Thanks to its simplicity, versatility, and secondary reactivity, dopamine self-polymerized coatings (pDA) have been widely used in surface modification of biomaterials, but the limitation in secondary molecular grafting and the high roughness restrain their application in some special scenarios. Therefore, some other catecholamine coatings analog to pDA have attracted more and more attention, including the smoother poly-norepinephrine coating (pNE), and the poly-levodopa coating (pLD) containing additional carboxyl groups. However, the lack of a systematic comparison of the properties, especially the biological properties of the above three catecholamine coatings, makes it difficult to give a guiding opinion on the application scenarios of different coatings. Herein, we systematically studied the physical, chemical, and biological properties of the three catecholamine coatings, and explored the feasibility of their application for the modification of biomaterials, especially cardiovascular materials. Among them, the pDA coating was the roughest, with the largest amount of amino and phenolic hydroxyl groups for molecule grafting, and induced the strongest platelet adhesion and activation. The pLD coating was the thinnest and most hydrophilic but triggered the strongest inflammatory response. The pNE coating was the smoothest, with the best hemocompatibility and histocompatibility, and with the strongest cell selectivity of promoting the proliferation of endothelial cells while inhibiting the proliferation of smooth muscle cells. To sum up, the pNE coating may be a better choice for the surface modification of cardiovascular materials, especially those for vascular stents and grafts, but it is still not widely recognized.

Thrombosis associated with implants can severely impact therapeutic outcomes and lead to increased morbidity and mortality. Thus, developing blood-contacting materials with superior anticoagulant properties is essential to prevent and mitigate device-related thrombosis. Herein, we propose a novel single-molecule multi-functional strategy for creating blood-compatible surfaces. The synthesized azide-modified Cu-DOTA-(Lys)₃ molecule, which possesses both NO release and fibrinolysis functions, was immobilized on material surfaces via click chemistry. Due to the specificity, rapidity, and completeness of click chemistry, the firmly grafted Cu-DOTA-(Lys)₃ endows the modified material with excellent antithrombotic properties of vascular endothelium and thrombolytic properties of fibrinolytic system. This surface effectively prevented thrombus formation in both in vitro and in vivo experiments, owing to the synergistic effect of anticoagulation and thrombolysis. Moreover, the modified material maintained its functional efficacy after one month of PBS immersion, demonstrating excellent stability. Overall, this single-molecule multifunctional strategy may become a promising surface engineering technique for blood-contacting materials.

BACKGROUND: Vascular calcification is an active process driven by osteogenic phenotypic transition of vascular smooth muscle cells (VSMCs) and regulated by a bone-related gene regulatory network. Recent studies showed that FAK (focal adhesion kinase) regulates bone formation by affecting the cellular localization of HDAC (histone deacetylase) 4 and HDAC5. However, it is not known whether FAK exerts effects on vascular calcification in VSMCs through regulating HDACs. METHODS: We used perturbational assays to assess the role of HDAC4, HDAC5, and FAK in VSMC calcification. Pharmacological inhibition and gene silencing of FAK were used to evaluate effects on calcification, cell migration, and the expression of procalcification factors. Leptomycin was used to inhibit the nuclear export of HDACs. In addition, ex vivo cultures of mouse and human arteries were treated with a FAK inhibitor to assess effects on arterial calcification. Single-cell transcriptomic expression of FAK was examined in healthy and diseased human coronary arteries. RESULTS: HDAC4 and HDAC5 were identified as positive regulators of vascular calcification. Pharmacological inhibition or gene silencing of FAK blocked VSMC calcification, abrogated the osteogenic medium–induced elevation of procalcification factors, and reduced cell migration. FAK inhibition reduced HDAC4 and HDAC5 phosphorylation and enhanced nuclear localization of these HDAC proteins. Inhibition of HDAC4 and HDAC5 nuclear export with leptomycin showed similar effects on calcification as FAK inhibition. Treatment with the FAK inhibitor attenuated the calcification of ex vivo mouse and human arteries. FAK gene expression was dysregulated in human diseased coronary arteries compared with healthy coronary arteries, and, in single-cell analysis of human arterial tissue, FAK expression was highest in VSMCs at an intermediate state between contractile and osteogenic phenotypes. CONCLUSIONS: FAK promotes VSMC calcification, at least in part, via phosphorylation of HDAC4 and HDAC5. Targeted regulation of the activity of FAK, HDAC4, and HDAC5 may be an effective strategy for the treatment of vascular calcification.

Tirofiban is a glycoprotein IIb/IIIa receptor blocker mainly used alongside other blood thinners in patients with acute coronary syndrome (ACS) undergoing procedures like angioplasty (PCI). Emerging clinical evidence suggests it may also be beneficial during endovascular treatment for ischemic stroke (IS). Because Tirofiban prevents blood clotting, it is important to assess how often it causes serious bleeding or other side effects when used in real-life settings. We used disproportionality analysis to review all FDA-reported adverse events linked to Tirofiban (from 2004 onward), focusing on cases where the drug was the primary suspect. The study results confirmed known AEs such as bleeding and thrombocytopenia. We observed both commonly reported bleeding events (e.g., brain and gut bleeding) and less commonly recognized types, such as hemothorax and hemorrhagic shock. Furthermore, other relatively rare but statistically significant AEs were identified, including acute respiratory failure, hemolysis, prolonged activated partial thromboplastin time (APTT), coagulopathy, and disseminated intravascular coagulation (DIC). The temporal analysis showed the median onset time of AEs was 1 day, which urges immediate monitoring after drug administration, such as symptom surveillance and complete blood count evaluation.