Engineered Leukocyte Biomimetic Colorimetric Sensor Enables High-Efficient Detection of Tumor Cells Based on Bioorthogonal Chemistry.

Accurate detection of heterogeneous circulating tumor cells (CTCs) is critical as they can make tumor cells more aggressive, drug-resistant, and metastasizing. Although the leukocyte membrane coating strategy is promising in meeting the challenge of detecting heterogeneous CTCs due to its inherent antiadhesive properties, it is still limited by the reduction or loss of expression of known markers. Bioorthogonal glycol-metabolic engineering is expected to break down this barrier by feeding the cells with sugar derivatives with a unique functional group to establish artificial targets on the surface of tumor cells. Herein, an engineered leukocyte biomimetic colorimetric sensor was accordingly fabricated for high-efficient detection of heterogeneous CTCs. Compared with conventional leukocyte membrane coating, the sensor could covalently bound to the heterogeneous CTCs models fed with Ac4ManNAz in vitro through the synergy of bioorthogonal chemistry and metabolic glycoengineering, ignoring the phenotypic changes of heterogeneous CTCs. Meanwhile, a sandwich structure composed of leukocyte biomimetic layer/CTCs/MoS2 nanosheet was formed for visual detection of HeLa cells as low as 10 cells mL-1. Overall, this approach can overcome the dependence of conventional cell membrane biomimetic technology on specific cell phenotypes and provide a new viewpoint to highly efficiently detect heterogeneous CTCs.

Optimizing the Biocompatibility of PLLA Stent Materials: Strategy with Biomimetic Coating.

Background: Poly-L-lactic acid (PLLA) stents have broad application prospects in the treatment of cardiovascular diseases due to their excellent mechanical properties and biodegradability. However, foreign body reactions caused by stent implantation remain a bottleneck that limits the clinical application of PLLA stents. To solve this problem, the biocompatibility of PLLA stents must be urgently improved. Albumin, the most abundant inert protein in the blood, possesses the ability to modify the surface of biomaterials, mitigating foreign body reactions-a phenomenon described as the "stealth effect". In recent years, a strategy based on albumin camouflage has become a focal point in nanomedicine delivery and tissue engineering research. Therefore, albumin surface modification is anticipated to enhance the surface biological characteristics required for vascular stents. However, the therapeutic applicability of this modification has not been fully explored. Methods: Herein, a bionic albumin (PDA-BSA) coating was constructed on the surface of PLLA by a mussel-inspired surface modification technique using polydopamine (PDA) to enhance the immobilization of bovine serum albumin (BSA). Results: Surface characterization revealed that the PDA-BSA coating was successfully constructed on the surface of PLLA materials, significantly improving their hydrophilicity. Furthermore, in vivo and in vitro studies demonstrated that this PDA-BSA coating enhanced the anticoagulant properties and pro-endothelialization effects of the PLLA material surface while inhibiting the inflammatory response and neointimal hyperplasia at the implantation site. Conclusion: These findings suggest that the PDA-BSA coating provides a multifunctional biointerface for PLLA stent materials, markedly improving their biocompatibility. Further research into the diverse applications of this coating in vascular implants is warranted.

Tumor microenvironment targeting for glioblastoma multiforme treatment via hybrid cell membrane coating supramolecular micelles.

Glioblastoma multiforme (GBM) is one of the most common primary intracranial tumors in the central nervous system with poor prognosis, high invasiveness, risk of recurrence and low survival rate. Thus, it is urgent and vital to develop drug effective delivery systems that efficiently to traverse the blood-brain barrier and targeted transport therapeutic agents into the GBM tumor site for the treatment of brain tumors. Recently, amphiphilic cucurbit[7]uril-polyethylene glycol-hydrophobic Chlorin e6 (CB[7]-PEG-Ce6) polymer was designed, prepared, and self-assembled into micells (CPC) in an aqueous solution, and chemo drug methyl-triazeno-imidazole-carboxamide (MTIC), loaded into the cavity of CB[7] was subsequently coated with hybrid membrane mUMH (HMC3 membrane: macrophage membrane: U87MG membrane = 1:1:2) to afford mUMH@CPC@MTIC. The surface hybrid membrane mUMH potentially enhance the targeted delivery of CPC@MTIC to GBM tissue. Bioactive MTIC was released from the cavity of CB[7] in response to the high spermine level in GBM tumor microenvironments for effective tumor chemotherapy. The biomimetic mUMH@CPC@MTIC exhibited superior antitumor efficacy against GBM in mice. These findings provide new strategies for the design of biomimetic nanoparticle-based drug delivery systems and promising therapy of GBM.

