Hydrogel-based therapeutic angiogenesis: An alternative treatment strategy for critical limb ischemia

Critical limb ischemia (CLI) is the most severe clinical manifestation of peripheral arterial disease (PAD), resulting in the total or partial loss of limb function. Although the conventional treatment strategy of CLI (e.g., medical treatment and surgery) can improve blood perfusion and restore limb function, many patients are unsuitable for these strategies and they still face the threats of amputation or death. Therapeutic angiogenesis, as a potential solution for these problems, attempts to manipulate blood vessel growth in vivo for augment perfusion without the help of extra pharmaceutics and surgery. With the rise of interdisciplinary research, regenerative medicine strategies provide new possibilities for treating many clinical diseases. Hydrogel, as an excellent biocompatibility material, is an ideal candidate for delivering bioactive molecules and cells for therapeutic angiogenesis. Besides, hydrogel could precisely deliver, control release, and keep the bioactivity of cargos, making hydrogel-based therapeutic angiogenesis a new strategy for CLI therapy. In this review, we comprehensively discuss the approaches of hydrogel-based strategy for CLI treatment as well as their challenges, and future directions.