Alginate hydrogels of varied molecular weight distribution enable sustained release of sphingosine-1-phosphate and promote angiogenesis.

Alginate hydrogels have been widely validated for controlled release of growth factors and cytokines, but studies exploring sustained release of small hydrophobic lipids are lacking. Sphingosine-1-phosphate (S1P), a bioactive lipid, is an appealing small molecule for inducing blood vessel formation in the context of ischemic conditions. However, there are numerous biological and engineering challenges associated with designing biomaterial systems for controlled release of this lipid. Thus, the objective of this study was to design an injectable, alginate hydrogel formulation that provides controlled release of S1P to establish locally sustained concentration gradients that promote neovascularization. Herein, we varied the molecular weight distribution of alginate polymers within the hydrogel to alter the resultant mechanical properties in a manner that provides control over S1P release. With increasing high molecular weight (HMW) content, the hydrogels exhibited stiffer material properties and released S1P at slower rates. Accordingly, S1P released from hydrogels with 100% HMW content led to enhanced directed migration of outgrowth endothelial cells and blood vessel development assessed using a chick chorioallantoic membrane assay as compared to hydrogels with less HMW content. Overall, this study describes how alginate hydrogels of varied molecular weight may be used to control S1P release kinetics for therapeutic applications.