Plasma Protein Adsorption Research Articles

Transferrin Protein Corona-Targeted Codelivery of Tirapazamine and IR820 Facilitates Efficient PDT-Induced Hypoxic Chemotherapy on 4T1 Breast Cancer.

Protein corona (PC) formation confers novel biological properties to the original nanomaterial, impeding its uptake and targeting efficacy in cells and tissues. Although many studies discussing PC formation have focused on inert proteins that may inhibit the function of nanomaterials, some functional plasma proteins with intrinsic targeting capabilities can also be adsorbed to the surface of nanomaterials, with active ligand properties to improve the targeting ability. In this approach, nanomaterials are surface-engineered to promote the adsorption of specific functional plasma proteins that are directly targeted to transport nanomaterials to the target site. In this study, T10 peptide-modified liposomes were employed to construct an in situ transferrin (Tf) PC-mediated liposome carrying a hypoxia-sensitive chemotherapy drug (tirapazamine, TPZ) and a photosensitizer (indocyanine green, IR820). The water-soluble drug TPZ was encapsulated in mesoporous silica nanoparticles (MSNs) and coated with IR820 (IR)-loaded liposome. Lipid-coated MSNs can inhibit aggregation in the body and significantly reduce the rapid release of water-soluble drugs, resulting in improved system stability and sustained release. Upon entering the in vivo circulation, T10 bound specifically to Tf in plasma to form an in situ Tf liposome-PC complex with enhanced targeting efficacy compared to traditional ligand-modified active-targeting strategies. However, large-sized PC particles faced challenges in penetrating deep into tumor tissues. IR could kill tumors through photodynamic therapy (PDT) and elicit complementary antitumor effects with the hypoxia-sensitive drug TPZ. This study demonstrates the novel design of in situ PC-mediated multifunctional liposomes for hypoxia-activated chemotherapy combined with PDT, a promising approach to cancer therapy.

Effect of Uremic Toxins and Methoxy-PEO Chain Density on Plasma Protein Adsorption.

Protein adsorption can direct the host response to blood-contacting biomaterials. Poly(ethylene oxide) (PEO) is commonly employed to minimize nonspecific protein adsorption. Although chain density has been observed to play a role in the inherent resistance of protein adsorption by end-tethered films of PEO, only a few papers correlate the change in PEO chain densities with the adsorbed plasma protein composition. Almost all studies rely upon blood from healthy patients for these studies even though they are applied to the unhealthy. In the case of patients with kidney failure, there is a remarkable change in the blood composition due to retained metabolites. In the pursuit of personalized dialysis, we must address this dearth in the literature regarding the effect of metabolite accumulation in the blood compartment on the adsorption of protein to blood-contacting biomaterials. To this end, surface films of different methoxy-PEO (mPEO) chain densities were used to evaluate the changes in adsorbed proteins in the presence of uremic metabolites (i.e., uremic toxins). End-tethered mPEO films were characterized using contact angles, ellipsometry, and X-ray photoelectron spectroscopy. Plasma protein adsorption was conducted with and without uremic toxins commonly found in patients with end stage kidney disease, and the adsorbed protein profile was identified using immunoblots. It was found that the presence of uremic toxins led to a notable increase in the adsorption of almost all of the proteins. It was evident that while chain density plays a role in overall protein resistance, the effect of uremic toxins led to substantial increases in adsorbed proteins and needs to be considered when designing next-generation blood-contacting materials.

Polystyrene nanoplastics enhance thrombosis through adsorption of plasma proteins

Plastic products offer remarkable convenience for modern life. However, growing concerns are emerging regarding the potential health hazards posed by nanoplastics, which formed as plastics break down. Currently, the biological effects and mechanisms induced by nanoplastics are largely underexplored. In this study, we report that polystyrene nanoplastics can enter the bloodstream and enhance thrombus formation. Our findings show that polystyrene nanoplastics adsorb plasma proteins, particularly coagulation factor XII and plasminogen activator inhibitor-1, play a key role in this process, as demonstrated by proteomics, bioinformatic analyses, and molecular dynamics simulations. The adsorption of these proteins by nanoplastics is an essential factor in thrombosis enhancement. This newly uncovered pathway of protein adsorption leading to enhanced thrombosis provides new insights into the biological effects of nanoplastics, which may inform future safety and environmental risk assessment of plastics.

