Piranha solution treatment: A facile method for improving the antithrombotic ability and regulating smooth muscle cell growth on blood contact materials.

Blood contact materials require strong anti-fouling capabilities to avoid thrombus formation. Recently, TiO2-based photocatalytic antithrombotic treatment has gained focus. Nevertheless, this method is restricted to titanium materials with photocatalytic abilities. This study offers an alternative solution that can be applied to a broader range of materials: piranha solution treatment. Our findings revealed that the free radicals generated by the treatment effectively altered the surface physicochemical properties of various inorganic materials, enhancing their surface hydrophilicity and oxidizing organic contaminants, thus improving their antithrombotic properties. Additionally, the treatment resulted in contrasting effects on the cellular affinity of SS and TiO2. While it significantly reduced the adhesion and proliferation of SMCs on SS surfaces, it significantly enhanced these on TiO2 surfaces. These observations suggested that the impact of the piranha solution treatment on the cellular affinity of biomaterials was closely tied to the intrinsic properties of the materials. Thus, materials suitable for piranha solution treatment could be selected based on the functional requirements of implantable medical devices. In conclusion, the broad applicability of piranha solution surface modification technology in both blood-contact and bone implant materials highlights its promising prospects.

Photofunctionalized TiO2-TiN micropattern coating with anticoagulant properties and ECs contact-guidance effect.

Titanium nitride (TiN) and titanium dioxide (TiO2) are two titanium-based coatings commonly used in cardiovascular stent surface engineering. Generally, TiN has good mechanical properties and endothelial cell (ECs) compatibility but poor anticoagulant properties and cannot modulate cell growth orientation and morphology. TiO2 has excellent corrosion resistance and biosafety. Besides, TiO2 has the photocatalytic anticoagulant property, which can migrate to other materials tens of microns away. Based on the above properties, a striped TiO2-TiN micropattern coating was designed and fabricated in this study, and the coating was photofunctionalized by UV irradiation. The obtained photo-functionalized TiO2-TiN micropattern coating showed anticoagulant properties by the migrating effect of the photocatalytic anticoagulant property of TiO2. Besides, the TiO2-TiN micropattern coatings showed ECs compatibility. Furthermore, the growth orientation and cell shape of ECs on TiO2-TiN samples were effectively regulated by the stripe pattern's contact guidance effect, which was particularly evident on the photo-functionalized TiO2-TiN samples. We envision that this photofunctionalized TiO2-TiN striped micropattern coating has significant potential for the surface engineering of vascular stents.

Multi-functional plant flavonoids regulate pathological microenvironments for vascular stent surface engineering.

In-stent restenosis (ISR) and late thrombosis, usually caused by excessive smooth muscle cell (SMC) proliferation and delayed endothelial layer repair, respectively, are the main risks for the failure of vascular stent implantation. For years, modification of stents with biomolecules that could selectively inhibit SMC proliferation and support endothelial cell (EC) growth had drawn extensive attention. However, the modulatory effect of these biomolecules faces the impact of oxidative stress, inflammation, and hyperlipidemia of the pathological vascular microenvironment, which is caused by the stent implantation injury and atherosclerosis lesions. Here, we modified stents with a natural and multi-functional flavonoid, baicalin (BCL), using poly-dopamine (PDA) coating technology to combat the harmful impact of the pathological microenvironment. Stent with an appropriate BCL immobilization density (approximately 2.03 µg/cm2) successfully supported ECs growth while inhibited SMC proliferation. Furthermore, baicalin-modified surfaces regulated the oxidative stress, inflammation, and high-lipid of the pathological microenvironment to inhibit endothelial dysfunction and the oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cells formation. In vivo results showed that baicalin-modified stents exhibited significant anti-ISR, anti-inflammatory, and endothelialization-promoting functions. Our study suggests that the multi-functional baicalin with pathological microenvironment-regulation (PMR) effect has potential use in the surface engineering of cardiovascular devices. STATEMENT OF SIGNIFICANCE: Empowering vascular stents with selective modulation of smooth muscle cells and endothelial cells by surface technology has become an important research direction for stent surface engineering. However, stent coatings that can furthermodulate the pathological microenvironment of blood vessels have been rarely reported. In this study, we constructed a multifunctional coating based on a flavonoid, baicalin, which can selectively modulate vascular wall cells and improve the pathological microenvironment. This study may provide a reference for developing advanced vascular stents.

Enhanced Hemocompatibility of Silver Nanoparticles Using the Photocatalytic Properties of Titanium Dioxide.

