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.

Anticoagulation and endothelial cell behaviors of heparin-loaded graphene oxide coating on titanium surface.

Owing to its unique physical and chemical properties, graphene oxide (GO) has attracted tremendous interest in many fields including biomaterials and biomedicine. The purpose of the present study is to investigate the endothelial cell behaviors and anticoagulation of heparin-loaded GO coating on the titanium surface. To this end, the titanium surface was firstly covered by the polydopamine coating followed by the deposition of the GO coating. Heparin was finally loaded on the GO coating to improve the blood compatibility. The results of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) indicated that the heparin-loaded GO coating was successfully created on the titanium surface. The scanning electron microscopy (SEM) images indicated that a relative uniform GO coating consisting of multilayer GO sheets was formed on the substrate. The hydrophilicity of the titanium surface was enhanced after the deposition of GO and further improved significantly by the loading heparin. The GO coating can enhance the endothelial cell adhesion and proliferation as compared with polydopamine coating and the blank titanium. Loading heparin on the GO coating can significantly reduce the platelet adhesion and prolong the activated partial thromboplastin time (APTT) while not influence the endothelial cell adhesion and proliferation. Therefore, the heparin-loaded GO coating can simultaneously enhance the cytocompatibility to endothelial cells and blood compatibility of biomaterials. Because the polydopamine coating can be easily prepared on most of biomaterials including polymer, ceramics and metal, thus the approach of the present study may open up a new window of promising an effective and efficient way to promote endothelialization and improve the blood compatibility of blood-contact biomedical devices such as intravascular stents.

Effects of self-assembly of 3-phosphonopropionic acid, 3-aminopropyltrimethoxysilane and dopamine on the corrosion behaviors and biocompatibility of a magnesium alloy.

Magnesium based alloys are attracting tremendous interests as the novel biodegradable metallic biomaterials. However, the rapid in vivo degradation and the limited surface biocompatibility restrict their clinical applications. Surface modification represents one of the important approaches to control the corrosion rate of Mg based alloys and to enhance the biocompatibility. In the present study, in order to improve the corrosion resistance and surface biocompatibility, magnesium alloy (AZ31B) was modified by the alkali heating treatment followed by the self-assembly of 3-phosphonopropionic acid, 3-aminopropyltrimethoxysilane (APTMS) and dopamine, respectively. The results of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectra (XPS) indicated that the molecules were successfully immobilized on the magnesium alloy surface by the self-assembly. An excellent hydrophilic surface was obtained after the alkali heating treatment and the water contact angle increased to some degree after the self-assembly of dopamine, APTMS and 3-phosphonopropionic acid, however, the hydrophilicity of the modified samples was better than that of the pristine magnesium substrate. Due to the formation of the passivation layer after the alkali heating treatment, the corrosion resistance of the magnesium alloy was obviously improved. The corrosion rate further decreased to varying degrees after the self-assembly surface modification. The blood compatibility of the pristine magnesium was significantly improved after the surface modification. The hemolysis rate was reduced from 56% of the blank magnesium alloy to 18% of the alkali heating treated sample and the values were further reduced to about 10% of dopamine-modified sample and 7% of APTMS-modified sample. The hemolysis rate was below 5% for the 3-phosphonopropionic acid modified sample. As compared to the pristine magnesium alloy, fewer platelets were attached and activated on the modified surfaces and the activated partial thromboplastin times (APTT) were prolonged to some degree. Furthermore, the modified samples showed good cytocompatibility. Endothelial cells exhibited the improved proliferative profiles in terms of CCK-8 assay as compared to those on the pristine magnesium alloy. The modified samples showed better endothelial cell adhesion and spreading than the pristine magnesium alloy. Taking all these results into consideration, the method of this study can be used to modify the magnesium alloy surface to improve the corrosion resistance and biocompatibility simultaneously.

Fabrication of anticoagulation layer on titanium surface by sequential immobilization of poly (ethylene glycol) and albumin.

This paper presents a simple method to sequentially immobilize poly (ethylene glycol) (PEG) and albumin on titanium surface to enhance the blood compatibility. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) analysis indicated that PEG and albumin were successfully immobilized on the titanium surface. Water contact angle results showed a better hydrophilic surface after the immobilization. The immobilized PEG or albumin can not only obviously prevent platelet adhesion and activation but also prolong activated partial thromboplastin time (APTT), leading to the improved anticoagulation. Moreover, immobilization of albumin on PEG-modified surface can further improve the anticoagulation. The approach in the present study provides an effective and efficient method to improve the anticoagulation of blood-contact biomedical devices such as coronary stents.

Improved anticoagulation of titanium by sequential immobilization of oligo(ethylene glycol) and 2-methacryloyloxyethyl phosphorylcholine.

