VEGF heparinized-decellularized adipose tissue scaffolds enhance tissue engineering vascularization in vitro

Abstract

Scaffolds based on decellularized adipose tissue (DAT) are gaining popularity in the adipose tissue engineering field due to their high biocompatibility and vascularizing properties. Previous studies involving decellularized adipose tissue (DAT) scaffolds have not fully demonstrated their ability to induce in vitro vascularization of engineered tissue. With the aim of developing a more effective adipose tissue engineering vascularization technique based on DAT, we investigated the vascularizing potential of a vascular endothelial growth factor (VEGF) delivery system utilizing a heparinized DAT (Hep-DAT) scaffold in vitro. To generate this system, heparins were cross-linked to DATs with 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide and N-hydroxysuccinimide. Encapsulated Hep-DATs were able to control the release of a significantly higher amount of VEGF in vitro than non-heparinized DATs. Human bone marrow stromal cells (hBMSCs), when seeded on these VEGF–Hep-DATs, differentiated into endothelial cells which expressed vascular endothelial markers CD34 and VWF, thus resulting in accelerated vascularization of transplanted tissue as compared to the control DAT-only scaffold. In conclusion, these studies demonstrate that VEGF–Hep-DATs promoted greater tissue vascularization as compared to the DAT control scaffold and that VEGF–Hep-DATs are an effective and biocompatible angiogenesis system.