血管生长素
壳聚糖
血管生成
新生血管
细胞生物学
细胞因子
生物材料
体内
免疫系统
化学
组织工程
材料科学
免疫学
生物医学工程
癌症研究
纳米技术
生物
医学
生物化学
生物技术
作者
Xianzhen Yin,Yiting Li,Yingqi Chen,Peng Liu,Bo Feng,Peng Zhang,Hui Zeng
标识
DOI:10.1016/j.ijbiomac.2023.123486
摘要
Vascularization remains a major challenge in tissue engineering. In tissue repair with the involvement of biomaterials, both the material properties and material-induced immune response can affect angiogenesis. However, there is a scarcity of research on biomaterials that modulate angiogenesis simultaneously from both perspectives. Meanwhile, the effects and mechanisms of biomaterial-induced macrophages on angiogenesis remain controversial. In this study, a cytokine-controlled release system from our previous work was employed, and the effects thereof on angiogenesis through both direct and indirect means were investigated. Alginate/chitosan multilayer films were fabricated on interleukin (IL)-4-loaded titania nanotubes to achieve a sustained release of IL-4. The released IL-4 and the multilayers synergistically promoted angiogenic behaviors of endothelial cells (ECs), while up-regulating the expression of early vascular markers. Furthermore, polarized macrophages (both M1 and M2) notably elevated the expression of late vascular markers in ECs via the high expression of pro-maturation factor angiogenin-1. After subcutaneous implantation, the IL-4-loaded implants induced increased neovascularization in a short period, with the surrounding tissue returning to normal at the later stage. Therefore, the proposed IL-4-loaded implants exhibited superior pro-angiogenic capability in vitro and in vivo through both direct stimulation of ECs and the indirect induction of a suitable immune microenvironment.
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