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基于生物启发的壳聚糖对生物医学植入物表面进行功能化以增强血液相容性、抗氧化和抗凝潜力:一项体外和体内研究。

Bioinspired chitosan based functionalization of biomedical implant surfaces for enhanced hemocompatibility, antioxidation and anticoagulation potential: an and study.

作者信息

Hassan Sadia, Bilal Namra, Khan Tooba Javaid, Ali Murtaza Najabat, Ghafoor Bakhtawar, Saif Khawaja Usman

机构信息

School of Mechanical and Manufacturing Engineering (SMME), National University of Sciences and Technology Islamabad Pakistan

Nencki Institute of Experimental Biology Poland.

出版信息

RSC Adv. 2024 Jul 1;14(29):20691-20713. doi: 10.1039/d4ra00796d. eCollection 2024 Jun 27.

Abstract

Endowing implanted biomaterials with better hemocompatibility, anticoagulation, antioxidant and antiplatelet adhesion is necessary because of their potential to trigger activation of multiple reactive mechanisms including coagulation cascade and potentially causing serious adverse clinical events like late thrombosis. Active ingredients from natural sources including , , and have the ability to inhibit the coagulation cascade and thrombus formation around biomedical implants. These properties are of interest for the development of a novel drug for biomedical implants to potentially solve the current blood clotting and coagulation problems which lead to stent thrombosis. The objective of this study was to incorporate different anticoagulants from natural sources into a degradable matrix of chitosan with varying concentrations ranging from 5% to 15% and a composite containing all three drugs. The presence of anticoagulant constituents was identified using GC-MS. Subsequently, all the compositions were characterized principally by using Fourier transform infrared spectroscopy and scanning electron microscopy while the drug release profile was determined using UV-spectrometry for a 30 days immersion period. The results indicated an initial burst release which was subsequently followed by the sustained release pattern. Compared to heparin loaded chitosan, DPPH and hemolysis tests revealed better blood compatibility of natural drug loaded films. Moreover, the anticoagulation activity of natural drugs was equivalent to the heparin loaded film; however, through docking, the mechanism of inhibition of the coagulation cascade of the novel drug was found to be through blocking the extrinsic pathway. The study suggested that the proposed drug composite expresses an optimum composition which may be a practicable and appropriate candidate for biomedical implant coatings.

摘要

赋予植入生物材料更好的血液相容性、抗凝性、抗氧化性和抗血小板粘附性是必要的,因为它们有可能触发包括凝血级联反应在内的多种反应机制的激活,并可能导致严重的不良临床事件,如晚期血栓形成。来自天然来源的活性成分,包括[具体成分1]、[具体成分2]和[具体成分3],具有抑制生物医学植入物周围凝血级联反应和血栓形成的能力。这些特性对于开发一种新型生物医学植入物药物以潜在解决当前导致支架血栓形成的血液凝固问题具有重要意义。本研究的目的是将不同的天然来源抗凝剂掺入浓度范围为5%至15%的可降解壳聚糖基质中,并制成包含所有三种药物的复合材料。使用气相色谱 - 质谱法鉴定抗凝成分的存在。随后,主要通过傅里叶变换红外光谱和扫描电子显微镜对所有组合物进行表征,同时使用紫外光谱法测定30天浸泡期内的药物释放曲线。结果表明最初有一个突发释放,随后是持续释放模式。与负载肝素的壳聚糖相比,二苯基苦味酰基自由基(DPPH)和溶血试验表明负载天然药物的薄膜具有更好的血液相容性。此外,天然药物的抗凝活性与负载肝素的薄膜相当;然而,通过对接发现,新型药物抑制凝血级联反应的机制是通过阻断外源性途径。该研究表明,所提出的药物复合材料表现出一种最佳组成,可能是生物医学植入物涂层的一种可行且合适的候选材料。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fc1/11215499/b8eba865c931/d4ra00796d-f1.jpg

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