ABSTRACT
Cardiovascular disease is the leading cause of death and disability in the United States and most Western countries. This mostly is due to the narrowing and eventual blockage of blood vessels to the normal Œow of blood, causing tissue ischemia and damage. As such, therapeutic interventions to treat cardiovascular disease include strategies to revascularize these ischemic tissues. Among the two most common surgical procedures for coronary or peripheral vascular disease are the placement of stents (to reopen narrowing vessels physically) or introduction of a bypass graft to circumvent diseased vessels. While such approaches have proven to be widely successful in cases where vascular disease is restricted to large vessels, in many settings, the limitation for blood Œow is in the microvasculature. In this setting, it is clear that the most promising approach is to promote the formation of additional microvessels in the ischemic tissue. In addition to what is now referred to as “therapeutic angiogenesis,” our ability to promote controlled neovascularization is also critical to the success of tissue engineering as a strategy for organ replacement. Currently, investigators have demonstrated a number of promising avenues to engineer cells and
6.1 Introduction .................................................................................................. 165 6.2 Regulation of Angiogenesis by the Microenvironment ................................ 166 6.3 Regulation of Angiogenesis by Cell Adhesion to Extracellular Matrix ....... 166 6.4 Mechanical Regulation of Angiogenesis ...................................................... 169 6.5 Engineered Materials to Promote Vascularization ....................................... 172 6.6 Multicellular Interactions in Angiogenesis ................................................... 176 6.7 Conclusion .................................................................................................... 179 Acknowledgments .................................................................................................. 180 References .............................................................................................................. 180
biomaterials to form tissue-like structures in culture. Our ability to translate these in vitro tissues into transplantable replacement tissues is now limited by our ability to promote the successful vascularization of the engineered constructs. As most cells must reside within 200 μm of the nearest capillary for proper gas exchange, nutrient delivery, and waste removal,1,2 a failure to vascularize an engineered implant would either result in massive failure of the implant or limit us to implant only tiny structures.
