School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK.
Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK.
Mater Sci Eng C Mater Biol Appl. 2021 Oct;129:112375. doi: 10.1016/j.msec.2021.112375. Epub 2021 Aug 14.
Cardiovascular disease (CVD) is a general term for conditions which are the leading cause of death in the world. Quick restoration of tissue perfusion is a key factor to combat these diseases and improve the quality and duration of patients' life. Revascularization techniques include angioplasty, placement of a stent, or surgical bypass grafting. For the latter technique, autologous vessels remain the best clinical option; however, many patients lack suitable autogenous due to previous operations and they are often unsuitable. Therefore, synthetic vascular grafts providing antithrombosis, neointimal hyperplasia inhibition and fast endothelialization are still needed. To address these limitations, 3D printed dipyridamole (DIP) loaded biodegradable vascular grafts were developed. Polycaprolactone (PCL) and DIP were successfully mixed without solvents and then vascular grafts were 3D printed. A mixture of high and low molecular weight PCL was used to better ensure the integration of DIP, which would offer the biological functions required above. Moreover, 3D printing technology provides the ability to fabricate structures of precise geometries from a 3D model, enabling to customize the vascular grafts' shape or size. The produced vascular grafts were fully characterized through multiple techniques and the last step was to evaluate their drug release, antiplatelet effect and cytocompatibility. The results suggested that DIP was properly mixed and integrated within the PCL matrix. Moreover, these materials can provide a sustained and linear drug release without any obvious burst release, or any faster initial release rates for 30 days. Compared to PCL alone, a clear reduced platelet deposition in all the DIP-loaded vascular grafts was evidenced. The hemolysis percentage of both materials PCL alone and PCL containing 20% DIP were lower than 4%. Moreover, PCL and 20% DIP loaded grafts were able to provide a supportive environment for cellular attachment, viability, and growth.
心血管疾病（CVD）是世界上主要的死亡原因。快速恢复组织灌注是对抗这些疾病并提高患者生活质量和延长寿命的关键因素。再血管化技术包括血管成形术、支架置入或旁路移植术。对于后者技术，自体血管仍然是最佳的临床选择；然而，由于先前的手术，许多患者缺乏合适的自体血管，而且它们往往不合适。因此，仍然需要提供抗血栓、抑制新生内膜增生和快速内皮化的合成血管移植物。为了解决这些限制，开发了载双嘧达莫（DIP）的 3D 打印可生物降解血管移植物。聚己内酯（PCL）和 DIP 成功地在没有溶剂的情况下混合，然后 3D 打印血管移植物。使用高分子量和低分子量的 PCL 混合物，以更好地确保 DIP 的整合，这将提供上述所需的生物学功能。此外，3D 打印技术提供了从 3D 模型制造精确几何结构的能力，能够定制血管移植物的形状或尺寸。通过多种技术对所生产的血管移植物进行了全面表征，最后一步是评估其药物释放、抗血小板作用和细胞相容性。结果表明，DIP 被适当混合并整合到 PCL 基质中。此外，这些材料可以提供持续和线性的药物释放，而没有明显的突释或 30 天内任何更快的初始释放率。与单独的 PCL 相比，在所有载有 DIP 的血管移植物中都明显减少了血小板沉积。单独的 PCL 和含有 20% DIP 的 PCL 的溶血率均低于 4%。此外，PCL 和 20% DIP 负载的移植物能够为细胞附着、活力和生长提供支持环境。