Silver nanoparticles (AgNPs) are widely used because of their excellent antimicrobial properties. However, the poor hemocompatibility limits the application of AgNPs in blood contact materials. General approaches to improve the hemocompatibility of AgNPs-containing surfaces are to construct barrier layers or co-immobilize anticoagulant biomolecules. But such modification strategies are often cumbersome to prepare and have limited applications. Therefore, this study proposes a simple UV-photo-functionalization strategy to improve the hemocompatibility of AgNPs. We loaded AgNPs onto titanium dioxide (TiO2) nanoparticles to form a composite nanoparticles (Ag@TiO2NPs). Then, UV treatment was performed to the Ag@TiO2NPs, utilizing the diffusible photo-induced anticoagulant properties of TiO2 nanoparticles to enhance the hemocompatibility of AgNPs. After being deposited onto the PU surface, the photo-functionalized Ag@TiO2NPs coating showed excellent antibacterial properties against both Gram-positive/Gram-negative bacteria. Besides, In vitro and ex-vivo experiments demonstrated that the photo-functionalized Ag@TiO2NPs coating had desirable hemocompatibility. This modification strategy can provide a new solution idea to improve the hemocompatibility of metal nanoparticles.

Multifunctional Baicalin-Modified Contact Lens for Preventing Infection, Regulating the Ocular Surface Microenvironment and Promoting Corneal Repair.

Corneal injury inevitably leads to disruption of the ocular surface microenvironment, which is closely associated with delayed epithelial cell repair and the development of infection. Recently, drug-loaded therapeutic contact lenses have emerged as a new approach to treating corneal injury due to their advantages of relieving pain, promoting corneal repair, and preventing infection. However, few therapeutic contact lenses could modulate the ocular surface's inflammation and oxidative stress microenvironment. To address this, in this study, we covalently immobilized multifunctional baicalin (BCL), a flavon molecular with anti-inflammatory, anti-oxidative stress, and antibacterial capabilities, onto the surface of the contact lens. The BCL-modified contact lens showed excellent optical properties, powerful antibacterial properties, and non-toxicity to endothelial cells. Furthermore, the BCL-modified contact lens could significantly modulate the ocular surface microenvironment, including inhibition of macrophage aggregation and resistance to epithelium damage caused by oxidative stress. In animal models, BCL-modified corneal contact lens effectively promoted corneal epithelial cells repair. These excellent properties suggested that multifunctional BCL molecules had great application potential in the surface engineering of ophthalmic medical materials.

Cell-friendly photo-functionalized TiO2 nano-micro-honeycombs for selectively preventing bacteria and platelet adhesion.

Titanium dioxide (TiO2) is a widely used biomaterial. It is a great challenge to confer antibacterial and antithrombotic properties to TiO2 while maintaining its cell affinity. Here, we developed a new strategy to achieve the above goal by comprehensively controlling the chemical cues and geometrical cues of the surface of TiO2. Using colloidal etching technology and UV irradiation treatment, we obtained the photofunctionalized nano-micro-honeycomb structured TiO2. The honeycomb structured increased the photocatalytic activity of TiO2, which endowed TiO2 with photo-induced superhydrophilicity to inhibit bacterial adhesion. The high photocatalytic activity also induced the strong photocatalytic oxidation of TiO2 surface organic adsorbates to suppress fibrinogen and platelet attachment. In addition, owing to the micropore trapping-isolation effect on the bacteria and the nano-frames' contact guidance effect on the growth and spreading of platelet pseudopods, the honeycomb structure also shows a considerable inhibiting effect on bacterial and platelet adhesion. Therefore, due to the controlled chemical and geometrical cues' synergistic effect, the photo-functionalized TiO2 honeycomb structure shows excellent bacterial-adhesion resistance and antithrombotic properties. More importantly, the photo-functionalized TiO2 honeycomb did not inhibit the adhesion and growth of endothelial cells (ECs) after culturing for 3 d, indicating a good cell affinity that the traditional antifouling surfaces do not possess.

Photo-functionalized TiO2 nanotubes decorated with multifunctional Ag nanoparticles for enhanced vascular biocompatibility.