Plasma Protein Adsorption on Melphalan Prodrug Bearing Liposomes - Bare, Stealth, and Targeted

Background: Plasma protein binding is inevitable for nanomaterials injected into blood circulation. For liposomes, this process is affected by the lipid composition of the bilayer. Membrane constituents and their ratio define liposome characteristics, namely, surface charge and hydrophobicity, which drive protein adsorption. Roughly 30 years ago, the correlation between the amount of bound proteins and the resulting circulation time of liposomes was established by S. Semple, A. Chonn, and P. Cullis. Here, we have estimated ex vivo plasma protein binding, primarily to determine the impact of melphalan prodrug inclusion into bilayer on bare, PEGylated (stealth), and Sialyl Lewis X (SiaLeX)-decorated liposomes. Experimental: Liposomes were allowed to bind plasma proteins for 15 minutes, then liposome-protein complexes were isolated, and protein and lipid quantities were assessed in the complexes. In addition, the uptake by activated HUVEC cells was evaluated for SiaLeX-decorated liposomes. Results:: Melphalan moieties on the bilayer surface enrich protein adsorption compared to pure phosphatidylcholine sample. Although PEG-lipid had facilitated a significant decrease in protein adsorption in the control sample, when prodrug was added to the composition, the degree of pro-tein binding was restored to the level of melphalan liposomes without a stealth barrier. A similar effect was observed for SiaLeX-decorated liposomes. Conclusion: None of the compositions reported here should suffer from quick elimination from circulation, according to the cut-off values introduced by Cullis and colleagues. Nevertheless, the amount of bound proteins is sufficient to affect biodistribution, namely, to impair receptor recog-nition of SiaLeX and reduce liposome uptake by endothelial cells.

Hemocompatibility of Albumin-Modified Magnetic Nanoparticles.

Kidney failure leads to the accumulation of metabolites in the blood compartment. This build-up of metabolites has been associated with increased mortality and morbidity in these patients; thus, these metabolites are commonly called uremic toxins. The retention of some uremic toxins in the blood results from a strong interaction with serum albumin, preventing their clearance using standard hemodialysis techniques. Adsorbents are considered the next-generation technology for clearing uremic toxins from the blood, and iron oxide magnetic nanoparticles are a promising material due to a high surface area that is easily modified and the ability to remove them from blood with an external magnetic field. Plasma protein adsorption and clot formation kinetics were determined for unmodified and albumin-modified iron oxide magnetic nanoparticles. Albumin was selected because it can bind uremic toxins, and it is commonly used to passivate surfaces. Coatings were formed and characterized using transmission electron microscopy, thermogravimetric analysis, and zeta-potential analysis. Clotting kinetics, total protein assays, and immunoblots were used to analyze the effect surface modification has on protein adsorption events. Unmodified nanoparticles showed rapid clotting and more adsorbed protein compared to albumin-coated iron oxide nanoparticles. Immunoblots show that modified particles showed changes in albumin, protein C, Immunoglobulin G, transferrin, fibrinogen, α1-antitrypsin, vitronectin, plasminogen, prothrombin, and antithrombin levels compared to unmodified controls. The hemocompatibility of adsorbent materials is essential to their clinical application in clearing the blood of uremic toxins.

Synergistic coating of Laponite swollen-layer and heparin composite for enhanced antifouling and antithrombotic performance

When implantable medical devices come into contact with blood, acute thrombosis and inflammation often occur due to the adhesion and denaturation of plasma proteins, ultimately degrading device performance. To address this issue, we developed a gel-like coating with superhydrophilic properties, incorporating a heparin based outer layer designed to minimize foreign body reactions and enhance hemocompatibility. The coating was engineered using a layer-by-layer (LbL) assembly of poly-l-lysine (PLL), laponite (Lap), and heparin (Hep), utilizing electrostatic interactions. The successful formation of stable layers was confirmed by QCM-D analysis. The inner layer, composed of PLL/Lap multilayers, formed a gel-like structure that maintained superhydrophilicity and effectively prevented cell adhesion. The outermost PLL/Hep multilayers significantly suppressed thrombus formation by inhibiting plasma protein and red blood cell adsorption as well as platelet activation. The coating exhibited excellent stability, retaining its superhydrophilic properties and heparin functionality even after 7 days of immersion in DPBS. Additionally, in vitro hemocompatibility and cytocompatibility tests confirmed its non-toxicity and overall biocompatibility. These results highlight the potential application of this coating to various implantable medical devices, providing a robust solution for improving device performance and safety.

