Angiogenesis is important for supplying oxygen and nutrients to implanted cells and organs and thereby promoting their survival. However, exogenously administered growth factors such as vascular endothelial growth factor (VEGF) have a short half-life and are unstable under physiological conditions. In the present study, we developed an angiogenesis-inducing hydrogel by modifying Alaska pollock-derived gelatin with a dodecyl group (C12-ApGltn), and demonstrated that it is biodegradable and highly fluid at room temperature (25°C). C12-ApGltn dissolved in phosphate-buffered saline at 20 w/v% formed a self-assembling hydrogel with thixotropic properties that stimulated VEGF secretion by macrophage-like RAW264 cells. Moreover, C12-ApGltn stimulated nuclear factor-κB and VEGF expression when subcutaneously injected into mice and increased the cluster of differentiation 31-positive area compared with injection of unmodified ApGltn and phosphate-buffered saline control in the absence of any growth factors. Hematoxylin and eosin staining confirmed vascular capillaries around the C12-ApGltn injection site. These results demonstrate that C12-ApGltn hydrogel is a promising angiogenic material for clinical applications that can stimulate endogenous VEGF expression without requiring additional growth factors.

中文翻译：

---

基于疏水改性的阿拉斯加鳕鱼明胶的无生长因子，血管生成水凝胶。

血管生成对于向植入的细胞和器官供应氧气和营养，从而促进其存活至关重要。但是，外源性生长因子，例如血管内皮生长因子（VEGF），半衰期短，并且在生理条件下不稳定。在本研究中，我们通过用十二烷基（C12-ApGltn）修饰阿拉斯加波洛克派生的明胶来开发诱导血管生成的水凝胶，并证明它在室温（25°C）下可生物降解且流动性高。C20-ApGltn以20 w / v％的浓度溶于磷酸盐缓冲液中，形成具有触变性的自组装水凝胶，可刺激巨噬细胞样RAW264细胞分泌VEGF。而且，与没有任何生长因子的情况下未经修饰的ApGltn和磷酸盐缓冲液对照的注射相比，皮下注射到小鼠中时，C12-ApGltn刺激了核因子-κB和VEGF的表达，并增加了31阳性分化区域的簇。苏木精和曙红染色证实了C12-ApGltn注射部位周围的血管毛细血管。这些结果表明，C12-ApGltn水凝胶是一种有前途的血管生成材料，可用于临床应用，可刺激内源性VEGF表达，而无需其他生长因子。