Engineered systems for therapeutic angiogenesis

•Delivery and retention of therapeutics near the ischemic site is crucial.•Biomaterials can induce angiogenesis, with or without additional factors.•Tailored release of angiogenic factors is crucial to therapeutic efficacy.•Paracrine secretion from implanted cells can perfuse ischemic tissue.

Ischemic disease caused by insufficient blood supply leads to a lack of oxygen and nutrients and a build-up of waste products in the affected tissue. Therapeutic angiogenesis, as a means to enhance perfusion of tissues with an inadequate blood supply, holds great promise for the treatment of ischemic disease. A wide range of factors that play a key role in physiological angiogenesis have been identified and trialed as pro-angiogenic agents. However, as yet pro-angiogenic treatments have failed to be translated clinically, owing to both lack of efficacy and safety concerns regarding the use of doses considerably larger than is typical present under physiological conditions. Thus, there is a clear need for the design and development of systems to overcome these hurdles and allow for the translation of safe and efficacious treatments to induce angiogenesis. In this regard, much progress has been made in the development of biomaterials as delivery systems for angiogenic factors to control the delivery and release of angiogenic therapies to induce vascularization. Thus, we review progress towards the development of translatable biomaterial-based systems to deliver angiogenic therapies, and point towards burgeoning advances in the field.