Enhanced Solubility and Increased Bioavailability with Engineered Nanocrystals

Abstract: The exploration of nanocrystal technology is currently receiving significant attention in various fields, including therapeutic formulation, clinical formulation, in-vivo and in-vitro correlation research, and related investigations. The domain of nanocrystals in pharmaceutical delivery has received significant interest as a potential solution for the difficulties associated with medications that have low solubility. The nanocrystals demonstrate promise in improving solubility and bioavailability, presenting a potential resolution to significant challenges. Significantly, nanocrystals have exhibited efficacy in the context of oral administration, showcasing prompt absorption due to their quick breakdown, hence fitting with the requirements of medications that necessitate fast commencement of action. In addition, the adaptability of drug nanocrystals encompasses several methods of administration, including oral, parenteral, ophthalmic, cutaneous, pulmonary, and targeted delivery modalities. The observed consistency can be ascribed to the increased solubility of nanocrystals of the medicine, which effectively counteracts the influence of food on the absorption of the drug. Surface modification tactics have a significant influence on insoluble medicines by enhancing hydrophilicity and reducing plasma protein adsorption on the crystal surface. The surface properties of nanocrystals are modified through the utilization of specific surfactants and polymers, which are subsequently incorporated into polymer solutions via high-pressure homogenization procedures. This article encompasses an examination of the drug distribution mechanism, the nanocrystal formulation technology, the therapeutic applications, the potential future developments, and the challenges associated with the solubility and bioavailability of tailored nanocrystals, as discussed in this article. Consequently, it possesses the capacity to provide guidance for future investigations pertaining to nanocrystal technology.

Molecular and Energetic Descriptions of the Plasma Protein Adsorption onto the PVC Surface: Implications for Biocompatibility in Medical Devices.

Protein adsorption on material surfaces plays a key role in the biocompatibility of medical devices. Therefore, understanding the complex interplay of physicochemical factors driving this kind of biofouling is paramount for advancing biomaterial design. In this study, we investigated the interaction of the most prominent plasma proteins with polyvinyl chloride (PVC) as one of the ubiquitous materials in medical devices. Through molecular docking, we identified human serum albumin (HSA) as a plasma protein with the highest affinity for adsorption onto the PVC surface with the binding energy of -25.9 kJ mol-1. Subsequently, utilizing triplicate molecular dynamics (MD) simulations (0.5 μs each), we quantitatively analyzed the interactions between HSA and PVC, probing potential structural changes in the protein upon adsorption. Our findings revealed that water-mediated hydrogen bonds and van der Waals forces are key contributors in stabilizing HSA onto the surface of PVC without significant alteration to its secondary and tertiary structures. The observed distribution of water molecules further highlights the importance of the hydration layer in facilitating and modulating protein-polymer interactions. We further evaluated the thermodynamic properties governing the adsorption process by calculating the potential of mean force (PMF) along the direction normal to the surface. The computed Gibbs free energy of adsorption at 300 K (-507.4 kJ/mol) indicated a thermodynamically favored and spontaneous process. Moreover, our investigations across different temperatures (290 to 310 K) consistently showed an enthalpy-driven adsorption process.

Dialysis nanocomposite membranes based on carbon nanoforms inhibiting blood plasma protein adsorption.

Protein adsorption on medical devices in contact with blood is a significant issue during renal replacement therapy. Main forces determining fouling are the electrostatic interactions between membrane and charged protein, but the dialysis membrane surface charges can be adjusted by modifying the polymer matrix to decrease the blood plasma protein adsorption. In this study, polysulfone membranes (PSU) were modified by incorporation of carbon nanoparticles such as: multiwall carbon nanotubes (2 wt.% MWCNT), graphene oxide (1 wt.% GO), and graphite (5 wt.% GR) during manufacturing process (nonsolvent-induced phase separation, NIPS). The PSU flat sheet membrane was the reference sample. Observed morphology of nanocomposite membranes was similar (SEM imaging); all of them had finger-like pore structure with unimodal distribution of pore size and similar skin-to-support ratio (1:3). The carbon nanoadditives also influenced the surface wettability: hydrophobicity and surface free energy of membranes increased (polar components of energy were reduced, while the dispersive components were increased). The surface charge of nanocomposite membranes increased, when the polymer matrix has been modified with CNT or GR. This significantly affects the adsorption of proteins such as chicken (CSA) and bovine serum albumin (BSA) and reduces blood clotting on the membrane.