Titanium dioxide (TiO2) has a long history of application in blood contact materials, but it often suffers from insufficient anticoagulant properties. Recently, we have revealed the photocatalytic effect of TiO2 also induces anticoagulant properties. However, for long-term vascular implant devices such as vascular stents, besides anticoagulation, also anti-inflammatory, anti-hyperplastic properties, and the ability to support endothelial repair, are desired. To meet these requirements, here, we immobilized silver nanoparticles (AgNPs) on the surface of TiO2 nanotubes (TiO2-NTs) to obtain a composite material with enhanced photo-induced anticoagulant property and improvement of the other requested properties. The photo-functionalized TiO2-NTs showed protein-fouling resistance, causing the anticoagulant property and the ability to suppress cell adhesion. The immobilized AgNPs increased the photocatalytic activity of TiO2-NTs to enhances its photo-induced anticoagulant property. The AgNP density was optimized to endow the TiO2-NTs with anti-inflammatory property, a strong inhibitory effect on smooth muscle cells (SMCs), and low toxicity to endothelial cells (ECs). The in vivo test indicated that the photofunctionalized composite material achieved outstanding biocompatibility in vasculature via the synergy of photo-functionalized TiO2-NTs and the multifunctional AgNPs, and therefore has enormous potential in the field of cardiovascular implant devices. Our research could be a useful reference for further designing of multifunctional TiO2 materials with high vascular biocompatibility.

Photofunctionalized and Drug-Loaded TiO2 Nanotubes with Improved Vascular Biocompatibility as a Potential Material for Polymer-Free Drug-Eluting Stents.

Implantation of a drug-eluting stent is the most common treatment method for patients with cardiovascular atherosclerosis. However, this treatment may delay re-endothelialization, and the drug polymer-coated stent may induce thrombosis months after a stent implantation. The development of polymer-free drug-eluting stents is a promising approach to overcome these shortcomings. Titanium dioxide nanotubes (TiO2-NTs) are excellent drug carriers and have been considered as a potential material for polymer-free drug-eluting stents. However, TiO2-NTs reportedly induce severe blood clotting, which is a significant shortcoming for use as a stent. Vascular stents must be compatible with blood and must have antibacterial, anti-inflammatory, and selective inhibitory activities in the abnormal hyperplasia of smooth muscle cells, instead of delaying the re-endothelialization of endothelial cells. To meet these requirements, we presented a composite material that featured ultraviolet (UV) irradiation of TiO2-NTs-containing silver nanoparticles (AgNPs). The AgNPs were loaded in the lumen of TiO2-NTs as a representative compound to suppress the inflammatory response and hyperplasia. UV irradiation was performed as a novel method to improve the anticoagulant ability of the AgNP-loaded TiO2-NTs. The chemical state and biocompatibility of the UV-TiO2-NTs@AgNPs were evaluated. UV irradiation strongly improved the anticoagulant ability of the TiO2-NTs and moderated the release of Ag+ from AgNPs, which selectively suppressed the inflammatory response and hyperplasia. Furthermore, the UV-TiO2-NTs@AgNPs-2 displayed enhanced biocompatibility evidenced by the inhibition of platelet adhesion, bactericidal activity, selective suppression of the smooth muscle cell proliferation, and inhibition of the adhesion of macrophages. The collective findings indicate the potential of the photofunctionalized TiO2-NTs loaded with AgNPs as a material for polymer-free drug-eluting stents.

Hyaluronic Acid Nanoparticle Composite Films Confer Favorable Time-Dependent Biofunctions for Vascular Wound Healing.

Vascular stent implantation is the primary treatment for coronary artery disease. Surface modification of coronary stents is a topic of interest to prevent thrombosis and restenosis and to promote endothelization. However, bioactive coatings on implants have not yet been fully developed for the time-ordered biological requirements of vascular stents. The first month after vascular stent implantation, the pathological changes in the injured vascular tissue are complex and time-ordered. Therefore, vascular stents possess time-dependent biofunctions with early phase anticoagulant and anti-inflammatory properties. In the later stage, inhibitory effects on smooth muscle cell proliferation and the promotion of endothelial cell adhesion might meet the requirements of vascular repair. We fabricated three types of hyaluronic acid nanoparticles (HA-NPs) by subjecting HA and poly(ether imide) to ethyl(dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide coupling reaction. The HA-NPs prepared by HA with a molecular weight of 100 kDa showed the best stability in a hyaluronidase environment. HA-NP composite films (HA-NCFs) were then fabricated by coimmobilizing selected HA-NPs (100 kDa) and HA molecules (100 kDa) through amide reaction on PDA/HD coated 316 L stainless steel surfaces. The detachment behavior of HA-NPs (100 kDa) in PBS for 20 days indicated that the HA-NPs (100 kDa) gradually detached from the surface. In vitro tests (anticoagulant and anti-inflammatory tests, endothelial cells, and smooth muscle cells seeding, and bacterial adhesion test) indicated that the newly fabricated HA-NCFs have inhibitory effects on the adhesion of fibrinogen, platelets, macrophages, bacteria, SMCs, and ECs. As the HA-NPs detached from the surface, the HA-NCFs showed excellent gradual comprehensive biocompatibility, which promoted adhesion and proliferation of ECs while still exerting inhibitory effects on the platelets, macrophages, and SMCs. Finally, in vivo SS wire implantation test (aortic implantation in healthy Sprague-Dawley rats) showed that HA-NCFs possessed anti-inflammatory properties, inhibited the proliferation of smooth muscle cells, and promoted re-endothelialization. In particular, HA-NCFs with time-dependent biofunctions showed better antirestenosis effects than those of surfaces modified with molecular HA, which exhibited constant biocompatibility. This study provides an important basis for the construction of HA-NP composite films with favorable time-dependent biofunctions for the time-ordered biological requirements of vascular stent.

