Pacharra Sandra, McMahon Seán, Duffy Patrick, Basnett Pooja, Yu Wenfa, Seisel Sabine, Stervbo Ulrik, Babel Nina, Roy Ipsita, Viebahn Richard, Wang Wenxin, Salber Jochen
Salber Laboratory, Centre for Clinical Research, Department of Experimental Surgery, Ruhr-Universität Bochum, Bochum, Germany.
Laboratory A, Synergy Centre, Ashland Specialties Ireland Ltd., Dublin, Ireland.
Front Bioeng Biotechnol. 2020 Aug 13;8:991. doi: 10.3389/fbioe.2020.00991. eCollection 2020.
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 cyto- and hemocompatibility.
尽管与耐用材料相比，在支架生产中使用生物可吸收材料被认为能提高长期安全性，但美国食品药品监督管理局（FDA）最近一份关于首个获FDA批准的生物可吸收血管支架的2年随访报告显示，与金属对照相比，主要不良心脏事件和血栓形成的发生率有所增加。为了克服第一代生物可吸收聚合物的问题，采用一种新颖的一步聚乙二醇（PEG）功能化和共聚策略，开发了一系列具有不同丙交酯与己内酯含量的聚乙二醇功能化聚-L-丙交酯-共-ε-己内酯共聚物。这种方法代表了一种用于细胞相互作用表面增强的新的简便方式，通过就细胞毒性、溶血、血小板黏附、白细胞活化和内皮细胞黏附方面对这些材料的细胞和血液相容性进行筛选得以证明。通过改变丙交酯与己内酯聚合物组成，有可能逐渐影响内皮细胞和血小板黏附，这使得基于聚合物化学对生物学反应进行微调成为可能。除了PLCL-PEG 55:45的溶血率为2.5%±0.5外，所开发的所有聚合物均无细胞毒性，白细胞活化水平可接受，且呈现非溶血（溶血率<2%）行为。与未含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）的水接触角减小，而材料PCL-PEG550、PLCL-PEG550 90:10和PLCL-PEG550 70:30表现出最佳的内皮细胞黏附。从完成的一系列测试的细胞相容性角度来看，PLLA-PEG550和PLCL-PEG550 70:30是心血管植入应用的最佳候选材料。总体而言，由于这种一步合成策略易于转化为器件生产，且具有出色的细胞和血液相容性，这些聚合物是适用于支架制造的优秀创新材料。