Colorectal cancer cell exosome and cytoplasmic membrane for homotypic delivery of therapeutic molecules.

Colorectal cancer (CRC) is one of the most common causes of death in the world. The multi-drug resistance, especially in metastatic colorectal cancer, drives the development of new strategies that secure a positive outcome and reduce undesirable side effects. Nanotechnology has made an impact in addressing some pharmacokinetic and safety issues related to administration of free therapeutic agents. However, demands of managing complex biointerfacing require equally complex methods for introducing stimuli-responsive or targeting elements. In order to procure a more efficient solution to the overcoming of biological barriers, the physiological functions of cancer cell plasma and exosomal membranes provided the source of highly functionalized coatings. Biomimetic nanovehicles based on colorectal cancer (CRC) membranes imparted enhanced biological compatibility, immune escape and protection to diverse classes of therapeutic molecules. When loaded with therapeutic load or used as a coating for other therapeutic nanovehicles, they provide highly efficient and selective cell targeting and uptake. This review presents a detailed overview of the recent application of homotypic biomimetic nanovehicles in the management of CRC. We also address some of the current possibilities and challenges associated with the CRC membrane biomimetics.

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.

Phase-transited lysozyme nanofilm with co-immobilized copper ion and heparin as cardiovascular stent multifunctional coating.

Cardiovascular metal stents have shown potential in the treatment of coronary artery disease using percutaneous coronary intervention. However, thrombosis, endothelialization, and new atherosclerosis after stent implantation remain unsolved problems. Herein, a multifunctional coating material based on phase-transited lysozyme was developed to promote stent endothelialization and simultaneously reduce thrombus events by embedding moieties of heparin and co-immobilized copper ions for in-situ catalyzing nitric oxide (NO) generation. The lysozyme-based biomimetic coating is compatible with blood and enables facile loading and sustainable release of copper ions to produce NO with donors via catalytic reaction. The novel coating strategy displayed several bio-effects of anti-thrombosis; it synergistically promoted endothelial cell growth and inhibited smooth muscle cell growth. Thus, this systemic in vitro study will provide a foundation for developing multifunctional cardiovascular stents in clinical settings.

Multifunctional Biomimetic Composite Coating with Antireflection, Self-Cleaning and Mechanical Stability.

Antireflective and self-cleaning coatings have attracted increasing attention in the last few years due to their promising and wider applications such as stealth, display devices, sensing, and other fields. However, existing antireflective and self-cleaning functional material are facing problems such as difficult performance optimization, poor mechanical stability, and poor environmental adaptability. Limitations in design strategies have severely restricted coatings' further development and application. Fabrication of high-performance antireflection and self-cleaning coatings with satisfactory mechanical stability remain a key challenge. Inspired by the self-cleaning performance of nano-/micro-composite structure on natural lotus leaves, SiO2/PDMS/matte polyurethane biomimetic composite coating (BCC) was prepared by nano-polymerization spraying technology. The BCC reduced the average reflectivity of the aluminum alloy substrate surface from 60% to 10%, and the water contact angle (CA) was 156.32 ± 0.58°, illustrating the antireflective and self-cleaning performance of the surface was significantly improved. At the same time, the coating was able to withstand 44 abrasion tests, 230 tape stripping tests, and 210 scraping tests. After the test, the coating still showed satisfactory antireflective and self-cleaning properties, indicating its remarkable mechanical stability. In addition, the coating also displayed excellent acid resistance, which has important value in aerospace, optoelectronics, industrial anti-corrosion, etc.

Influence of alumina substrates open porosity on calcium phosphates formation produced by the biomimetic method.

We evaluated the influence of the open porosity of alumina (Al2O3) substrates on the phase formation of calcium phosphates deposited onto it surface. The Al2O3 substrates were prepared with different porosities by the foam-gelcasting method associated with different amounts of polyethylene beads. The substrates were coated biomimetically for 14 and 21 days of incubation in a simulated body fluid (SBF). Scanning electron microscopy characterisation and X-ray computed microtomography showed that the increase in the number of beads provided an increase in the open porosity. The X-ray diffraction and infrared spectroscopy showed that the biomimetic method was able to form different phases of calcium phosphates. It was observed that the increase in the porosity favoured the formation of ß-tricalcium phosphate for both incubation periods. The incubation period and the porosity of the substrates can influence the phases and the amount of calcium phosphates formed. Thus, it is possible to target the best application for the biomaterial produced.

