A multi-in-one strategy with glucose-triggered long-term antithrombogenicity and sequentially enhanced endothelialization for biological valve leaflets.

Bioprosthetic heart valves are commonly applied in heart valve replacement, while the effectiveness is limited by inflammation, calcification and especially thrombosis. Surface modification is expected to endow the biological valves with versatility. Herein, a multi-in-one strategy was established to modify biological valves with long-term antithrombogenicity and sequentially enhanced endothelialization triggered by glucose, in which the direct thrombin inhibitor rivaroxaban (RIVA)-loaded nanogels were embedded and the detachable polyethylene glycol (PEG) was grafted. These two anticoagulant strategies were connected by glucose oxidase (GOx), which catalyzed the oxidation of glucose to produce hydrogen peroxide (H2O2) and local acidic environment. The generated H2O2 stimulated H2O2-responsive nanogels release RIVA to obtain continuous antithrombogenicity. Meanwhile, PEG was attached to the surface via pH-sensitive bonds, which prevented thrombus formation by resisting the serum proteins and platelets adhesion at the initial stage of material/blood contact. Sequentially, PEG gradually peeled off under the local weak acidic environment, which ultimately resulted in the endothelialization enhancement. Within such multi-in-one strategy, the biological valve leaflets induced long-term anticoagulant performance, gradually enhanced endothelialization and improved tissue affinity, including anti-calcification and anti-inflammation, indicating the potential of the response sequence matching between materials and tissues after implantation, which might improve performance of biological heart valves.

Dressing Blood-Contacting Materials by a Stable Hydrogel Coating with Embedded Antimicrobial Peptides for Robust Antibacterial and Antithrombus Properties.

Although dressing blood-contacting devices with robust and synergistic antibacterial and antithrombus properties has been explored for several decades, it still remains a great challenge. In order to endow materials with remarkable antibacterial and antithrombus abilities, a stable and antifouling hydrogel coating was developed via surface-initiated polymerization of sulfobetaine methacrylate and acrylic acid on a polymeric substrate followed by embedding of antimicrobial peptides (AMPs), including WR (sequence: WRWRWR-NH2) or Bac2A (sequence: RLARIVVIRVAR-NH2) AMPs. The chemical composition of the AMP-embedded hydrogel coating was determined through XPS, zeta potential, and SEM-EDS measurements. The AMP-embedded antifouling hydrogel coating showed not only good hemocompatibility but also excellent bactericidal and antiadhesion properties against Gram-positive and Gram-negative bacteria. Moreover, the hydrogel coating could protect the AMPs with long-term bioactivity and cover the positive charge of the dotted distributed AMPs, which in turn well retained the hemocompatibility and antifouling capacity of the bulk hydrogels. Furthermore, the microbiological results of animal experiments also verified the anti-infection performance in vivo. Histological and immunological data further indicated that the hydrogel coating had an excellent anti-inflammatory function. Therefore, the present study might provide a promising approach to prevent bacterial infections and thrombosis in clinical applications of blood-contacting devices and related implants.

Epigallocatechin gallate mediated sandwich-like coating for mimicking endothelium with sustained therapeutic nitric oxide generation and heparin release.

In-stent restenosis after stenting is generally characterized by an inflammatory response, excessive proliferation of smooth muscle cells, and delayed healing of the endothelium layer. In this study, inspired by catechol/gallol surface chemistry, a sandwich-like layer-by-layer (LBL) coating was developed using chitosan and heparin as polyelectrolytes, along with the embedding of an epigallocatechin gallate/copper (EGCG/Cu) complex. The embedding of EGCG stabilized the coating by various intermolecular interactions in the LBL coating (e.g., π-π stacking, weak intermolecular crosslinking, and enriched hydrogen bonding) and supported the sustained release of the cargo heparin over 90 days. This design enabled a biomimetic endothelium function in terms of the sustained release of heparin and continuous in situ generation of nitric oxide, driven by the catalytic decomposition of endogenous S-nitrostothiols by copper ions. The result showed enhanced durability of anticoagulation and suppressed inflammatory response. Moreover, the "sandwich-like" coating supported the growth of endothelial cells and up-regulated the protein expression of vascular endothelial growth factor, while effectively suppressing the proliferation and migration of smooth muscle cells (SMCs) via the up-regulation of cyclic guanosine monophosphate. Ex vivo and in vivo experiments demonstrated the effectiveness of the sandwich-like coating in preventing thrombosis formation, suppressing the growth of SMCs, reducing the infiltration and activation of inflammatory cells, and ultimately achieving rapid in situ endothelialization. Hence, the EGCG-assisted sandwich-like coating might be used as a robust and versatile surface modification strategy for implantable cardiovascular devices.

