Biopolymeric delivery matrices for angiogenic growth factors
The development of new therapeutic approaches that aim to help the body exert its natural mechanisms for vascularized tissue growth (therapeutic angiogenesis) has become one of the most active areas of tissue engineering. Through basic research, several growth factor families and cytokines that are capable to induce physiological blood vessel formation have been identified. Indeed, preclinical and clinical investigations have indicated that therapeutic administration of angiogenic factors, such as the prototypic vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF), to sites of ischemia in the heart or the limb can improve regional blood flow. For new and lasting tissue vascularization, prolonged tissue exposure to these factors could be critical. Furthermore, as shown for VEGF, dosage must be tightly controlled, as excess amounts of VEGF can cause severe vascular leakage and hypotension. This review emphasizes natural and synthetic polymer matrices with respect to their development as vehicles for local and controlled delivery of angiogenic proteins, such as VEGF and bFGF, and their clinical applicability. In the dawn of experimental vascular engineering, new biomaterial schemes for clinical growth factor administration that take better account of biological principles of angiogenic growth factor function and the cell biological basis necessary to produce functional vasculature are evolving. Alongside their base function as protective embedment for angiogenic growth factors, these new classes of bioactive polymers are engineered with additional functionalities that better preserve growth factor activity and more closely mimic the in vivo release mechanisms and profiles of angiogenic growth factors from the extracellular matrix (ECM). Consequently, the preparation of both natural or completely synthetic materials with biological characteristics of the ECM has become central to many tissue engineering approaches that aim to deliver growth factors in a therapeutically efficient mode. Another promising venue to improve angiogenic performance is presented by biomaterials that allow sequential delivery of growth factors with complementary roles in blood vessel initiation and stabilization.