SERS Investigation on Oligopeptides Used as Biomimetic Coatings for Medical Devices.

The surface-enhanced Raman scattering (SERS) spectra of three amphiphilic oligopeptides derived from EAK16 (AEAEAKAK)2 were examined to study systematic amino acid substitution effects on the corresponding interaction with Ag colloidal nanoparticles. Such self-assembling molecular systems, known as "molecular Lego", are of particular interest for their uses in tissue engineering and as biomimetic coatings for medical devices because they can form insoluble macroscopic membranes under physiological conditions. Spectra were collected for both native and gamma-irradiated samples. Quantum mechanical data on two of the examined oligopeptides were also obtained to clarify the assignment of the prominent significative bands observed in the spectra. In general, the peptide-nanoparticles interaction occurs through the COO- groups, with the amide bond and the aliphatic chain close to the colloid surface. After gamma irradiation, mimicking a free oxidative radical attack, the SERS spectra of the biomaterials show that COO- groups still provide the main peptide-nanoparticle interactions. However, the spatial arrangement of the peptides is different, exhibiting a systematic decrease in the distance between aliphatic chains and colloid nanoparticles.

Unraveling the Mechanism and Kinetics of Binding of an LCI-eGFP-Polymer for Antifouling Coatings.

The ability of proteins to adsorb irreversibly onto surfaces opens new possibilities to functionalize biological interfaces. Herein, the mechanism and kinetics of adsorption of protein-polymer macromolecules with the ability to equip surfaces with antifouling properties are investigated. These macromolecules consist of the liquid chromatography peak I peptide from which antifouling polymer brushes are grafted using single electron transfer-living radical polymerization. Surface plasmon resonance spectroscopy reveals an adsorption mechanism that follows a Langmuir-type of binding with a strong binding affinity to gold. X-ray reflectivity supports this by proving that the binding occurs exclusively by the peptide. However, the lateral organization at the surface is directed by the cylindrical eGFP. The antifouling functionality of the unimolecular coatings is confirmed by contact with blood plasma. All coatings reduce the fouling from blood plasma by 8894% with only minor effect of the degree of polymerization for the studied range (DP between 101 and 932). The excellent antifouling properties, combined with the ease of polymerization and the straightforward coating procedure make this a very promising antifouling concept for a multiplicity of applications.

Universal and Switchable Omni-Repellency of Liquid-Infused Surfaces for On-Demand Separation of Multiphase Liquid Mixtures.

Mixtures of immiscible liquids are commonly found in the scenarios of environmental protection and many industrial applications. Compared to widely explored water-oil mixtures, small differences in the surface energy of organic liquids, especially for those in multiphase mixtures, make their separation a formidable challenge. Here, a family of versatile coatings based on the reactions between plant polyphenols and 3-aminopropyl triethoxysilane is introduced to regulate the wetting behavior of substrates by forming stable liquid-infused interfaces. The key finding is that when a coated substrate is prewetted with a liquid forming a stable liquid-infused interface, it becomes repellent to any other immiscible liquids. This phenomenon is independent of the surface energy of the initial wetting liquid. This exclusive wetting behavior can lead to distinctive repellency toward almost any liquid by the infusion of an immiscible liquid, even if the difference of surface energy and dielectric constant of a liquid pair is as small as 2.0 mJ m-2 and 1.8, respectively, resulting in universal and switchable omni-repellency. Of particular importance is that the as-prepared coating makes possible the on-demand separation of multiphase liquid mixtures by both continuous membrane filtration and static absorption, presenting a green and cost-effective approach to addressing this major environmental and industrial challenge.

Self-adhesive lubricated coating for enhanced bacterial resistance.

Limited surface lubrication and bacterial biofilm formation pose great challenges to biomedical implants. Although hydrophilic lubricated coatings and bacterial resistance coatings have been reported, the harsh and tedious synthesis greatly compromises their application, and more importantly, the bacterial resistance property has seldom been investigated in combination with the lubrication property. In this study, bioinspired by the performances of mussel and articular cartilage, we successfully synthesized self-adhesive lubricated coating and simultaneously achieved optimal lubrication and bacterial resistance properties. Additionally, we reported the mechanism of bacterial resistance on the nanoscale by studying the adhesion interactions between biomimetic coating and hydrophilic/hydrophobic tip or living bacteria via atomic force microscopy. In summary, the self-adhesive lubricated coating can effectively enhance lubrication and bacterial resistance performances based on hydration lubrication and hydration repulsion, and represent a universal and facial strategy for surface functionalization of biomedical implants.

