Growth factor-free, angiogenic hydrogel based on hydrophobically modified Alaska pollock gelatin

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.