Hemocompatibility Multi-in-One Hydrogel Coating with ROS-Triggered Inflammation Suppression and Anti-Infection Properties for Blood-Contacting Device.

In traditional blood-contacting medical devices, infection and thrombosis are easily formed on the surface of the materials. In addition, inflammation is also a clinical complication that cannot be ignored. More importantly, there is a mutually promoting relationship between the inflammatory response and the infection as well as thrombosis. In this work, we propose a self-adaptive anti-inflammatory coating strategy combined with anti-infection and anticoagulant capacity, which was accomplished based on nano-Ag particles and dexamethasone (Dex)-loaded hydrogel coating. The coating loaded with nano-Ag endows it with good bactericidal performance, including Gram-positive and Gram-negative bacteria. As an anti-inflammatory drug, Dex was grafted onto hydrogel coating by a reactive oxygen species (ROS)-cleavable thioketal (TK) bond and released upon the trigger of an inflammatory environment, blocking further inflammatory cascade, providing self-adaptive anti-inflammatory properties, and avoiding side effects of the drug. It was demonstrated that the coating worked as a precise strategy to resist coagulation, infection, and inflammation, provided a new perspective for designing clinical complication-conformable coatings, and had great application prospects on blood-contacting medical devices.

Polyvinylpyrrolidone hydrogel coating for ureteral stent: Safety and performance evaluation.

BACKGROUND: Ureteral stents are commonly used in urology. However, complications such as encrustation and infection on the surface of the stent, and injury to the ureteral mucosa can occur after implantation, causing discomfort for patients. OBJECTIVE: We intend to confirm the biosafety of polyvinylpyrrolidone (PVP) hydrophilic coating and its lubrication properties for surface modification of ureteral stents to reduce friction and improve patient comfort. METHODS: Based on our previous studies, we have developed a PVP hydrophilic coating for surface modification of ureteral stents. We firstly investigated the cytotoxicity, intradermal irritation, delayed type hypersensitivity, and acute systemic reactions of stent coating extracts. We further characterized the break strength, retention strength, and dynamic friction of the stent. RESULTS: The cell survival rate of all experimental groups was greater than 70%. No hypersensitivity reaction, systemic toxicity reaction, or obvious intradermal reaction were observed. The above results indicate that the test results of the modified stent meet the requirements of ISO 10993-5: 2009 (Cytotoxicity); ISO 10993-10:2021 (Sensitization and Irritation); ISO 10993-11:2017 (Acute Systemic Toxicity). After soaking in artificial urine for an extended period, there was no obvious change in its super-slip performance. CONCLUSION: Our results confirm the safety and lubrication characteristics of PVP hydrophilic coating for ureteral stent surface modification. The performance of this coating has the potential to reduce complications after stent implantation, thereby improving patient comfort, reducing medical burden, and has a good clinical application prospect.

Surface Engineering of Central Venous Catheters via Combination of Antibacterial Endothelium-Mimicking Function and Fibrinolytic Activity for Combating Blood Stream Infection and Thrombosis.

Long-term blood-contacting devices (e.g., central venous catheters, CVCs) still face the highest incidence of blood stream infection and thrombosis in clinical application. To effectively address these complications, this work reports a dual-functional surface engineering strategy for CVCs by organic integration of endothelium-mimicking and fibrinolytic functions. In this proposal, a lysine (Lys)/Cu2+ -incorporated zwitterionic polymer coating (defined as PDA/Lys/Cu-SB) is designed and robustly fabricated onto commercial CVCs using a facile two-step process. Initially, adhesive ene-functionalized dopamine is covalently reacted with Lys and simultaneously coordinated with bactericidal Cu2+ ions, leading to the deposition of a PDA/Lys/Cu coating on CVCs through mussel foot protein inspired surface chemistry. Next, zwitterionic poly(sulfobetaine methacrylate) (pSB) brushes are grafted onto the PDA/Lys/Cu coating to endow lubricant and antifouling properties. In the final PDA/Lys/Cu-SB coating, endothelium-mimicking function is achieved by combining the catalytic generation of nitric oxide from the chelated Cu2+ with antifouling pSB brushes, which led to significant prevention of thrombosis, and bacterial infection in vivo. Furthermore, the immobilized Lys with fibrinolytic activity show remarkably enhanced long-term anti-thrombogenic properties as evidenced in vivo by demonstrating the capability to lyse nascent clots. Therefore, this developed strategy provides a promising solution for long-term blood-contacting devices to combat thrombosis and infection.

Recent advance in treatment of atherosclerosis: Key targets and plaque-positioned delivery strategies.