A conformally adapted all-in-one hydrogel coating: towards robust hemocompatibility and bactericidal activity.

Hospital-acquired infections and thrombosis caused by bacteria attached to the device surface, or fibrin crosslinking owing to platelet accumulation/activation, are major healthcare challenges that cause morbidity and mortality. To prevent these, surface coating technologies are considered an efficient tool that can combine hemocompatibility and bactericidal activity. In this study, surface-initiated polymerization was conducted to form an all-in-one hydrogel coating that could adapt to diverse medical devices. Different monomer ratios (acrylamide/acrylic acid) were used to adjust the antimicrobial agent loading capacity. The hydrogel coating obtained by a simple dip-absorbing method showed good hemocompatibility and maintained efficient bactericidal activity. We also explored the loading and release of antimicrobial agents with different molecular sizes, including nano-Ag particles, antibiotics, and antimicrobial peptides. The inhibition zone test and confocal laser scanning microscopy revealed that the hydrogel coating could maintain remarkable antimicrobial and antifouling properties for four weeks. Furthermore, the hydrogel coating decreased the platelet adhesion/activation without risk of hemolysis. The ex vivo blood circulation study confirmed the antithrombotic properties of the hydrogel coating. Such all-in-one hydrogel coatings that maintain high cell viability and exhibit both hemocompatibility and bactericidal activity possess the potential for applications in blood-contacting devices.

A clinical assessment of the Glidescope videolaryngoscope in nasotracheal intubation with general anesthesia.

STUDY OBJECTIVES: To evaluate the efficacy and safety of the Glidescope videolaryngoscope as a device to aid nasotracheal intubation, and to determine whether the GSVL provides a better laryngeal view in patients with difficult laryngoscopy compared with the Macintosh laryngoscope. DESIGN: Prospective, clinical study. SETTING: Two university hospitals. PATIENTS: 156 healthy adult ASA physical status I and II undergoing elective plastic and intraoral surgery with general anesthesia. INTERVENTIONS: After anesthesia induction with intravenous injection of fentanyl 2 microg/kg, propofol 2 mg/kg, and vecuronium 0.1 mg/kg, nasotracheal intubation was performed using GSVL. MEASUREMENTS: Preoperative airway measurements were taken to predict potential difficult airways. During nasotracheal intubation using GSVL, laryngeal views, times required for full visualization of glottis and successful intubation, difficulty encountered and auxiliary maneuvers adopted, and upper airway trauma were recorded. The laryngeal views obtained by GSVL and by Macintosh laryngoscope were compared. MAIN RESULTS: The laryngeal views obtained by GSVL in all patients were Cormack and Lehane (C&L) grades I and II, and the success rate of intubation using GSVL at one attempt was 98.1%. The times required for visualization of the glottis and successful intubation were 40.2 +/- 11.5 s and 52.7 +/- 12.3 seconds, respectively. Patients with C&L grade II needed more auxiliary maneuvers to achieve successful intubation than did those with C&L grade I (P < 0.001). In 36 patients with potential difficult airways, the frequency of difficult laryngoscopy (C&L grades III and IV) with the Macintosh laryngoscope (58.3%) was significantly higher than with the GSVL (0%, P < 0.05). The frequency of minor upper airway trauma was 4.5%. CONCLUSIONS: The GSVL is an effective device for nasotracheal intubation and may be incorporated easily into routine clinical practice. Compared with the Macintosh laryngoscope, the GSVL can provide an improved laryngeal view in the patient with difficult airway.