料植入体内后会引起炎性反应，其分泌的内源性生长因子对募集内皮细胞并诱导血管新生至关重要。然而，不可控的炎性反应同样会引起瘢痕组织的形成并阻碍新生血管的长入和损伤修复。而通过材料本身的生物学效应可控调节体内微环境，有效诱导原位血管化的形成及其作用机制尚无报道。

作者发现SCS调控血管新生主要与巨噬细胞有关，其可有效募集M2型巨噬细胞并诱导其分泌血管内皮生长因子（VEGF）。而SCS促进血管化相关行为的发生主要通过调控巨噬细胞中VEGF的分泌上调内皮细胞表面VEGFR2磷酸化的表达。而在条件培养基中分别加入VEGF抗体和VEGFR2抑制剂会明显削弱这种促进作用。

基于此，华东理工大学刘昌胜院士和王靖教授课题组发现了类肝素多糖磺化壳聚糖（SCS）在无外源性生长因子的参与下，通过调控巨噬细胞内源性生长因子的分泌可有效诱导缺血下肢中功能性血管的重建及贯通血流的恢复，并详细解析了其作用机制。

The endogenous growth factors secreted by the materials are very important for the recruitment of endothelial cells and the induction of angiogenesis. However, uncontrollable inflammatory reaction can also lead to the formation of scar tissue and hinder the growth and repair of neovascularization. However, there is no report on the formation and mechanism of in situ vascularization through the biological effect of materials.

We found that the regulation of angiogenesis by SCS is mainly related to macrophages, which can effectively recruit M2 macrophages and induce them to secrete vascular endothelial growth factor (VEGF). SCS promotes vascularization related behaviors mainly by regulating the secretion of VEGF in macrophages and up regulating the expression of VEGFR2 phosphorylation on endothelial cells. However, adding VEGF antibody and VEGFR2 inhibitor to the conditioned medium could significantly weaken the promoting effect.

 

Based on this, academician Liu Changsheng and Professor Wang Jing of East China University of science and technology found that heparin like polysaccharide sulfonated chitosan (SCS) can effectively induce the reconstruction of functional blood vessels and the recovery of perforating blood flow in ischemic lower limbs by regulating the secretion of macrophage endogenous growth factor without the participation of exogenous growth factor, The mechanism of action was analyzed in detail.

DOI: 10.1126/sciadv.abd8217

韩春雨