Self-assembled dodecyl group-modified gelatin microparticle-based hydrogels with angiogenic properties

Abstract

AbstractSupplying oxygen and nutrients to implanted cells or tissues is an important factor that improves their survivability and function in regenerative medicine. Various efforts have been made to develop angiogenic materials by incorporating and releasing growth factors such as vascular endothelial growth factor (VEGF). However, these exogenous growth factors have a short half-life under physiological conditions. We therefore designed a novel angiogenic microparticle (C12-MP) comprising Alaska pollock-derived gelatin (ApGltn) modified with a dodecyl group (C12-ApGltn) to stimulate endogenous VEGF secretion. The C12-MP suspension formed an injectable hydrogel, the rheological properties and enzymatic degradation of which were evaluated. RAW264 cells, mouse macrophage-like cells, cultured with C12-MPs, secreted significantly more VEGF than the original ApGltn MPs. Based on laser Doppler perfusion imaging, the C12-MP hydrogel clearly induced increased blood perfusion in a subcutaneous mouse model compared with the original ApGltn microparticle (Org-MP) or phosphate-buffered saline controls. Histological studies revealed that the areas of nuclear factor (NF)-κB, CD31, and myeloperoxidase staining showed a greater increase at the site injected with C12-MPs than at the site injected with the original ApGltn microparticles or phosphate-buffered saline. The C12-MP hydrogel is a promising angiogenic material for constructing vascular beds for cell transplantation by promoting endogenous VEGF secretion without additional growth factors.