Randomized investigation of increased dialyzer membrane hydrophilicity on hemocompatibility and performance

BackgroundHemodialyzers should efficiently eliminate small and middle molecular uremic toxins and possess exceptional hemocompatibility to improve well-being of patients with end-stage kidney disease. However, performance and hemocompatibility get compromised during treatment due to adsorption of plasma proteins to the dialyzer membrane. Increased membrane hydrophilicity reduces protein adsorption to the membrane and was implemented in the novel FX CorAL dialyzer. The present randomized controlled trial compares performance and hemocompatibility profiles of the FX CorAL dialyzer to other commonly used dialyzers applied in hemodiafiltration treatments.MethodsThis prospective, open, controlled, multicentric, interventional, crossover study randomized stable patients on post-dilution online hemodiafiltration (HDF) to FX CorAL 600, FX CorDiax 600 (both Fresenius Medical Care) and xevonta Hi 15 (B. Braun) each for 4 weeks. Primary outcome was β2-microglobulin removal rate (β2-m RR). Non-inferiority and superiority of FX CorAL versus comparators were tested. Secondary endpoints were RR and/or clearance of small and middle molecules, and intra- and interdialytic profiles of hemocompatibility markers, with regards to complement activation, cell activation/inflammation, platelet activation and oxidative stress. Further endpoints were patient reported outcomes (PROs) and clinical safety.Results82 patients were included and 76 analyzed as intention-to-treat (ITT) population. FX CorAL showed the highest β2-m RR (76.28%), followed by FX CorDiax (75.69%) and xevonta (74.48%). Non-inferiority to both comparators and superiority to xevonta were statistically significant. Secondary endpoints related to middle molecules corroborated these results; performance for small molecules was comparable between dialyzers. Regarding intradialytic hemocompatibility, FX CorAL showed lower complement, white blood cell, and platelet activation. There were no differences in interdialytic hemocompatibility, PROs, or clinical safety.ConclusionsThe novel FX CorAL with increased membrane hydrophilicity showed strong performance and a favorable hemocompatibility profile as compared to other commonly used dialyzers in clinical practice. Further long-term investigations should examine whether the benefits of FX CorAL will translate into improved cardiovascular and mortality endpoints.Trial registrationeMPORA III registration on 19/01/2021 at ClinicalTrials.gov (NCT04714281).

Early-Stage Protein Adsorption Sequence on Blood-Contacting Surfaces: Answer to Vroman's Question.

Plasma protein adsorption on blood-contacting surfaces is the initiating significant event and modulates the subsequent coagulation response. Despite decades of research in this area, Vroman's questions in 1986 "Who gets there first?" and "When does the next protein arrive?" remain unanswered due to the lack of detection techniques with sufficient temporal resolution. In this work, we develop a droplet microfluidic technology to detect protein adsorption sequences on six typical blood-contacting surfaces in milliseconds. Apolipoproteins (Apo) are found to be the first proteins to adsorb onto the surfaces in a plasma droplet, and the specific type of apolipoprotein depends on the surface. Apo CI is the first protein adsorbed on gold, platinum, graphene, stainless steel, and polyvinyl chloride with the adsorption time varying from 0.01 to 1 s, while Apo CIII preferentially reaches the titanium alloy surface within 1 s. Subsequent to the initial adsorption, Apo AI, AII, and other proteins continue to adsorb until albumin arrives. Thus, the adsorption sequence is revealed, and Vroman's questions are answered. Moreover, this finding demonstrates the influence of the initial protein adsorption on subsequent coagulation at the surface, and it offers new insights into the development of anticoagulant surfaces.

Large-Scale Surface Modification of Decellularized Matrix with Erythrocyte Membrane for Promoting In Situ Regeneration of Heart Valve