Biomimetic in situ precipitation of calcium phosphate containing silver nanoparticles on zirconia ceramic materials for surface functionalization in terms of antimicrobial and osteoconductive properties.

OBJECTIVE: Zirconia is commonly used for manufacturing of dental implants thanks to its excellent mechanical, biological and aesthetic properties. However, its bioinertness inhibits bonding with the surrounding hard tissue and other surface interactions. In our study, we present a method for multifunctionalization of zirconia surface to improve its osseointegration and to minimize the infection risks. METHODS: For this reason, we introduced antibacterial and bioactive properties to zirconia surfaces by calcium phosphate biomimetic coating. The samples were incubated in vials in horizontal and vertical position in concentrated simulated body fluid (SBF) containing 0.1, 0.5, and 3 g/L of silver nanoparticles (Ag-NPs) and then were tested for their structure, surface properties, cytocompatibility and antibacterial properties. RESULTS AND SIGNIFICANCE: The results demonstrated that our method is suitable to introduce Ag-NPs at different concentrations into the calcium phosphate layer, i.e. from 0.05-26.6 atom% as shown by EDX. According to the results of CFU-assay these coatings exhibited antibacterial properties against S. aureus and E. coli in correlation with the concentration of Ag-NP. The potential cytotoxicity of the coated samples was determined by AlamarBlue® assay and live/dead staining of MG63 osteoblast-like cells in direct contact and by testing the extracts from the materials. Only samples containing 0.05 atom% Ag-NPs, i.e. incubated in vertical position at SBF with 0.01 g/L Ag-NPs, were found cytocompatible in direct contact with MG63 cells. On the contrary in the indirect tests, the extracts from all the materials were found cytocompatible. This method could allow developing the completely new material group, exhibiting not only one but several biological properties, which can improve osseointegration and minimize infection risks.

Biomimetic engineering endothelium-like coating on cardiovascular stent through heparin and nitric oxide-generating compound synergistic modification strategy.

Co-immobilization of two or more molecules with different and complementary functions to prevent thrombosis, suppress smooth muscle cell (SMC) proliferation, and support endothelial cell (EC) growth is generally considered to be promising for the re-endothelialization on cardiovascular stents. However, integration of molecules with distinct therapeutic effects does not necessarily result in synergistic physiological functions due to the lack of interactions among them, limiting their practical efficacy. Herein, we apply heparin and nitric oxide (NO), two key molecules of the physiological functions of endothelium, to develop an endothelium-mimetic coating. Such coating is achieved by sequential conjugation of heparin and the NO-generating compound selenocystamine (SeCA) on an amine-bearing film of plasma polymerized allylamine. The resulting surface combines the anti-coagulant (anti-FXa) function provided by the heparin and the anti-platelet activity of the catalytically produced NO. It also endows the stents with the ability to simultaneously up-regulate α-smooth muscle actin (α-SMA) expression and to increase cyclic guanylate monophosphate (cGMP) synthesis of SMC, thereby significantly promoting their contractile phenotype and suppressing their proliferation. Importantly, this endothelium-biomimetic coating creates a favorable microenvironment for EC over SMC. These features impressively improve the antithrombogenicity, re-endothelialization and anti-restenosis of vascular stents in vivo.

Enhanced biocompatibility and improved osteogenesis of coralline hydroxyapatite modified by bone morphogenetic protein 2 incorporated into a biomimetic coating.

