Extracellular matrix sheet modified with VEGF-loaded nanoparticles for bladder regeneration

Abstract

Extracellular matrix (ECM) bioscaffolds have been widely studied to repair bladder tissue defects; however, insufficient angiogenesis and weak mechanical strength limit their applicability for tissue regeneration. In this work, ECM bioscaffolds were derived from decellularized sheets and then modified with vascular endothelial growth factor (VEGF)-conjugated superparamagnetic iron oxide nanoparticles (Fe3O4 NP–VEGF) to promote angiogenesis. Electrospun silk fibroin (SF) is a natural biocompatible protein with excellent mechanical properties. To further improve the mechanical properties of ECM bioscaffolds, SF was added to the Fe3O4 NP–VEGF-modified ECM bioscaffolds to develop a biomimetic ECM-like proangiogenic scaffold. In vitro characterization with endothelial cells revealed that the proangiogenic scaffold supports cell adhesion and proliferation. Furthermore, the biomimetic proangiogenic scaffold significantly accelerated vascularization in vivo in a rat bladder augmentation model. Importantly, these improvements in vascularization promoted urothelium and smooth muscle regeneration. These findings demonstrate that the developed biomimetic proangiogenic scaffold possesses great potential for bladder regeneration applications.