Yue Siyuan, Zhang Wentai, Ma Qing, Zhang Zhen, Lu Jing, Yang Zhilu
School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Dongguan Key Laboratory of Smart Biomaterials and Regenerative Medicine, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, 523059, China.
Bioact Mater. 2024 Sep 9;42:366-378. doi: 10.1016/j.bioactmat.2024.09.009. eCollection 2024 Dec.
Thrombosis and infection are pivotal clinical complications associated with interventional blood-contacting devices, leading to significant morbidity and mortality. To address these issues, we present a stepwise metal-catechol-(amine) (MCA) surface engineering strategy that efficiently integrates therapeutic nitric oxide (NO) gas and antibacterial peptide (ABP) onto catheters, ensuring balanced anti-thrombotic and anti-infective properties. First, copper ions were controllably incorporated with norepinephrine and hexanediamine through a one-step molecular/ion co-assembly process, creating a NO-generating and amine-rich MCA surface coating. Subsequently, azide-polyethylene glycol 4-N-hydroxysuccinimidyl and dibenzylcyclooctyne modified ABP were sequentially immobilized on the surface via amide coupling and bioorthogonal click chemistry, ensuring the dense grafting of ABP while maintaining the catalytic efficacy for NO. This efficient integration of ABP and NO-generating ability on the catheter surface provides potent antibacterial properties and ability to resist adhesion and activation of platelets, thus synergistically preventing infection and thrombosis. We anticipate that this synergistic modification strategy will offer an effective solution for advancing surface engineering and enhancing the clinical performance of biomedical devices.
血栓形成和感染是与介入性血液接触装置相关的关键临床并发症,会导致显著的发病率和死亡率。为了解决这些问题,我们提出了一种逐步的金属-儿茶酚-(胺)(MCA)表面工程策略,该策略可将治疗性一氧化氮(NO)气体和抗菌肽(ABP)有效地整合到导管上,确保抗血栓和抗感染性能的平衡。首先,通过一步分子/离子共组装过程将铜离子与去甲肾上腺素和己二胺可控地结合,形成产生NO且富含胺的MCA表面涂层。随后,通过酰胺偶联和生物正交点击化学将叠氮基聚乙二醇4-N-羟基琥珀酰亚胺和二苄基环辛炔修饰的ABP依次固定在表面,确保ABP的密集接枝,同时保持对NO的催化功效。ABP与导管表面产生NO能力的这种有效整合提供了强大的抗菌性能以及抵抗血小板粘附和活化的能力,从而协同预防感染和血栓形成。我们预计这种协同修饰策略将为推进表面工程和提高生物医学装置的临床性能提供有效的解决方案。