the fibrinogen adsorption. However, zinc doping can simultaneously promote the adsorption of albumin and fibrinogen, and the effect was more obvious for albumin. Zinc doping can significantly improve the blood compatibility of the titanium oxide nanotubes because it cannot only increase the activity of cyclophosphate guanylate (cGMP) but also significantly reduce the platelets adhesion and hemolysis rate. Moreover, it was also found that both the smaller diameter and zinc doping nanotubes can enhance the endothelial cell adhesion and proliferation as well as up-regulate the expression of NO and VEGF. Therefore, the zinc doped titanium dioxide nanotube array can be used to simultaneously improve the blood compatibility and promote endothelialization of the titanium-based biomaterials and implants, such as intravascular stents.

Effects of diameters and crystals of titanium dioxide nanotube arrays on blood compatibility and endothelial cell behaviors.

Titanium dioxide nanotube arrays (TNTAs) have attracted extensive attention in the fields of biomaterials and biomedicine due to their unique tubular structure and good biocompatibility. In this paper, TNTAs with different nanotube diameters and lengths were in situ prepared on the titanium surface by the anodic oxidation, and their crystal structures were further changed by annealing treatment. The effects of TNTAs with different diameters and crystals on the blood compatibility and endothelial cell behaviors were investigated. The results showed that TNTAs with the diameter of 30∼90 nm can be obtained by controlling the anodization voltage, and annealing treatment did not obviously change the diameters and lengths of the nanotube arrays. However, annealing treatment can transform the amorphous TNTAs into the anatase structure. The diameter and crystal structure of the nanotube arrays played a key role in the surface wettability and protein adsorption. The nanotube array with larger diameter displayed better surface hydrophilicity as compared to the pristine titanium, and annealing treatment further enhanced the hydrophilicity. As compared to the pristine titanium, the nanotube array structure had the characteristic of selective protein adsorption, and the nanotube array can promote the bovine serum albumin (BSA) adsorption and prevent the fibrinogen (FIB) adsorption, however, the increase of nanotube diameter could reduce BSA adsorption and increase FIB adsorption. Besides, the nanotube array with anatase structure can promote BSA adsorption while reduce FIB adsorption. Therefore, the TNTAs with smaller diameter and anatase crystal had good blood compatibility and cell compatibility, they can not only reduce platelet adhesion and hemolysis rate but also increase endothelial cell adhesion and proliferation. In conclusion, the nanotube arrays of the present study can be used to improve the cell compatibility and blood compatibility of the titanium implants.