Regeneration of coronary arterial system using biodegradable hydrogel combined with angiogenic growth factor

本研究试图利用可生物降解的水凝胶纤维和血管生成生长因子，建立与天然冠状动脉连接的新型动脉网络。本实验先用血管生成生长因子处理水凝胶纤维，然后用静脉导管插入心肌瘘。在纤维的吸收过程中，瘘管的管腔表面内衬内皮细胞。同时，释放的血管生成生长因子有望促进血管生成和动脉生成，这些血管生成和动脉生成与新形成的心肌瘘相通。为此，使用杂种狗对几种水凝胶和血管生成因子进行了评估。带负电荷的透明质酸容易与带正电荷的碱性成纤维细胞生长因子（b-FGF）形成离子键。在体内，透明质酸凝胶在2周后逐渐释放b-FGF并增强血管生成，而不会引起炎症反应。带正电荷的壳聚糖与血小板源性内皮细胞生长因子（PD-ECGF）基因稳定结合。壳聚糖凝胶虽逐渐释放PD-ECGF基因，促进血管生成，但不被吸收，在周围组织中引起强烈的炎症反应。壳聚糖/聚乙烯醇凝胶提供了最有希望的结果，因为它在2周时导致瘘管形成和血管生成增强，炎症反应最小。

This study was performed in an attempt to create a new arterial network which has connection with native coronary arteries by using biodegradable hydrogel fiber and angiogenic growth factor. In this experiment, hydrogel fiber was first treated with angiogenic growth factor and then was inserted into the myocardial fistula with a venous catheter. During absorption of the fiber, the luminal surface of the fistula became lined with endothelial cells. At the same time, released angiogenic growth factor was expected to enhance angiogenesis and arteriogenesis which are in communication with the newly developed myocardial fistula. For this purpose, several hydrogels and angiogenic factors were evaluated using mongrel dogs. Hyaluronic acid, which charged negatively, made ionic bond easily with positively charged basic fibroblast growth factor (b-FGF). In vivo, hyaluronic acid gel gradually released b-FGF and enhanced angiogenesis at 2 weeks without eliciting inflammatory responses. Chitosan, which charged positively, made stable bonding with platelet derived endothelial cell growth factor (PD-ECGF) gene. Although chitosan gel gradually released PD-ECGF gene which enhanced angiogenesis, it was not absorbed and caused potent inflammatory reaction in the surrounding tissue. Chitosan/polyvinyl alcohol gel provided the most promising results because it leads to the fistula formation as well as the enhanced angiogenesis with minimum inflammatory reaction at 2 weeks.