A schematic of cell release mechanism out of the hydrogelIschemic vascular disease is the leading cause of death worldwide. The accumulation of wax substances (plaque) in the blood vessels restricts the normal blood flow. When the plaque severely narrows or blocks an artery, development of ischemic vascular disease (including stroke and heart attack) is inevitable. Researchers might be able to reverse the progression of these diseases by revascularization of the ischemic tissue. Revascularization is the process of new vessel growth, which could help the restoration of the blood flow in patients with ischemic vascular disease. One of the promising therapeutic strategies for revascularization is cell-based therapies. In cell-based approaches, a pool of healthy cells is isolated from the host tissue, expanded ex vivo and ultimately delivered into the ischemic area. However, administration of the cells to the ischemic tissue is challenging and often results in off-target distribution and low survival of transplanted cells. To address these challenges, researchers from the University of California Davis in United States of America and the University of Sao Paulo in Brazil collaborated to develop hydrogel systems for controlled in-situ delivery of cells [Campbell et. al. Biomaterials (2018), doi:10.1016/j.biomaterials.2018.06.038]. Their approach involves embedding cells in a hydrogel matrix to promote cell survival and retention during the administration of cells to the targeted tissue. For this study, the researchers used outgrowth endothelial cells (OECs). OECs are progenitor cells that can differentiate into a specific cell and have the potential to promote vascularization. However, apart from the choice of cells, the materials also matter. They built the hydrogel system with alginate. Alginate is a naturally occurring, biocompatible polymer, which has FDA approval for some clinical applications. Alginate hydrogels have a very small pore size (nanoporous) structure. However, to enable cell migration from the hydrogel, alginate degradation is necessary to achieve a more porous structure. As mammalian cells do not produce an enzyme to degrade alginate, the team loaded the alginate hydrogel with alginate lyase, an enzyme which breaks down the alginate chains, to enable hydrogel remodeling to facilitate the desired cell migration. The group studied the effect of the enzyme concentration on the hydrogel mechanical properties, pore size as well as cell migration. They studied the capability of new blood vessel formation on an in vivo chicken egg assay (chick chorioallantoic membrane (CAM) assay). The chick embryo is surrounded by highly vascularized extraembryonic membrane. When they implanted their hydrogel on the extraembryonic membrane of the developing chick egg, the cells were able to interact with the developing CAM environment when delivered from enzyme-loaded hydrogels and promoted new vessel formation. According to the researchers, the enzyme-loaded hydrogels are very promising for OEC delivery and could also be a great benefit for other cell-based therapies. Currently this cell delivery platform is being validated and tested in the context of lymphangiogenesis (the formation of new lymphatic vessels). Specifically, lymphatic endothelial progenitor cells will be imbedded within this material system and implanted on a murine animal model that mimics a human ischemic vascular disease.