Therapeutic angiogenesis based on injectable hydrogel for protein delivery in ischemic heart disease

Ischemic heart disease (IHD) remains the leading cause of death and disability worldwide and leads to myocardial necrosis and negative myocardial remodeling, ultimately leading to heart failure. Current treatments include drug therapy, interventional therapy, and surgery. However, some patients with severe diffuse coronary artery disease, complex coronary artery anatomy, and other reasons are unsuitable for these treatments. Therapeutic angiogenesis stimulates the growth of the original blood vessels by using exogenous growth factors to generate more new blood vessels, which provides a new treatment for IHD. However, direct injection of these growth factors can cause a short half-life and serious side effects owing to systemic spread. Therefore, to overcome this problem, hydrogels have been developed for temporally and spatially controlled delivery of single or multiple growth factors to mimic the process of angiogenesis in vivo. This paper reviews the mechanism of angiogenesis, some important bioactive molecules, and natural and synthetic hydrogels currently being applied for bioactive molecule delivery to treat IHD. Furthermore, the current challenges of therapeutic angiogenesis in IHD and its potential solutions are discussed to facilitate real translation into clinical applications in the future.