Engineering Biomaterials-based Approaches for Better Angiogenesis

Abstract

Tissue engineering promises to solve the ever-increasing organ donor shortage, as well as to provide personalized and customized cures for numerous life-threatening diseases and organ/tissue failures. While significant advances have been made in recent years, most tissue engineering applications face a common roadblock that holds them back from being translated in the clinic: the inability to engineer constructs that would support sufficient and rapid blood vessel formation (angiogenesis) upon implantation. Most tissues cannot survive nor function properly without elaborate blood vessel networks in place. Thus, the goal of this work is to modify and examine two commonly used biomaterials, polycaprolactone (PCL) and gelatin, that would enhance blood vessel formation in vitro and in vivo through different mechanisms. The first approach was to incorporate reactive oxygen species (ROS)-degradable peptide into PCL scaffolds that would allow better cell infiltration, which led to improved angiogenesis. In the second approach, by modifying gelatin to form a thermostable hydrogel, a novel interaction between gelatin hydrogel and mesenchymal stem cells (MSC) that drove MSC differentiation into blood vessel-forming endothelial cells was discovered and examined. This dissertation work is aimed at overcoming the common barrier for clinical translation of tissue engineering, and the findings and the resulting design principles can be applied in various tissue engineering applications to accelerate clinical translation.