Computational Model-Based Analysis of Strategies to Enhance Scaffold Vascularization

*, Address correspondence to: Ali Cinar, PhD, Department of Chemical and Biological Engineering, Illinois Institute of Technology, , 10 West 33rd Street, Chicago, IL 60616, E-mail: [email protected]

Introduction

Cell-based approaches in tissue engineering require rapid and stable vascularization of biomaterials to regenerate tissues with high oxygen demand. However, clinical applications of cell-based approaches have been primarily limited to relatively avascular cartilage¹ or thin skin.² Well-developed vasculature is essential for almost all engineered tissues and is particularly challenging in thick tissues.³

Researchers have investigated a number of different strategies to establish vascular networks within biomaterials. These include: (i) optimizing design of physical and chemical scaffold architecture to enable or even enhance vessel growth, (ii) delivery of angiogenic factors to stimulate vessel growth from host tissue, and (iii) building vascular networks within the scaffold before implantation (in vitro prevascularization).^4,5 For the first strategy, a broad range of physical properties of the scaffold can result in biomaterials that are more permissive for directed and rapid vessel invasion.^6-10 Not only does pore size and porosity influence angiogenesis but also interconnectivity of the porous structure influences the rate of angiogenesis.¹¹

Delivery of angiogenic factors to target microenvironments in scaffolds to stimulate cell migration and proliferation can enhance vascularization.^12-15 A variety of angiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and/or platelet-derived growth factor (PDGF) have been delivered from scaffolds, aiming to enhance the vascularization process.^16-19

However, the typical approach to deliver growth factors (GFs) from scaffolds does not allow precise control over...