In situ regeneration is a promising strategy for constructing tissue engineering heart valves (TEHVs). Currently, the decellularized heart valve (DHV) is extensively employed as a TEHV scaffold. Nevertheless, DHV exhibits limited blood compatibility and notable difficulties in endothelialization, resulting in thrombosis and graft failure. The red blood cell membrane (RBCM) exhibits excellent biocompatibility and prolonged circulation stability and is extensively applied in the camouflage of nanoparticles for drug delivery; however, there is no report on its application for large-scale modification of decellularized extracellular matrix (ECM). For the first time, we utilized a layer-by-layer assembling strategy to immobilize RBCM on the surface of DHV and construct an innovative TEHV scaffold. Our findings demonstrated that the scaffold significantly improved the hemocompatibility of DHV by effectively preventing plasma protein adsorption, activated platelet adhesion, and erythrocyte aggregation, and induced macrophage polarization toward the M2 phenotype in vitro. Moreover, RBCM modification significantly enhanced the mechanical properties and enzymatic stability of DHV. The rat models of subcutaneous embedding and abdominal aorta implantation showed that the scaffold regulated the polarization of macrophages into the anti-inflammatory and pro-modeling M2 phenotype and promoted endothelialization and ECM remodeling in the early stage without thrombosis and calcification. The novel TEHV exhibits excellent performance and can overcome the limitations of commonly used clinical prostheses.

Degradation protection and enhanced biocompatibility of Mg alloys pretreated with plasma proteins.

After implantation of the Mg alloy in the human body, the adsorption of plasma protein on surface will cause a series of cell reactions and affect the degradation of Mg alloys. Herein, in vitro biological reactions of the ZK60 and AZ31 Mg alloys are analyzed in plasma protein environment. Combined with mass spectrometry analysis of the type of adsorbed proteins, it is shown that proteins such as fibrinogen, vitronectin, fibronectin, and prothrombin are prone to get adsorbed on the surface of the alloys than other proteins, leading to the promotion of MG63 cell adhesion and proliferation. The effect of selected proteins (fibrinogen, fibronectin, and prothrombin) on degradation of ZK60 and AZ31 Mg alloys is investigated using immersion tests. The degradation of AZ31 Mg alloy is significantly restrained with the presence of proteins. This is due to the protein adsorption effect on the sample surface. The molecular dynamics simulation results indicate that both fibrinogen and fibronectin tend to adsorb onto the AZ31 rather than ZK60, forming a stable protein layer on the AZ31 Mg alloy retarding the degradation of the samples. As to ZK60 alloy, the addition of protein inhibits the degradation in the short term, however, the degradation increases after a long time of immersion. This phenomenon is particularly pronounced in fibronectin solution.

Ionic liquid-coated lipid nanoparticles increase siRNA uptake into CNS targets.

Lipidoid nanoparticles (LNPs) have transformed the field of drug delivery and are clinically used for the delivery of nucleic acids to liver and muscle targets. Post-intravenous administration, LNPs are naturally directed to the liver due to the adsorption of plasma proteins like apolipoprotein E. In the present work, we have re-engineered LNPs with ionic liquids (ILs) to reduce plasma protein adsorption and potentially increase the accumulation of LNPs in hard-to-deliver central nervous system (CNS) targets such as brain endothelial cells (BECs) and neurons. We have developed two approaches to re-engineer LNPs using a choline trans-2-hexenoate IL: first, we have optimized an IL-coating process using the standard LNP formulation and in the second approach, we have incorporated ILs into the LNPs by replacing the PEG-lipid component in the standard formulation using ILs. IL-coated as well as IL-incorporated LNPs were colloidally stable with morphologies similar to the standard LNPs. IL-coated LNPs showed superior uptake into mouse BECs and neurons and demonstrated reduced mouse plasma protein adsorption compared to the standard LNPs. Overall, our results (1) demonstrate the feasibility of re-engineering the clinically approved LNP platform with highly tunable biomaterials like ILs for the delivery of therapeutics to CNS targets like BECs and neurons and (2) suggest that the surface properties of LNPs play a critical role in altering their affinity to and uptake into hard-to-deliver cell types.

Development of Novel Composite Biocompatible Materials by Surface Modification of Porous Inorganic Compounds Using Bambus[6]Uril

In this present investigation, a novel series of composite materials based on porous inorganic compounds—hydroxyapatite and diatomite—have been innovatively formulated for the first time through surface modification employing the promising macromolecular compound, bambus[6]uril. The process entailed the application of a bambus[6]uril dispersion in water onto the surfaces of hydroxyapatite and diatomite. Extensive characterization was carried out, involving IR spectroscopy and SEM. The materials underwent assessment for hemolytic effects and plasma protein adsorption. The results revealed that materials containing surface-bound bambus[6]uril did not demonstrate inherent hemolytic effects, laying a robust groundwork for their use as biocompatible materials. These findings hold significant promise as an alternative pathway for the development of durable and efficient bio-composites, potentially unveiling supramolecular strategies incorporating encapsulated bambus[6]urils in analogous processes.