Tailoring of TiO2 films by H2SO4 treatment and UV irradiation to improve anticoagulant ability and endothelial cell compatibility.

Surfaces with dual functions that simultaneously exhibit good anticoagulant ability and endothelial cell (EC) compatibility are desirable for blood contact materials. However, these dual functions have rarely been achieved by inorganic materials. In this study, titanium dioxide (TiO2) films were treated by sulphuric acid (H2SO4) and ultraviolet (UV) irradiation successively (TiO2H2SO4-UV), resulting in good anticoagulant ability and EC compatibility simultaneously. We found that UV irradiation improved the anticoagulant ability of TiO2 films significantly while enhancing EC compatibility, though not significantly. The enhanced anticoagulant ability could be related to the oxidation of surface-adsorbed hydrocarbons and increased hydrophilicity. The H2SO4 treatment improved the anticoagulant ability of TiO2 films slightly, while UV irradiation improved the anticoagulant ability strongly. The enhanced EC compatibility could be related to the increased surface roughness and positive charges on the surface of the TiO2 films. Furthermore, the time-dependent degradation of the enhanced EC compatibility and anticoagulant ability of TiO2H2SO4-UV was observed. In summary, TiO2H2SO4-UV expressed both excellent anticoagulant ability and good EC compatibility at the same time, which could be desirable for blood contact materials. However, the compatibility of TiO2H2SO4-UV with smooth muscle cells (SMCs) and macrophages was also improved. More effort is still needed to selectively improve EC compatibility on TiO2 films for better re-endothelialization.

Effect of the duration of UV irradiation on the anticoagulant properties of titanium dioxide films.

Recently, UV irradiation has been reported as a new approach to significantly improve the anticoagulant properties of titanium dioxide (TiO2) films by suppressing fibrinogen adsorption and platelet adhesion. This study focuses on how fibrinogen adsorption of and platelet adhesion to TiO2 films is affected by the duration of UV irradiation. Furthermore, this study intends to describe the link between the suppression effect and the changes in the TiO2 films nature caused by photogenerated reactive oxygen species (ROS). First, we performed UV irradiation in different atmospheres as model 1 to determine the effect of oxygen gas on the anticoagulant properties of TiO2 films. The results showed that the suppression of platelet adhesion induced by UV irradiation depended on the presence of oxygen gas, indicating that ROS were photogenerated, and the ROS-induced surface change was related to the improvement in the anticoagulant ability. Then, we fabricated three other types of TiO2 samples in air by varying the UV irradiation time: (1) model 2, comprising fully UV-irradiated TiO2 films, (2) model 3, comprising partially UV-irradiated TiO2 films, and (3) model 4, comprising fully UV-irradiated TiO2-Si micropatterns. The results indicated that UV irradiation affected the anticoagulant properties of TiO2 films in a time-dependent manner. UV irradiation on TiO2 films for short duration (e.g., 1 min) evidenced a suppression effect on fibrinogen adsorption and platelet adhesion, an effect that could not be the result of photoinduced superhydrophilicity, increased hydroxyl groups (-OH) number, or decomposition of the adsorbed hydrocarbon. When the UV irradiation time was longer, this suppression effect extended from the surface of the UV-irradiated TiO2 films to the surface of the adjacent masked TiO2 films and the nearby Si surface. This result supported that the suppression effect could be related to the changes in the nature of the TiO2 films that were caused by the photogenerated and diffused ROS. Further, this extension of the suppression effect to the Si surface indicated that the photogenerated ROS could be used to improve the anticoagulant properties of other materials. A prolonged UV irradiation time (e.g., 240 min) may enhance the fibrinogen adsorption of and platelet adhesion to TiO2 films, which could be related to the decomposition of the adsorbed hydrocarbon and the increase in the positive charge. However, when comparing the enhancement effect and the suppression effect, the results showed that the latter was the main one to influence fibrinogen adsorption of and platelet adhesion to TiO2 films. This study provides an important basis for understanding the behavior of UV-irradiated TiO2 films as anticoagulant materials.

