A hydrophobic gelatin fiber sheet promotes secretion of endogenous vascular endothelial growth factor and stimulates angiogenesis

Abstract

In tissue engineering and regenerative medicine, the formation of vascular beds is an effective method to supply oxygen and nutrients to implanted cells or tissues to improve their survival and promote normal cellular functions. Various types of angiogenic materials have been developed by incorporating growth factors, such as vascular endothelial growth factor, in biocompatible materials. However, these exogenous growth factors suffer from instability and inactivation under physiological conditions. In this study, we designed a novel angiogenic electrospun fiber sheet (C16-FS) composed of Alaska pollock-derived gelatin (ApGltn) modified with hexadecyl (C16) groups to induce localized and sustained angiogenesis without growth factors. C16-FS was thermally crosslinked to enhance its stability. We demonstrated that C16-FS swells in phosphate-buffered saline for over 24 h and resists degradation. Laser doppler perfusion imaging showed that C16-FS induced increased blood perfusion when implanted subcutaneously in rats compared with unmodified ApGltn-fiber sheets (Org-FS) and the sham control. Furthermore, angiogenesis was sustained for up to 7 days following implantation. Immunohistochemical studies revealed elevated nuclear factor-κB and CD31 levels around the C16-FS implantation site compared with the Org-FS implantation site and the control incision site. These results demonstrate that C16-FS is a promising angiogenic material to promote the formation of vascular beds for cell and tissue transplantation without the need for growth factors.