Vascularization strategies in tissue engineering approaches for soft tissue repair

Insufficient vascularization during tissue repair is often associated with poor clinical outcomes. This is a concern especially when patients have critical-sized injuries, where the size of the defect restricts vascularity, or even in small defects that have to be treated under special conditions, such as after radiation therapy (relevant to tumor resection) that hinders vascularity. In fact, poor vascularization is one of the major obstacles for clinical application of tissue engineering methods in soft tissue repair. As a key issue, lack of graft integration, caused by inadequate vascularization after implantation, can lead to graft failure. Moreover, poor vascularization compromises the viability of cells seeded in deep portions of scaffolds/graft materials, due to hypoxia and insufficient nutrient supply. In this article we aim to review vascularization strategies employed in tissue engineering techniques to repair soft tissues. For this purpose, we start by providing a brief overview of the main events during the physiological wound healing process in soft tissues. Then, we discuss how tissue repair can be achieved through tissue engineering, and considerations with regards to the choice of scaffold materials, culture conditions, and vascularization techniques. Next, we highlight the importance of vascularization, along with strategies and methods of prevascularization of soft tissue equivalents, particularly cell-based prevascularization. Lastly, we present a summary of commonly used in vitro methods during the vascularization of tissue-engineered soft tissue constructs.