Titanium and its alloys have been widely used for blood-contacting biomedical devices; however, their blood compatibility needs to be improved. In this study, titanium surface was modified by sequential immobilization of oligo(ethylene glycol) (OEG) and 2-methacryloyloxyethyl phosphorylcholine (MPC) to improve its anticoagulation. Water contact angle results showed an excellent hydrophilic surface after the immobilization. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) confirmed that OEG and MPC were successfully immobilized on titanium surface. Static platelet adhesion and APTT (activated partial thromboplastin time) experiments suggested that the anticoagulation of titanium was significantly enhanced by the immobilization of OEG and further by subsequent MPC grafting. The approach in the present study opens up a window of promising an effective and efficient method to improve the anticoagulation of blood-contact biomedical devices such as coronary stents.

Control of osteoblast cells adhesion and spreading by microcontact printing of extracellular matrix protein patterns.

In this study, we report a simple method for creating extracellular matrix (ECM) protein patterns to control osteoblast cell adhesion and spreading. The fibronectin patterns are directly produced on polystyrene (PS) surfaces by microcontact printing (µCP). Confocal laser scanning microscopy (CLSM) images show that protein patterns are successfully fabricated on PS surfaces. Newborn rat osteoblast cells are then seeded on these protein patterns and cultured for 4 days. The results demonstrate that osteoblast cells preferentially adhere and grow on the protein areas. The pattern dimensions have significant influences on cell behaviors, including cell adhesion, spreading, distribution, and growth direction. Therefore, it is possible to control the cell morphology and even cell function by carefully designing the pattern shapes and sizes. The present study suggests that the ECM protein patterns can be used to modify biomaterials' surfaces and spatially control the morphologies of osteoblast cells. We believe that our work could find applications for creating patterned bioactive surfaces to control cell adhesion, spreading and cell function. It may be helpful for the development of novel implantable biomaterials, such as artificial bone implants, where control of interfacial biological interactions between implants and cells would be preferable.

Preparation, characterization and in vitro anticoagulation of emodin-eluting controlled biodegradable stent coatings.

In this study, emodin-eluting poly(lactide-co-glycolide) (PLGA) coating stents and emodin-loaded PLGA films were prepared to explore the potential application of emodin-eluting stent for treating cardiovascular disease. Fourier transform infrared spectra (FTIR) showed all characteristic adsorption peaks of emodin in emodin-loaded PLGA film in comparison to pure emodin. The balloon expansion experiment and surface morphology observation suggested that the integrated emodin-eluting coatings were successfully obtained on the stainless steel surfaces and the coatings had the ability to withstand the strains imparted during balloon experiment. The drug release profile revealed the nearly linear release curve without obvious burst release for different doses of emodin-eluting stents. As compared with stainless steel and PLGA, in vitro platelet adhesion and APTT (activated partial thromboplastin time) tests revealed better blood compatibility of emodin-eluting stent. In conclusion, the results of the present study showed that the emodin-eluting stent has a potential application for treating cardiovascular disease.

Efficacy of a norvancomycin-loaded, PDLLA-coated plate in preventing early infection of rabbit tibia fracture.

Despite improvements in surgical techniques and implant designs in orthopedic surgery, implantation-associated infections are still a challenging problem for surgeons. The goal of this study was to evaluate the efficacy of a norvancomycin-loaded, PDLLA-coated stainless steel plate vs an uncoated stainless steel plate in a rabbit model (n=50). The norvancomycin was delivered from a biodegradable poly(D,L-lactide) (PDLLA) coating of a stainless steel plate. Intraoperatively, rabbit tibia fractures were contaminated with Staphylococcus aureus (10(5) colony forming units) after plate implantation. The implants were either uncoated or coated with PDLLA and norvancomycin. In vivo drug release profiles showed that the norvancomycin release rate was decreased by increasing the time. The norvancomycin concentration in the tissue around the plate was higher than the minimum inhibitory concentration on the 14th day after implantation surgery. The animals were followed up for 28 days. Radiographic examinations were performed, and C-reactive protein and erythrocyte sedimentation rate were determined. Infection was evaluated by histological, microbiological, and radiological analysis. Eight of 25 rabbits (32%) implanted with the norvancomycin-loaded, PDLLA-coated plates were infected. Twenty-three of 25 rabbits (92%) implanted with the uncoated plates were infected (P<.05). The norvancomycin-loaded, PDLLA-coated plate may be used to treat open fractures to reduce the incidence of early infection.

Preparation and in vitro release profiles of drug-eluting controlled biodegradable polymer coating stents.

In the present study, the different drug-eluting controlled biodegradable polymer coatings were fabricated on stainless steel stents. The coatings were not only uniform and smooth but also had excellent mechanical property. The drug release profiles of drug-eluting stents were studied in detail in this study. Depending on the drug type, different drug-eluting stents exhibited different drug release profile. There were two basic release profiles for different drug-eluting stents, i.e., two-phase release profile with burst release or linear release profile without burst release. Incorporating heparin in the rapamycin or curcumin eluting stents can improve the average drug release rate of both and the burst release of rapamycin. The average drug release rate increased with the increase of drug loading but was not proportional to increase of the ratio of drug/polymer. Fabricating the control release layer on rapamycin-eluting stent surface can prevent the burst release of rapamycin and prolong the release period of rapamycin. All results showed that the drug release profile of drug-eluting stents depends on many parameters including drug type, ratio of drug/polymer, and drug carrier properties.