Promoting early neovascularization of SIS-repaired abdominal wall by controlled release of bioactive VEGF

Abstract

Insufficient early neovascularization post-operation is thought to be the main reason of surgical recurrence of porcine small intestinal submucosa (SIS)-repaired abdominal wall defects. The controlled release of exogenous angiogenic growth factors (GFs) from biocompatible carriers is a possible way to solve this problem. In the present study, dextran nanoparticles (DNPs) loaded with vascular endothelial growth factor 165 (VEGF165) were pre-formulated by dual-aqueous phase separation method and then electrospun into the poly(lactic-co-glycolic acid) (PLGA) polymer fibers. The aim of this material is to release VEGF in a sustained manner with the degradation of PLGA and maintain its bioactivity concurrently. The prepared VEGF/DNPs-PLGA membrane was sandwiched by dual-layer SIS to construct a SIS-DNPs/VEGF-PLGA-SIS (SVDPS) composite scaffold. The in vitro study showed that the VEGF/DNPs-PLGA obtained higher VEGF encapsulation efficiency as well as better release property and bioactivity than the emulsion electrospun VEGF-PLGA and PLGA fibrous membranes by ELISA and HUVEC proliferation. The in vivo study showed that the SVDPS composite scaffold promoted significantly higher early therapeutic neovascularization within 2 weeks post-surgery than SIS-VEGF-PLGA-SIS (SVPS) and SIS-PLGA-SIS (SPS) by immunohistochemical and immunoblotting examination.