Monocyte chemoattractant protein-1 released from polycaprolactone/chitosan hybrid membrane to promote angiogenesis in vivo
Monocyte chemoattractant protein-1 released from polycaprolactone/chitosan hybrid membrane to promote angiogenesis in vivo
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DOI：
10.1177/0883911514554146
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发表时间：
2014-10
影响因子：
1.7
通讯作者：
Ju Zhang;Guoping Li;Shan Gao;Yao Yao-Yao;Li-yun Pang;Yuejie Li;Weiwei Wang;Qiang Zhao;D. Kong;Chen Li
中科院分区：
文献类型：
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作者：
Ju Zhang;Guoping Li;Shan Gao;Yao Yao-Yao;Li-yun Pang;Yuejie Li;Weiwei Wang;Qiang Zhao;D. Kong;Chen Li
我们制备了一种由聚己内酯和天然多糖壳聚糖组成的杂化膜。壳聚糖的掺入使材料能够通过肝素和壳聚糖之间的静电相互作用而肝素化。更重要的是，由于多种细胞因子已表现出对肝素的结合亲和力，聚己内酯/壳聚糖化合物的肝素化也促进了单核细胞趋化蛋白-1的固定，单核细胞趋化蛋白-1是一种已报道的促血管生成趋化因子。结果表明，肝素化的聚己内酯/壳聚糖膜与单核细胞趋化蛋白-1固定能够释放单核细胞趋化蛋白-1在一个控制和持续的方式。所释放的单核细胞趋化蛋白-1的生物活性未受到损害，如使用分离的大鼠外周血单核细胞的趋化室测定所示。增强局部血管生成，随后观察到在体内皮下植入肝素化的聚己内酯/壳聚糖膜与单核细胞趋化蛋白-1释放性能和单核细胞趋化蛋白-1的血管生成作用的机制进行了研究。我们提出，单核细胞趋化蛋白-1诱导的局部毛细血管形成是由于增加招聘的巨噬细胞，特别是交替激活的M2巨噬细胞，这已牵连在伤口愈合。此外，还观察到单核细胞趋化蛋白-1对血管生成的直接影响，主要是通过单核细胞趋化蛋白-1刺激血管内皮生长因子的表达和活性。总之，我们在这里报告了一种可行的方法来制造聚己内酯/壳聚糖杂交材料，可以与血管生成信号传导剂，如单核细胞趋化蛋白-1功能化。该材料植入体内可促进血管生成，有望成为治疗局部缺血损伤或皮肤创伤的支架材料或敷料材料。
We have fabricated a hybrid membrane composed of polycaprolactone and a natural polysaccharide, chitosan. The incorporation of chitosan enabled heparinization of the material via electrostatic interaction between heparin and chitosan. More importantly, since multiple cytokines have exhibited binding affinity towards heparin, heparinization of the polycaprolactone/chitosan compound also facilitated immobilization of monocyte chemoattractant protein-1, which is a well-reported pro-angiogenic chemokine. Results demonstrated that the heparinized polycaprolactone/chitosan membrane with monocyte chemoattractant protein-1 immobilization was able to release monocyte chemoattractant protein-1 in a controlled and sustained manner. Bioactivity of the released monocyte chemoattractant protein-1 was uncompromised as shown by a chemotaxis chamber assay using isolated rat peripheral blood mononuclear cells. Enhanced local angiogenesis was subsequently observed in vivo after subcutaneous implantation of the heparinized polycaprolactone/chitosan membrane with monocyte chemoattractant protein-1-releasing property and the mechanisms underlying the angiogenic role of monocyte chemoattractant protein-1 were also investigated. We propose that the monocyte chemoattractant protein-1-induced local capillary formation is attributable to increased recruitment of macrophages, particularly the alternatively activated M2 macrophages, which have been implicated in wound healing. Moreover, a direct effect of monocyte chemoattractant protein-1 on angiogenesis was also observed, mainly via monocyte chemoattractant protein-1-stimulated vascular endothelial growth factor expression and activity. In summary, we report here a feasible way to fabricate a polycaprolactone/chitosan hybrid material that could be functionalized with angiogenic signalling agents, such as monocyte chemoattractant protein-1. Implantation of this material promoted angiogenesis and may therefore be developed into scaffold or dressing materials in treating local ischemia injuries or cutaneous wound.