Study of Hydration Repulsion of Zwitterionic Polymer Brushes Resistant to Protein Adhesion through Molecular Simulations.

The fabrication of antifouling zwitterionic polymer brushes represents a leading approach to mitigate nonspecific adhesion on the surfaces of medical devices. This investigation seeks to elucidate the correlation between the material composition and structural attributes of these polymer brushes in preventing protein adhesion. To achieve this goal, we modeled three different zwitterionic brushes, namely, carboxybetaine methacrylate (CBMA), sulfobetaine methacrylate (SBMA), and (2-(methacryloyloxy)ethyl)-phosphorylcholine (MPC). The simulations revealed that elevating the grafting density enhances the structural stability, hydration strength, and resistance to protein adhesion exhibited by the polymer brushes. PCBMA manifests a more robust hydration layer, while PMPC demonstrates the slightest interaction with proteins. In a comprehensive evaluation, PSBMA polymer brushes emerged as the best choice with superior stability, enhanced protein repulsion, and minimally induced protein deformation, resulting in effective resistance to nonspecific adhesion. The high-density SBMA polymer brushes significantly reduce the level of protein adhesion in AFM testing. In addition, we have pioneered the quantitative characterization of hydration repulsion in polymer brushes by analyzing the hydration repulsion characteristics at different materials and graft densities. In summary, our study provides a nuanced understanding of the material and structural determinants influencing the capacity of zwitterionic polymer brushes to thwart protein adhesion. Additionally, it presents a quantitative elucidation of hydration repulsion, contributing to the advancement and application of antifouling polymer brushes.

High-density zwitterionic polymer brushes exhibit robust lubrication properties and high antithrombotic efficacy in blood-contacting medical devices.

High-performance catheters are essential for interventional surgeries, requiring reliable anti-adhesive and lubricated surfaces. This article develops a strategy for constructing high-density sulfobetaine zwitterionic polymer brushes on the surface of catheters, utilizing dopamine and sodium alginate as the primary intermediate layers, where dopamine provides mussel-protein-like adhesion to anchor the polymer brushes to the catheter surface. Hydroxyl-rich sodium alginate increases the number of grafting sites and improves the grafting mass by more than 4 times. The developed high-density zwitterionic polymer brushes achieve long-lasting and effective lubricity (µ<0.0078) and are implanted in rabbits for four hours without bio-adhesion and thrombosis in the absence of anticoagulants such as heparin. Experiments and molecular dynamics simulations demonstrate that graft mass plays a decisive role in the lubricity and anti-adhesion of polymer brushes, and it is proposed to predict the anti-adhesion of polymer brushes by their lubricity to avoid costly and time-consuming bioassays during the development of amphoteric polymer brushes. A quantitative influence of hydration in the anti-adhesion properties of amphiphilic polymer brushes is also revealed. Thus, this study provides a new approach to safe, long-lasting lubrication and anticoagulant surface modification for medical devices in contact with blood. STATEMENT OF SIGNIFICANCE: High friction and bioadhesion on medical device surfaces can pose a significant risk to patients. In response, we have developed a safer, simpler, and more application-specific surface modification strategy that addresses both the lubrication and anti-bioadhesion needs of medical device surfaces. We used dopamine and sodium alginate as intermediate layers to drastically increase the grafting density of the zwitterionic brushes and enabled the modified surfaces to have an extremely low coefficient of friction (µ = 0.0078) and to remain non-bioadhesive for 4 hours in vivo. Furthermore, we used molecular dynamics simulations to gain insight into the mechanisms behind the superior anti-adhesion properties of the high-density polymer brushes. Our work contributes to the development and application of surface-modified coatings.

Surface modification of polyvinyl chloride with sodium alginate/carboxymethyl chitosan and heparin for realizing the anticoagulation.

