Liu Yang, Zhang Jiang, Wang Jian, Wang Yuan, Zeng Zheng, Liu Tao, Chen Junying, Huang Nan
Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, 610031, People's Republic of China.
J Biomed Mater Res A. 2015 Jun;103(6):2024-34. doi: 10.1002/jbm.a.35339. Epub 2014 Oct 14.
Coronary artery disease is a great threat to human health and is the leading killer worldwide. Percutaneous coronary intervention is the most effective therapy; however, thrombus, and restenosis caused by endothelium injury continue to be problematic after treatment. It is widely accepted that surface biofunctional modification to improve blood compatibility and accelerate endothelialization may be an effective approach to prevent the occurrence of adverse cardiac events. In this study, novel VEGF-loaded heparin/poly-L-lysine (Hep/PLL) particles were developed and immobilized on a dopamine coated titanium surface. The size, distribution, zeta potential, and morphology of the prepared particles were subsequently characterized. The influence of changes in the surface physicochemical properties after particle immobilization was assessed for blood compatibility and cytocompatibility. Surface-modified VEGF-loaded particles significantly inhibited platelet adhesion and activation and were effective in promoting the proliferation and survival of endothelial progenitor cells and endothelial cells. Moreover, Hep/PLL particles were also beneficial for controlling the long-term release of VEGF, which may facilitate endothelium regeneration. In conclusion, VEGF-loaded Hep/PLL particles were successfully immobilized on the Ti surface, and the biocompatibility was significantly improved. This study demonstrates a potential application for the multifunctional modification of stent surfaces for clinical use.
冠状动脉疾病对人类健康构成巨大威胁,是全球主要的杀手。经皮冠状动脉介入治疗是最有效的治疗方法;然而,血栓以及治疗后由内皮损伤引起的再狭窄仍然是问题。人们普遍认为,进行表面生物功能修饰以改善血液相容性并加速内皮化可能是预防不良心脏事件发生的有效方法。在本研究中,制备了负载血管内皮生长因子(VEGF)的新型肝素/聚-L-赖氨酸(Hep/PLL)颗粒,并将其固定在多巴胺涂层的钛表面。随后对制备的颗粒的大小、分布、zeta电位和形态进行了表征。评估了颗粒固定后表面物理化学性质变化对血液相容性和细胞相容性的影响。表面修饰的负载VEGF的颗粒显著抑制血小板粘附和活化,并有效促进内皮祖细胞和内皮细胞的增殖与存活。此外,Hep/PLL颗粒也有利于控制VEGF的长期释放,这可能有助于内皮再生。总之,负载VEGF的Hep/PLL颗粒成功固定在钛表面,生物相容性显著提高。本研究证明了支架表面多功能修饰在临床应用中的潜在应用价值。