School of Mechanical Engineering, YONSEI University, Seoul 03722, South Korea.
Division of Cardiovascular Surgery, Severance Cardiovascular Hospital, YONSEI University College of Medicine, Seoul 03722, South Korea.
J Control Release. 2021 Dec 10;340:125-135. doi: 10.1016/j.jconrel.2021.10.024. Epub 2021 Oct 22.
Various perivascular drug delivery techniques have been demonstrated for localized post-treatment of intimal hyperplasia: a vascular inflammatory response caused by endothelial damages. Although most perivascular devices have focused on controlling the delivery duration of anti-proliferation drug, the confined and unidirectional delivery of the drug to the target tissue has become increasingly important. In addition, careful attention should also be paid to the luminal stability and the adequate exchange of vascular protein or cell between the blood vessel and extravascular tissue to avoid any side effect from the long-term application of any perivascular device. Here, a highly flexible and porous silk fibroin microneedle wrap (Silk MN wrap) is proposed to directly inject antiproliferative drug to the anastomosis sites while ensuring sufficient vascular exchanges. Drug-embedded silk MNs were transfer-molded on a highly flexible and porous silk wrap. The enhanced cell compatibility, molecular permeability, and flexibility of silk MN wrap guaranteed the structural integrity of blood vessels. Silk wrap successfully supported the silk MNs and induced multiple MN penetration to the target tissue. Over 28 days, silk MN wrap significantly inhibited intimal hyperplasia with a 62.1% reduction in neointimal formation.
这是一种由内皮损伤引起的血管炎症反应。虽然大多数血管周围装置都集中在控制抗增殖药物的输送持续时间上,但药物向靶组织的受限和单向输送变得越来越重要。此外,还应仔细注意管腔的稳定性以及血管蛋白或细胞在血管和血管外组织之间的充分交换,以避免任何血管周围装置的长期应用带来的任何副作用。在这里,提出了一种高度灵活和多孔的丝素蛋白微针包裹物(Silk MN wrap),以在确保充分血管交换的同时,将抗增殖药物直接注射到吻合部位。药物嵌入的丝素微针通过转移模塑在高度灵活和多孔的丝素包裹物上。丝素 MN 包裹物的增强细胞相容性、分子通透性和柔韧性保证了血管的结构完整性。丝素包裹物成功地支撑了丝素微针,并诱导多个微针穿透到靶组织。在 28 天的时间里,丝素 MN 包裹物显著抑制了内膜增生,新生内膜形成减少了 62.1%。