Co-culture of endothelial cells and patterned smooth muscle cells on titanium: construction with high density of endothelial cells and low density of smooth muscle cells.

Endothelialization has been considered a promising method to improve the biocompatibility of vascular implanted biomaterials. However, little is known about the anti-coagulation, anti-inflammatory, anti-atherosclerosis and anti-shedding property of the attached endothelial cells (ECs) and the relationship with their bio-environment and material-environment, which are both important evaluations to the cardiovascular biomaterials designed for tissue engineering applications and in vivo implantation. In this in vitro study, a novel co-culture model was built, where vascular smooth muscle cells (SMCs) were cultured on the hyaluronic acid (HA) micro-strip patterned titanium (Ti) surface on a low density to biomimetic the EC pericyte environment. Subsequently, the EC number and its functional factor, including nitric oxide (NO), prostacyclin (PGI2), tissue factor pathway inhibitor (TFPI), thrombomodulin (TM), and the inflammatory induced factor, endothelial leukocyte adhesion molecule-1 (E-selectin) were quantified, respectively. The anti-shedding property was also assessed by the blood flow shear stress (BFSS) acting. The results showed that the novel co-culture model possessed better EC coverage, functional factor release and anti-shedding functions than the control.

The effect of full/partial UV-irradiation of TiO2 films on altering the behavior of fibrinogen and platelets.

Titanium oxide (TiO2) thin film is a potential candidate for the surface modification of blood-contacting devices. It has previously been reported that ultraviolet light (UV) irradiation could alter the biocompatibility of TiO2 films. However, the effect of UV-irradiated TiO2 films on blood compatibility has rarely been reported. This study attempts to determine: (1) whether UV-irradiation of TiO2 films enhances their blood compatibility, (2) the interaction between UV-irradiated TiO2 films, fibrinogen (Fgn), and platelets, especially how Fgn and platelets respond to the geometry of the partially UV-irradiated TiO2 film surface. Anatase TiO2 films were subjected to full and partial UV-irradiation. Full UV-irradiation improved the blood compatibility of TiO2 films by almost completely inhibiting the adhesion and activation of platelets, strongly suppressing the adsorption and conformational change of Fgn, and preventing the formation of fibrin fibers. Additionally, hemolysis was not observed. After partial UV-irradiation, the regions where Fgn adsorption was reduced (Fgn-dark regions) were formed at regions where UV-irradiation had occurred, but were extended in comparison with the UV-irradiated regions, which could be related to the generation and diffusion of reactive oxygen species (ROS) on the UV-irradiated TiO2 surface. It is worthwhile to study how ROS altered the nature of TiO2 films, thereby enhancing their blood compatibility. Furthermore, platelets were found adhering to the Fgn-adsorbed regions (Fgn-bright regions) selectively, suggesting that the inhibition of platelet adhesion could be related to the suppression of Fgn adsorption on the UV-irradiated TiO2 surface. It was also noted that platelet surface coverage (Sp) was not linearly correlated with Fgn-bright region surface coverage (Sf), which indicated that the adhesion and spreading of platelets were regulated by both Sf and the geometry of Fgn.

Research of smooth muscle cells response to fluid flow shear stress by hyaluronic acid micro-pattern on a titanium surface.

The morphology of vascular smooth muscle cells (SMCs) in the normal physiological state depends on cytoskeletal distribution and topology beneath, and presents vertical to the direction of blood flow shear stress (FFSS) although SMCs physiologically are not directly exposed to the shear conditions of blood flow. However, this condition is relevant for arteriosclerotic plaques and the sites of a vascular stent, and little of this condition in vitro has been studied and reported till now. It is unclear what will happen to SMC morphology, phenotype and function when the direction of the blood flow changed. In this paper, the distribution of SMCs in a specific area on Ti surface was regulated by micro-strips of hyaluronic acid (HA). Cell morphology depended on the distribution of the cytoskeleton extending along the micrographic direction. Simulated vascular FFSS was perpendicular or parallel to the direction of the cytoskeleton distribution. Based on investigating the morphology, apoptotic number, phenotypes and functional factors of SMCs, it was obtained that SMCs of vertical groups showed more apoptosis, expressed more contractile types and secreted less TGF-ß1 factor compared with SMCs of parallel groups, the number of ECs cultured by medium from SMCs of parallel groups was larger than vertical groups. This study could help to understand the effect of direction change of FFSS on patterned SMC morphology, phenotype and function.