OBJECTIVES: (1) To determine whether the biocompatibility of coralline hydroxyapatite (CHA) granules could be improved by using an octacalcium phosphate (OCP) coating layer, and/or functionalized with bone morphogenetic protein 2 (BMP-2), and (2) to investigate if BMP-2 incorporated into this coating is able to enhance its osteoinductive efficiency, in comparison to its surface-adsorbed delivery mode. METHODS: CHA granules (0.25 g per sample) bearing a coating-incorporated depot of BMP-2 (20 µg/sample) together with the controls (CHA bearing an adsorbed depot of BMP-2; CHA granules with an OCP coating without BMP-2; pure CHA granules) were implanted subcutaneously in rats (n = 6 animals per group). Five weeks later, the implants were retrieved for histomorphometric analysis to quantify the volume of newly generated bone, bone marrow, fibrous tissue and foreign body giant cells (FBGCs). The osteoinductive efficiency of BMP-2 and the rates of CHA degradation were also determined. RESULTS: The group with an OCP coating-incorporated depot of BMP-2 showed the highest volume and quality or bone, and the highest osteoinductive efficacy. OCP coating was able to reduce inflammatory responses (improve biocompatibility), and also simple adsorption of BMP-2 to CHA achieved this. CONCLUSIONS: The biocompatibility of CHA granules (reduction of inflammation) was significantly improved by coating with a layer of OCP. Pure surface adsorption of BMP-2 to CHA also reduced inflammation. Incorporation of BMP-2 into the OCP coatings was associated with the highest volume and quality of bone, and the highest biocompatibility degree of the CHA granules. CLINICAL SIGNIFICANCE: Higher osteoinductivity and improved biocompatibility of CHA can be obtained when a layer of BMP-2 functionalized OCP is deposited on the surfaces of CHA granules.

Mussel-inspired dopamine-CuII coatings for sustained in situ generation of nitric oxide for prevention of stent thrombosis and restenosis.

Nitric oxide (NO) is a highly potent, yet short-lived bioactive molecule with a broad spectrum of physiological functions. Continuous and controllable in situ generation of NO from vascular stent surface can effectively prevent restenosis and thrombosis after its implantation. In this study, inspired by the adhesion and protein cross-linking in the mussel byssus, through immersing the stents into an aqueous solution with dopamine (DA) and copper ions (CuII), we developed a one-step metal-catecholamine assembled strategy to prepare a durable in situ NO-generating biomimetic coating (DA-CuII). Due to the high NO catalytic efficacy and robust chelation of CuII into the DA-CuII network, the coated stents exhibited excellent hemocompatibility. The coating also catalytically decomposed endogenous S-nitrosothiols (RSNOs) from fresh blood, and locally generated NO for over 30 days with a flux comparable to its physiological range (0.5-4 × 10-10 mol × cm-2 × min-1). Moreover, the optimized biomimetic coatings displayed specific cell selectivity to significantly enhance endothelial cell (EC) growth while substantially inhibit smooth muscle cell (SMC) growth and migration. This feature impressively promoted regeneration of a new endothelial cell layer after stent implantation, hence improved the anti-thrombogenic and anti-restenosis qualities of vascular stents in vivo. We envision that our long-term in situ NO-generating coatings could serve as biosurfaces for long-term prevention of stent thrombosis and restenosis.

The kinetics and mechanism of bone morphogenetic protein 2 release from calcium phosphate-based implant-coatings.

Biomimetically deposited calcium phosphate-based coatings of prostheses can serve as a vehicle for the targeted delivery of growth factors to the local implant environment. Based on indirect evidence in previous studies we hypothesize that such agents are liberated gradually from the coating via a cell-mediated degradation. In the present study, we tested this hypothesis by investigating the release mechanism and its kinetics by use of a radiolabeled osteogenic agent (131 I-BMP-2) under conditions in which native cell populations with a coating-degradative potential were either absent or present. The release of 131 I-BMP-2 was monitored for 5 weeks, either in vitro or after implantation at an ectopic (subcutaneous) site in rats in vivo. Only from implants that bore a coating-incorporated depot of bone morphogenetic protein 2 (BMP-2) was the agent released slowly and steadily over 5 weeks, that is, 50% of the loaded dose was liberated in vivo (5 to 10% weekly), as against 14.6% in vitro (less than 1% weekly). The coatings bearing an incorporated depot of BMP-2 underwent significant cell-mediated degradation, whereas under cell-free conditions no degradation occurred, and the spontaneous release of BMP-2 was negligible. Our findings confirm this carrier system to be a suitable vehicle for the sustained and cell-mediated delivery of BMP-2. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2363-2371, 2018.

Surface modification using the biomimetic method in alumina-zirconia porous ceramics obtained by the replica method.