Thrombosis of extracorporeal circuits causes significant morbidity and mortality worldwide. In this study, plasma treatment technology and chemical grafting method were used to construct heparinized surfaces on the PVC substrate, which could not only reduce thrombosis but also decrease the side effects of the direct injection of anticoagulants. The PVC substrate was modified by plasma treatment technology firstly to obtain the active surface with the hydroxyl groups used for grafting. Then, heparin was grafted onto the modified PVC surface using different grafting strategies to prepare different heparinized surfaces. The experimental results indicated that the sodium alginate (SA) and carboxymethyl chitosan (CCS) used as interlayers could significantly increase the graft density of heparin to improve the anticoagulant effects and hemocompatibility of heparinized surfaces. In addition, the modification of heparin can further improve the anticoagulant effects. The CCS/low-molecular-weight heparin (LWMH) surface has the best anticoagulant properties, which can prolong the activated partial thromboplastin time (APTT) values of human plasma for about 35 s, reduce the hemolysis rates to <0.3 %, and perform well in the in-vitro blood circulation test. The heparinized surfaces prepared in this work have great application potential in anticoagulant treatment for medical devices.

Design, preparation, and characterization of lubricating polymer brushes for biomedical applications.

The lubrication modification of biomedical devices significantly enhances the functionality of implanted interventional medical devices, thereby providing additional benefits for patients. Polymer brush coating provides a convenient and efficient method for surface modification while ensuring the preservation of the substrate's original properties. The current research has focused on a "trial and error" method to finding polymer brushes with superior lubricity qualities, which is time-consuming and expensive, as obtaining effective and long-lasting lubricity properties for polymer brushes is difficult. This review summarizes recent research advances in the biomedical field in the design, material selection, preparation, and characterization of lubricating and antifouling polymer brushes, which follow the polymer brush development process. This review begins by examining various approaches to polymer brush design, including molecular dynamics simulation and machine learning, from the fundamentals of polymer brush lubrication. Recent advancements in polymer brush design are then synthesized and potential avenues for future research are explored. Emphasis is placed on the burgeoning field of zwitterionic polymer brushes, and highlighting the broad prospects of supramolecular polymer brushes based on host-guest interactions in the field of self-repairing polymer brush applications. The review culminates by providing a summary of methodologies for characterizing the structural and functional attributes of polymer brushes. It is believed that a development approach for polymer brushes based on "design-material selection-preparation-characterization" can be created, easing the challenge of creating polymer brushes with high-performance lubricating qualities and enabling the on-demand creation of coatings. STATEMENT OF SIGNIFICANCE: Biomedical devices have severe lubrication modification needs, and surface lubrication modification by polymer brush coating is currently the most promising means. However, the design and preparation of polymer brushes often involves "iterative testing" to find polymer brushes with excellent lubrication properties, which is both time-consuming and expensive. This review proposes a polymer brush development process based on the "design-material selection-preparation-characterization" strategy and summarizes recent research advances and trends in the design, material selection, preparation, and characterization of polymer brushes. This review will help polymer brush researchers by alleviating the challenges of creating polymer brushes with high-performance lubricity and promises to enable the on-demand construction of polymer brush lubrication coatings.

Construction of the Mussel-Inspired PDAM/Lysine/Heparin Composite Coating Combining Multiple Anticoagulant Strategies.

The thrombosis of the extracorporeal circuits leads to serious complications, which affect the life safety of the patients significantly. However, intravenous anticoagulants such as heparin may induce bleeding, hypersensitivity, and other adverse reactions. In this study, the mussel-inspired composite coating consisting of polydopamine (PDAM), lysine, and modified heparin was constructed on the commonly used medical poly(vinyl chloride) (PVC) tubes to reduce thrombosis by combining the immobilization of anticoagulants and the construction of bioinert surface strategies. First, the PDAM/lysine coating rich in amine groups was constructed in a mixed solution of dopamine and lysine through the co-deposition reaction. Then, the modified heparin was covalently immobilized on the PDAM/lysine coating to obtain composite coating. Finally, the graft density and stability of heparin and anticoagulant properties of the composite coating were tested. The results showed that the composite coating could inhibit the adhesion and activation of platelets significantly and prolong the activated partial thromboplastin time (APTT) remarkably for over 25 s. The composite coating also had excellent hemocompatibility, and the hemolysis ratio was less than 0.5%. Particularly, the anticoagulant coating performed well in the in vitro blood circulation test. The composite coating constructed in this work show great potential in the anticoagulant treatment for medical devices.