Wei Zhongling, Tian Peng, Liu Xuanyong, Zhou Bangxin
Institute of Materials, Shanghai University, Shanghai 200072, P.R. China.
State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, P.R. China.
Colloids Surf B Biointerfaces. 2014 Sep 1;121:451-60. doi: 10.1016/j.colsurfb.2014.06.036. Epub 2014 Jun 21.
Biodegradable magnesium and its alloys have attracted much attention, as they have been used as cardiovascular stents recently because of their biodegradation after implantation. However, their corrosion resistance, hemocompatibility and surface biocompatibility are needed for practical applications. In this work, heparinization of the plasma electrolytic oxidation/poly(l-lactic acid) (PEO/PLLA) composite coating on biodegradable AZ31 alloy was achieved by the strong adhesion of mussel-inspired polydopamine (PDAM). The corrosion resistance of the coated substrates was evaluated in simulated body fluid. In particular, the hemolysis ratio and platelet adhesion tests were conducted to evaluate the hemocompatibility of the composite coatings. The in vitro cytotoxicity of the composite coatings was evaluated with human umbilical vein endothelial cells (HUVECs). The adhesion and proliferation of HUVECs and human umbilical artery smooth muscle cells (HUASMCs) directly incubated on the composite coatings were also investigated. The results showed that although PDAM modification and further heparinization reduced the corrosion resistance of the PEO/PLLA composite coating, the protection of the coating for the substrate was mainly maintained. Moreover, PDAM modification and further heparinization significantly suppressed the adhesion of platelets and had little influence on sustaining a low hemolysis ratio thus resulting in good surface hemocompatibility of the composite coating. The in vitro cell test demonstrated that none of the composite coatings presented obvious cytotoxicity. Significantly, after surface heparinization, the composite coating became more suitable for HUVEC growth and simultaneously inhibited HUASMC growth. The results show that further modification of the PEO/PLLA composite coating on biodegradable magnesium alloy is a promising method to obtain good surface hemocompatibility for anticoagulation and to regulate the cell fate for fast re-endothelialization while sustaining the corrosion resistance of biodegradable magnesium-based cardiovascular stents.
可生物降解镁及其合金因其植入后可生物降解，最近被用作心血管支架，从而备受关注。然而，其实际应用需要具备耐腐蚀性、血液相容性和表面生物相容性。在本研究中，通过具有贻贝启发作用的聚多巴胺（PDAM）的强附着力，实现了可生物降解AZ31合金上的等离子体电解氧化/聚（L-乳酸）（PEO/PLLA）复合涂层的肝素化。在模拟体液中评估了涂层基体的耐腐蚀性。特别地，进行了溶血率和血小板黏附试验以评估复合涂层的血液相容性。用人脐静脉内皮细胞（HUVECs）评估了复合涂层的体外细胞毒性。还研究了直接接种在复合涂层上的HUVECs和人脐动脉平滑肌细胞（HUASMCs）的黏附和增殖情况。结果表明，尽管PDAM改性和进一步肝素化降低了PEO/PLLA复合涂层的耐腐蚀性，但涂层对基体的保护作用仍基本得以保持。此外，PDAM改性和进一步肝素化显著抑制了血小板的黏附，并且对维持低溶血率影响不大，从而使复合涂层具有良好的表面血液相容性。体外细胞试验表明，所有复合涂层均未表现出明显的细胞毒性。值得注意的是，表面肝素化后，复合涂层更适合HUVEC生长，同时抑制HUASMC生长。结果表明，对可生物降解镁合金上的PEO/PLLA复合涂层进行进一步改性，是一种有前景的方法，可在维持可生物降解镁基金属心血管支架耐腐蚀性的同时，获得良好的表面血液相容性以实现抗凝，并调节细胞命运以实现快速再内皮化。