Atherosclerosis, a chronic inflammatory disease of vascular wall, is a progressive pathophysiological process with lipids oxidation/depositing initiation and innate/adaptive immune responses. The coordination of multi systems covering oxidative stress, dysfunctional endothelium, diseased lipid uptake, cell apoptosis, thrombotic and pro-inflammatory responding as well as switched SMCs contributes to plaque growth. In this circumstance, inevitably, targeting these processes is considered to be effective for treating atherosclerosis. Arriving, retention and working of payload candidates mediated by targets in lesion direct ultimate therapeutic outcomes. Accumulating a series of scientific studies and clinical practice in the past decades, lesion homing delivery strategies including stent/balloon/nanoparticle-based transportation worked as the potent promotor to ensure a therapeutic effect. The objective of this review is to achieve a very brief summary about the effective therapeutic methods cooperating specifical targets and positioning-delivery strategies in atherosclerosis for better outcomes.

Stearic acid modified nano CuMOFs used as a nitric oxide carrier for prolonged nitric oxide release.

Nitric oxide (NO) shows high potential in the cardiovascular system with anticoagulant and antibacterial efficacy. Cu based metal organic frameworks with amino modification (CuMOFs) were found to have an extraordinary high NO loading, but at the expense of framework stability in ambient moisture. Nano CuMOFs was synthesized by hydrothermal method in this work, and treated with stearic acid (SA) creating a hydrophobic form. It was found that the structure of the particles was not affected after treatment with SA, and the treated CuMOFs had tunable hydrophobicity. Both CuMOFs and SA modified CuMOFs adsorbed NO with the reaction of the amino group and NO to form a NONOate. SA modification enhanced stability of the CuMOFs in phosphate buffer solution (PBS, pH = 7.4), slowed down the interaction between the NO loading unit and H2O, and thus NO releasing was prolonged. The resulting NO-loaded CuMOFs inhibited platelet activation dramatically, prolonged the coagulation time and displayed excellent antibacterial properties. They could be envisioned as a good candidate for application in blood contacting implants.

NO released via both a Cu-MOF-based donor and surface-catalyzed generation enhances anticoagulation and antibacterial surface effects.

The anticoagulation and antibacterial functions of implant and interventional catheters during indwelling will determine their success or failure. Here, an amino-containing copper-based metal-organic framework (Cu-MOF) coating was prepared on the thermoplastic polyurethane substrate (TPU) surface by spin coating for anti-thrombotic and anti-infection effects. The adhesion properties of the polyurethane prepolymer coating (PC) enhanced the binding force of Cu-MOF particles and TPU surface and improved stability. Due to the coordination affinity of Cu2+ with nitric oxide (NO) and the NO loading capacity of the amino group, it showed that a large amount of NO was loaded in the coating. Meanwhile, the coordinated Cu2+ in the coating also catalyzed endogenous NO donors to generate NO, which prolonged the NO release for up to 30 days. The results of antibacterial experiments showed that the NO released from the coating had good antibacterial effects on both E. coli and S. epidermidis. An obvious antibacterial ring can be seen and the antibacterial rate was higher than 96%. It also showed inhibiting platelet adhesion and activation, prolonged in vitro clotting time and inhibited thrombus formation. In summary, for the first time, NO release from the coating was realized by the combined ways of NO donor and catalytic endogenous NO donor. It can not only meet the high NO release rate required for early anticoagulation and antibacterial of the catheter but also maintain normal anticoagulation requirements in the later period.

A Uniform and Robust Bioinspired Zwitterion Coating for Use in Blood-Contacting Catheters with Improved Anti-Inflammatory and Antithrombotic Properties.

Inflammation and thrombosis are two major complications of blood-contacting catheters that are used as extracorporeal circuits for hemodialysis and life-support systems. In clinical applications, complications can lead to increased mortality and morbidity rates. In this work, a biomimetic erythrocyte membrane zwitterion coating based on poly(2-methacryloyloxyethyl phosphorylcholine-co-dopamine methacrylate) (pMPCDA) copolymers is uniformly and robustly modified onto a polyvinyl chloride (PVC) catheter via mussel-inspired surface chemistry. The zwitterionic pMPCDA coating exhibits excellent antifouling activity and resists bacterial adhesion, fibrinogen adsorption, and platelet adhesion/activation. The material also demonstrates great hemocompatibility, cytocompatibility, and anticoagulation properties in vitro. Additionally, this biocompatible pMPCDA coating reduces in vivo foreign-body reactions by mitigating inflammatory response and collagen capsule formation, due to its outstanding ability to resist nonspecific protein adsorption. More importantly, when compared with a bare PVC catheter, the pMPCDA coating exhibits outstanding antithrombotic properties when tested in an ex vivo rabbit perfusion model. Thus, it is envisioned that this biomimetic erythrocyte membrane surface strategy will provide a promising way to mitigate inflammation and thrombosis caused by the use of blood-contacting catheters.