The modification of biomaterials approved by the Food and Drug Administration could be an alternative to reduce the period of use in humans. Porous bioceramics are widely used as support structures for bone formation and repair. This composite has essential characteristics for an implant, including good mechanical properties, high chemical stability, biocompatibility and adequate aesthetic appearance. Here, three-dimensional porous scaffolds of Al2 O3 containing 5% by volume of ZrO2 were produced by the replica method. These scaffolds had their surfaces chemically treated with phosphoric acid and were coated with calcium phosphate using the biomimetic method simulated body fluid (SBF, 5×) for 14 days. The scaffolds, before and after biomimetic coating, were characterized mechanically, morphologically and structurally by axial compression tests, scanning electron microscopy, microtomography, apparent porosity, X-ray diffractometry, near-infrared spectroscopy, inductively coupled plasma optical emission spectroscopy, energy dispersive X-ray spectroscopy and reactivity. The in vitro cell viability and formation of mineralization nodules were used to identify the potential for bone regeneration. The produced scaffols after immersion in SBF were able to induce the nodules formation. These characteristics are advantaged by the formation of different phases of calcium phosphates on the material surface in a reduced incubation period. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2615-2624, 2018.

Effect of titania content and biomimetic coating on the mechanical properties of the Y-TZP/TiO2 composite.

OBJECTIVE: To investigate the effect of titania addition (0, 10 and 30mol%) on the microstructure, relative density, Young's modulus (E), Poisson's ratio (υ), mechanical properties (flexural strength, σf, and Weibull modulus, m) of a Y-TZP/TiO2 composite. The effect of the presence of a biomimetic coating on the microstructure and mechanical properties was also evaluated. METHODS: Y-TZP (3mol% of yttria) and Y-TZP/TiO2 composite (10 or 30mol% of titania) were synthesized by co-precipitation. The powders were pressed and sintered at 1400°C/2h. The surfaces, with and without biomimetic coating, were characterized by X-ray diffraction analysis and scanning electron microscopy. The relative density was measured by the Archimedes' principle. E and υ were measured by ultrasonic pulse-echo method. For the mechanical properties the specimens (n=30 for each group) were tested in a universal testing machine. RESULTS: Titania addition increased the grain size of the composite and caused a significant decrease in the flexural strength (in MPa, control 815.4a; T10 455.7b and T30 336.0c), E (in GPa, control 213.4a; T10 155.8b and T30 134.0c) and relative density (control 99.0%a; T10 94.4%c and T30 96.3%b) of the Y-TZP/TiO2 composite. The presence of 30% titania caused substantial increase in m and υ. Biomimetic coating did not affect the mechanical properties of the composite. SIGNIFICANCE: The Y-TZP/TiO2 composite coated with a layer of CaP has great potential to be used as implant material. Although addition of titania affected the properties of the composite, the application of a biomimetic coating did not jeopardize its reliability.

Sustained release of growth hormone and sodium nitrite from biomimetic collagen coating immobilized on silicone tubes improves endothelialization.

Biocompatibility of biomedical devices can be improved by endothelialization of blood-contacting parts mimicking the vascular endothelium's function. Improved endothelialization might be obtained by using biomimetic coatings that allow local sustained release of biologically active molecules, e.g. anti-thrombotic and growth-inducing agents, from nanoliposomes. We aimed to test whether incorporation of growth-inducing nanoliposomal growth hormone (nGH) and anti-thrombotic nanoliposomal sodium nitrite (nNitrite) into collagen coating of silicone tubes enhances endothelialization by stimulating endothelial cell proliferation and inhibiting platelet adhesion. Collagen coating stably immobilized on acrylic acid-grafted silicone tubes decreased the water contact angle from 102° to 56°. Incorporation of 50 or 500nmol/ml nNitrite and 100 or 1000ng/ml nGH into collagen coating decreased the water contact angle further to 48°. After 120h incubation, 58% nitrite and 22% GH of the initial amount of sodium nitrite and GH in nanoliposomes were gradually released from the nNitrite-nGH-collagen coating. Endothelial cell number was increased after surface coating of silicone tubes with collagen by 1.6-fold, and with nNitrite-nGH-collagen conjugate by 1.8-3.9-fold after 2days. After 6days, endothelial cell confluency in the absence of surface coating was 22%, with collagen coating 74%, and with nNitrite-nGH-collagen conjugate coating 83-119%. In the absence of endothelial cells, platelet adhesion was stimulated after collagen coating by 1.3-fold, but inhibited after nNitrite-nGH-collagen conjugate coating by 1.6-3.7-fold. The release of anti-thrombotic prostaglandin I2 from endothelial cells was stimulated after nNitrite-nGH-collagen conjugate coating by 1.7-2.2-fold compared with collagen coating. Our data shows improved endothelialization and blood compatibility using nNitrite-nGH-collagen conjugate coating on silicone tubes suggesting that these coatings are highly suitable for use in blood-contacting parts of biomedical devices.