Construction of Tumor Microenvironment‐Responsive Gene Carriers

AbstractPeptide‐ and polypeptide‐based self‐assembling gene delivery systems have received considerable attention owing to their inherent biocompatibility and bioactivity. Gene carriers based on elastin‐like polypeptides (ELPs) have been extensively studied because of their controllability and unique temperature responsiveness. The (EK)10‐PLGLAG‐Tat polypeptide sequence was selected for tumor gene delivery, with ELP serving as the hydrophobic core. In this sequence, a hydration layer can be formed on the surface of the carrier using the zwitterionic peptide segment (EK)10, which helps prevent the nonspecific adsorption of plasma proteins. Additionally, the MMP‐2 enzyme‐responsive PLGLAG peptide segment is responsible for exposing the cell‐penetrating peptide Tat specifically near tumor cells, facilitating the penetration of tumor cells. To introduce (EK)10‐PLGLAG‐Tat into the self‐assembling carrier while ensuring its bioactivity, a leucine zipper ZR/ZE with opposite charges was used to link it to the ELP. Because of its high specificity and low systemic toxicity, the carrier was named environmentally responsive gene carrier (ERGV). Experimental results demonstrated that the ERGV effectively removed (EK)10 in MMP‐2 overexpressed environments, altering the surface charge from negative to positive and facilitating ssDNA delivery into tumor cells. These findings highlight the potential of ERGVs as a safe and efficient method for targeted gene delivery to tumors.

Asymmetrical interactions between nanoparticles and proteins arising from deformation upon adsorption to surfaces

Drug release from polymeric nanoparticles (NPs) is governed by their adsorption onto cell membranes and transmigration across cell walls. These steps are influenced by their interactions with proteins near the cells. These interactions were investigated by studying the sequential adsorption of plasma proteins, albumin (Alb) and fibrinogen (Fg), and micellar NPs using quartz crystal microbalance with dissipation (QCMD), X-ray photoelectron spectroscopy (XPS), and small-angle X-ray scattering (SAXS). The three NPs in the study all have poly(ethylene glycol) (PEG) shells but different cores: amorphous poly(propylene oxide) (PPO), crystalline polycaprolactone (PCL), and poly(desaminotyrosyl-tyrosine octyl ester-co-suberic acid) (DTO-SA). None of the NPs adsorbed onto a pre-adsorbed Fg layer. On the other hand, when the deposition sequence was reversed, Fg was adsorbed onto DTO-SA NP and PCL NP surfaces, but not onto the PPO NP surface. The interactions with Alb were different: DTO-SA did not adsorb onto Alb and vice versa; PPO NP adsorbed onto an Alb layer, but Alb did not adsorb onto the PPO NP layer; and PCL NP reversibly adsorbed onto Alb, but Alb displaced pre-adsorbed PCL NP. Thus, in most instances, the adsorption behavior was asymmetric in that it was dependent on the order of arrival of the adsorbates at the substrate. SAXS data did not show evidence for complex formation in solution. Thus, the solution behavior appears not to be a predictor of the interaction of proteins and the NPs near surfaces. Differing strengths of pairwise interactions of proteins, NPs and substrates account for this adsorption behavior. These differences in interactions could be the results of deformation of the adsorbates immobilized at the surface and the different degrees of surface remodeling that occur upon adsorption. Deformation could lead to disassembly of the NPs that has implications on their ability to release their payload of drugs upon adsorption onto tissue surfaces.

Boosting Titanium Surfaces with Positive Charges: Newly Developed Cationic Coating Combines Anticorrosive and Bactericidal Properties for Implant Application.

