Data_Sheet_1_Cytocompatibility Evaluation of a Novel Series of PEG-Functionalized Lactide-Caprolactone Copolymer Biomaterials for Cardiovascular Applications.pdf

Although the use of bioresorbable materials in stent production is thought to improve long-term safety compared to their durable counterparts, a recent FDA report on the 2-year follow-up of the first FDA-approved bioresorbable vascular stent showed an increased occurrence of major adverse cardiac events and thrombosis in comparison to the metallic control. In order to overcome the issues of first generation bioresorbable polymers, a series of polyethylene glycol-functionalized poly-L-lactide-co-ε-caprolactone copolymers with varying lactide-to-caprolactone content is developed using a novel one-step PEG-functionalization and copolymerization strategy. This approach represents a new facile way toward surface enhancement for cellular interaction, which is shown by screening these materials regarding their cyto- and hemocompatibility in terms of cytotoxicity, hemolysis, platelet adhesion, leucocyte activation and endothelial cell adhesion. By varying the lactide-to-caprolactone polymer composition, it is possible to gradually affect endothelial and platelet adhesion which allows fine-tuning of the biological response based on polymer chemistry. All polymers developed were non-cytotoxic, had acceptable leucocyte activation levels and presented non-hemolytic (<2% hemolysis rate) behavior except for PLCL-PEG 55:45 which presented hemolysis rate of 2.5% ± 0.5. Water contact angles were reduced in the polymers containing PEG functionalization (PLLA-PEG: 69.8° ± 2.3, PCL-PEG: 61.2° ± 7.5) versus those without (PLLA: 79.5° ± 3.2, PCL: 76.4° ± 10.2) while the materials PCL-PEG550, PLCL-PEG550 90:10 and PLCL-PEG550 70:30 demonstrated best endothelial cell adhesion. PLLA-PEG550 and PLCL-PEG550 70:30 presented as best candidates for cardiovascular implant use from a cytocompatibility perspective across the spectrum of testing completed. Altogether, these polymers are excellent innovative materials suited for an application in stent manufacture due to the ease in translation of this one-step synthesis strategy to device production and their excellent in vitro cyto- and hemocompatibility.

尽管相较于永久性支架材料，在支架制备中使用生物可吸收材料（bioresorbable materials）被认为可提升长期安全性，但美国食品药品监督管理局（FDA）近期发布的首项获批生物可吸收血管支架的2年随访报告显示，与金属对照组相比，该支架的主要不良心脏事件与血栓形成发生率有所升高。为克服第一代生物可吸收聚合物存在的问题，本研究采用新型一步法聚乙二醇（polyethylene glycol, PEG）功能化与共聚策略，制备了一系列丙交酯与己内酯比例可变的聚乙二醇功能化聚L-丙交酯-ε-己内酯共聚物（polyethylene glycol-functionalized poly-L-lactide-co-ε-caprolactone）。该方法为实现细胞相互作用的表面改性提供了一种简便的新途径，研究通过检测这些材料的细胞相容性与血液相容性，评估了其细胞毒性、溶血性能、血小板黏附、白细胞活化以及内皮细胞黏附情况。通过调整丙交酯与己内酯的聚合物组成比例，可逐步调控内皮细胞与血小板的黏附行为，从而能够基于聚合物化学组成精准调节生物响应。所有合成的聚合物均无细胞毒性，白细胞活化水平处于可接受范围，且表现出非溶血（溶血率<2%）特性，仅PLCL-PEG 55:45的溶血率为2.5%±0.5。与未进行PEG功能化的聚合物（聚L-丙交酯PLLA：79.5°±3.2；聚己内酯PCL：76.4°±10.2）相比，含PEG功能化的聚合物（PLLA-PEG：69.8°±2.3；PCL-PEG：61.2°±7.5）的水接触角有所降低；其中PCL-PEG550、PLCL-PEG550 90:10与PLCL-PEG550 70:30表现出最优的内皮细胞黏附性能。从完成的全部细胞相容性测试来看，PLLA-PEG550与PLCL-PEG550 70:30是心血管植入器械应用的最佳候选材料。综上，由于该一步合成策略可便捷地转化为器械量产工艺，且这些聚合物具备优异的体外细胞与血液相容性，因此它们是适用于支架制备的优质创新材料。