Statement of Purpose: Cell-based therapies represent a promising solution to a myriad of diseases and conditions. However, the rapid and dramatic loss of cells upon injection into the target site remains a key bottleneck, severely stunting the promise of this approach. Mesenchymal stem cells (MSCs) are broadly studied for use in cell therapies due to their potential for autologous use and secretion of bioactive factors that stimulate tissue regeneration. The therapeutic potential and viability of MSCs can be enhanced by aggregating the cells into spheroids and transplantation using engineered materials such as alginate. Compared to monodisperse cells, MSC spheroids secrete increased quantities of potent growth factors. Unfortunately, even as spheroids, the bioactive nature of the MSC secretome is diminished by cell death or differentiation once implanted. We propose that the inclusion of sulfate groups within an alginate hydrogel would sequester endogenous biomolecules secreted by entrapped MSC spheroids, thereby prolonging the therapeutic effect of MSCs by presenting these factors to neighboring responsive cells. In this way, implanted MSCs can migrate out of the spheroid, differentiate, or even die, and their therapeutic secretome will remain to augment the healing microenvironment. In these studies, we hypothesized that the biophysical properties of alginate gels would be influenced by the degree of sulfation and method of crosslinking.