CeramStent2: novel ceramic-metal coatings for coronary implants to reduce local thrombotic events and to improve the hemocompatible behavior, mechanical stability and chemical long-time resistance

在该项目的第一阶段，成功地开发了涂层工艺和材料成分。在材料方面，主要创造了改善血液相容性的基本先决条件。结果表明，可以获得高含量的陶瓷纳米颗粒梯度复合涂层。在细胞生物学方面，建立和优化了血管内皮细胞培养和血小板培养，并对L929小鼠成纤维细胞和内皮细胞进行了符合ISO10993-5标准的细胞毒性研究。该项目第一年的联合开发工作已经为涂层工艺的专利申请做出了贡献。目前正在进行血液相容性测试，以验证涂层支架材料的血液相容性。上一次申请的相应里程碑预计将按计划在21个月后达到，或由于CORONA稍有延迟而达到。根据当前项目的结果，首先需要进一步研究采用电镀方法的新型梯度复合涂层，以及血细胞的激活和它们在陶瓷涂层支架上的相互作用，以及它们对活体相邻平滑肌细胞表型的影响。具体项目目标是：1.现代金属-陶瓷涂层的开发和表征2。陶瓷纳米颗粒的分级，支架扩张时涂层与亚表面的适配。分析复合涂层对相关细胞类型的毒性、黏附和活化的影响。绵羊细胞培养方法的建立为体内大动物模型的建立做准备优化复合涂层，以期成功内化6。优化复合涂层，以支持平滑肌细胞的收缩表型(而不是合成表型)7。体内实验：评估载脂蛋白E基因敲除大鼠模型中支架原型的可植入性8。体内试验：评价支架的有效性和安全性

In the first phase of the project, the coating process and the material composition were successfully developed. On the material side, the basic prerequisites for improving hemocompatibility were primarily created. It was shown that a graded composite coating with a high content of ceramic nanoparticles can be carried out. In terms of cell biology, endothelial cell cultures and platelet cultures were established and optimized, and cytotoxicity studies in accordance with ISO10993-5 were carried out with L929 mouse fibroblasts and endothelial cells. The joint development work in the first year of the project has already contributed to the patenting of the coating process. Hemocompatibility tests are currently running to validate the blood compatibility of the coated stent materials. The corresponding milestone from the previous application is expected to be reached after 21 months as planned or due to Corona with a slight delay. Based on the results of the current project, there is above all a need for further research with regard to research into new types of graded composite coatings by means of galvanic deposition and with regard to the activation of blood cells and their interaction on the ceramic-coated stents, as well as their influence on the phenotype of adjacent smooth muscle cells in vivo.Specific project goals are:1. Development and characterization of modern metal-ceramic coatings2. Grading of the ceramic nanoparticles, adaptation of the coating to the subsurface when the stent expands3. Analyzes of the influence of composite coatings on toxicity, adhesion andactivation of relevant cell types4. Establishment of ovine cell cultures in preparation for the in vivo large animal model5. Optimization of the composite coatings with a view to successfulEndothelialization6. Optimization of the composite coatings with a view to supporting thecontractile phenotype (rather than the synthetic phenotype) of smooth muscle cells7. In vivo experiments: Evaluation of the implantability of stent prototypes in the ApoE knockoutRat model8. In vivo tests: evaluation of stent effectiveness and safety