Perinatal occipital lobe injury in children: analysis of twenty-one cases.

This study used magnetic resonance imaging to analyze causes and clinical courses of pediatric occipital lobe injury. Patients undergoing magnetic resonance imaging for suspected bilateral occipital lobe injury at our Neurodevelopmental Department between July 2007 and June 2011 were included. We evaluated magnetic resonance imaging characteristics, clinical courses, electroencephalogram monitoring, and Denver Development Screen Test scores. Twenty-one infants were examined. Of these, 10 had been born preterm. Thirteen patients demonstrated hypoglycemia. Perinatal period hypoglycemia comprised the most common cause (71.4%) of occipital brain injury. Visual abnormalities were evident in 18 patients. Seventeen (80.9%) patients manifested epilepsy. Infantile spasms were observed in 13 cases (76.5%). According to Denver Development Screen Test assessment, 17 patients demonstrated delayed motor development. Motor function and language improved in 10 patients after effective control of their seizures. Hypoglycemia constitutes the most common cause of occipital injury in infants. Visual impairment, startle episodes, infantile spasms, and motor developmental delay comprise the most common complications, whereas language function is usually spared.

Tailoring of the titanium surface by immobilization of heparin/fibronectin complexes for improving blood compatibility and endothelialization: an in vitro study.

To improve the blood compatibility and endothelialization simultaneously and to ensure the long-term effectiveness of the cardiovascular implants, we developed a surface modification method, enabling the coimmobilization of biomolecules to metal surfaces. In the present study, a heparin and fibronectin mixture (Hep/Fn) covalently immobilized on a titanium (Ti) substrate for biocompatibility was investigated. Different systems [N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide and N-hydroxysuccinimide, electrostatic] were used for the formation of Hep/Fn layers. Atomic force microscopy (AFM) showed that the roughness of the silanized Ti surface decreased after the immobilization of Hep/Fn. Fourier transform infrared spectroscopy (FTIR), Toluidine Blue O (TBO) test, and immunochemistry assay showed that Hep/Fn mixture was successfully immobilized on Ti surface. Blood compatibility tests (hemolysis rate, APTT, platelet adhesion, fibrinogen conformational change) showed that the coimmobilized films of Hep/Fn mixture reduced blood hemolysis rate, prolonged blood coagulation time, reduced platelets activation and aggregation, and induced less fibrinogen conformational change compared with a bare Ti surface. Endothelial cell (EC) seeding showed more EC with better morphology on pH 4 samples than on pH 7 and EDC/NHS samples, which showed rounded and aggregated cells. Systematic evaluation showed that the pH 4 samples also had much better blood compatibility. All results suggest that the coimmobilized films of Hep/Fn can confer excellent antithrombotic properties and with good endothelialization. We envisage that this method will provide a potential and effective solution for the surface modification of cardiovascular implant materials.

Coimmobilization of heparin/fibronectin mixture on titanium surfaces and their blood compatibility.

Coimmobilization as a versatile biomodification technique has been widely used in the development of biomimetic materials with superior mechanical and biological properties. In this study, a mixture of heparin and fibronectin (Hep/Fn) was tested for its hemocompatibility after either physisorption or covalent coimmobilization to a titanium (Ti) substrate. The process of substrate activation and film deposition was associated with an increase of roughness; successful immobilization in both cases was demonstrated by FTIR. The immobilized heparin amount was probed by toluidine blue O binding, fibronectin by immunochemistry. Both molecules had slightly higher concentrations on the physisorbed film than after covalent coimmobilization. Plasmatic coagulation activation, tested as activated partial thromboplastin time APTT, and platelet adhesion were significantly improved on the covalently coimmobilized samples than on the physisorbed or blank ones. All these results suggest that the covalent coimmobilization of heparin with fibronectin improved the anticoagulant activity of heparin and caused a favorable blood compatibility. We envisage that this method will provide a potential and effective selection for biomaterials surface modification.