Along with poor implant-bone integration, peri-implant diseases are the major causes of implant failure. Although such diseases are primarily triggered by biofilm accumulation, a complex inflammatory process in response to corrosive-related metallic ions/debris has also been recognized as a risk factor. In this regard, by boosting the titanium (Ti) surface with silane-based positive charges, cationic coatings have gained increasing attention due to their ability to kill pathogens and may be favorable for corrosion resistance. Nevertheless, the development of a cationic coating that combines such properties in addition to having a favorable topography for implant osseointegration is lacking. Because introducing hydroxyl (-OH) groups to Ti is essential to increase chemical bonds with silane, Ti pretreatment is of utmost importance to achieve such polarization. In this study, plasma electrolytic oxidation (PEO) was investigated as a new route to pretreat Ti with OH groups while providing favorable properties for implant application compared with traditional hydrothermal treatment (HT). To produce bactericidal and corrosion-resistant cationic coatings, after pretreatment with PEO or HT (Step 1), surface silanization was subsequently performed via immersion-based functionalization with 3-aminopropyltriethoxysilane (APTES) (Step 2). In the end, five groups were assessed: untreated Ti (Ti), HT, PEO, HT+APTES, and PEO+APTES. PEO created a porous surface with increased roughness and better mechanical and tribological properties compared with HT and Ti. The introduction of -OH groups by HT and PEO was confirmed by Fourier transform infrared spectroscopy and the increase in wettability producing superhydrophilic surfaces. After silanization, the surfaces were polarized to hydrophobic ones, and an increase in the amine functional group was observed by X-ray photoelectron spectroscopy, demonstrating a considerable amount of positive ions. Such protonation may explain the enhanced corrosion resistance and dead bacteria (Streptococcus aureus and Escherichia coli) found for PEO+APTES. All groups presented noncytotoxic properties with similar blood plasma protein adsorption capacity vs the Ti control. Our findings provide new insights into developing next-generation cationic coatings by suggesting that a tailorable porous and oxide coating produced by PEO has promise in designing enhanced cationic surfaces targeting biomedical and dental implant applications.

Synthesis of magnetic NaY zeolite for plasma proteomics application

Magnetically modified NaY zeolite has shown advantages in high-throughput and large-scale clinical plasma proteomic studies. In this study, magnetic NaY zeolite was prepared via an improved method, "layer by layer adhesion", using epoxy adhesive. The morphology, structure, and magnetic properties of magnetic NaY zeolite were characterized and tested by scanning electron microscope (SEM), fourier transform infrared spectrometer (FT-IR), X-ray diffractometer (XRD), and vibrating sample magnetometer (VSM), and using sodium dodecyl sulfonate-polyacrylamide gelelectrophoresis (SDS-PAGE) and liquid chromatography-tandem mass spectrometry (LC-MS) for plasma proteomics studies. The results showed that NaY zeolite was coated on the surface of Fe3O4 by epoxy adhesive, and such coating did not affect the surface properties of the magnetic zeolite. The saturation magnetization of magnetic NaY zeolite was measured as 9.964 emu g−1. Approximately 2929 proteins could be identified from plasma protein corona formed on magnetic NaY zeolite, reaching 97.6 % of the identification number of pure NaY zeolite. Furthermore, compared with NaY zeolite, the solid-liquid separation processes of magnetic zeolite during plasma proteomics studies were significantly reduced from half an hour to few minutes. Due to excellent plasma protein adsorption performance and rapid magnetic separation property, magnetic NaY zeolite is expected to become a powerful tool for the large-scale adsorption of low-abundant plasma proteins and high-throughput proteomic studies.

Bioactive surface coating for preventing mechanical heart valve thrombosis

BackgroundProsthetic heart valves are the only treatment for most patients with severe valvular heart disease. Mechanical valves, made of metallic components, are the most long-lasting type of replacement valves. However, they are prone to thrombosis and require permanent anticoagulation and monitoring, which leads to higher risk of bleeding and impacts the patient’s quality of life. ObjectivesTo develop a bioactive coating for mechanical valves with the aim to prevent thrombosis and improve patient outcomes. MethodsWe used a catechol-based approach to produce a drug-releasing multilayer coating adherent to mechanical valves. The hemodynamic performance of coated Open Pivot valves was verified in a heart model tester, and coating durability in the long term was assessed in a durability tester producing accelerated cardiac cycles. Coating antithrombotic activity was evaluated in vitro with human plasma or whole blood under static and flow conditions and in vivo after surgical valve implantation in a pig’s thoracic aorta. ResultsWe developed an antithrombotic coating consisting of ticagrelor- and minocycline-releasing cross-linked nanogels covalently linked to polyethylene glycol. We demonstrated the hydrodynamic performance, durability, and hemocompatibility of coated valves. The coating did not increase the contact phase activation of coagulation, and it prevented plasma protein adsorption, platelet adhesion, and thrombus formation. Implantation of coated valves in nonanticoagulated pigs for 1 month efficiently reduced valve thrombosis compared with noncoated valves. ConclusionOur coating efficiently inhibited mechanical valve thrombosis, which might solve the issues of anticoagulant use in patients and the number of revision surgeries due to valve thrombosis despite anticoagulation.