School of Materials Science & Engineering, Beijing Institution of Technology, Beijing 100081, China.
Beijing Key Laboratory of Construction Tailorable Advanced Functional Materials and Green Applications, Beijing 100081, China.
ACS Appl Bio Mater. 2021 Mar 15;4(3):2373-2384. doi: 10.1021/acsabm.0c01225. Epub 2021 Feb 9.
Hydrogel complex scaffolds (hydrogel scaffolds) are prepared by coating precursor solutions onto heparin-modified poly(ε-caprolactone) (PCLH) scaffolds followed by subsequent in situ gelation. Here, we show that hydrogel complexation can significantly strengthen the scaffold and slow its degradation. The hydrogel scaffold was implanted into the abdominal aorta of a rat model, and the aneurysm incidence rate of the hydrogel scaffolds sharply decreased compared with that of the hydrogel-free scaffolds. Histological and immunohistological analyses showed that the implanted grafts had good vascular regeneration. The absence of calcification and occurrence of contractile smooth muscle cells (SMCs) at the first month was found in the hydrogel-free PCLH scaffold due to the presence of surface-modified heparin, whereas the hydrogel scaffold exhibited mild calcification and later occurrence of contractile SMCs as the complexed hydrogel covered the fibers and blocked the interaction between heparin and cells. Heparin was further physically encapsulated into the hydrogel before gelation, and its sustainable release was demonstrated by an in vitro release test. A pilot implantation in a rabbit carotid model showed that the encapsulated heparin modulated the scaffold characteristics including anticoagulation, anticalcification, and the early occurrence of contractile SMCs in vivo. Consequently, hydrogel complexation can significantly improve the in vivo regeneration property of the scaffold due to its multiple beneficial characteristics.
水凝胶复合支架(水凝胶支架)是通过将前体溶液涂覆到肝素修饰的聚(ε-己内酯)(PCLH)支架上,然后进行原位凝胶化来制备的。在这里,我们表明水凝胶的复合可以显著增强支架并减缓其降解。将水凝胶支架植入大鼠腹主动脉模型中,与无凝胶支架相比,水凝胶支架的动脉瘤发生率明显降低。组织学和免疫组织化学分析表明,植入的移植物具有良好的血管再生。由于存在表面修饰的肝素,无凝胶的 PCLH 支架在第一个月就出现了无钙化和收缩性平滑肌细胞(SMC)的发生,而水凝胶支架则表现出轻度的钙化和随后的收缩性 SMC 的发生,因为复合水凝胶覆盖了纤维并阻止了肝素与细胞之间的相互作用。肝素在凝胶化之前进一步物理包封到水凝胶中,并通过体外释放试验证明了其可持续释放。在兔颈动脉模型中的初步植入表明,包封的肝素调节了支架的特性,包括抗凝、抗钙化和体内收缩性 SMC 的早期发生。因此,由于其多种有益特性,水凝胶的复合可以显著改善支架的体内再生性能。