Spatial and Temporal Control of Stem Cell Behavior in 3D Sequentially Crosslinked Macroporous Hydrogels

The effect of matrix mechanics on stem cell behavior has received considerable attention due to the implications of tissue mechanics as not only a consequence but also a contributor to the development of certain pathologies. For example, a significant increase in matrix mechanics (“tissue stiffening”) is a hallmark of post-myocardial infarction [1], as well as heart valve calcification [2]. Recently, human mesenchymal stem cells (hMSCs) have been implemented in post-infarct therapeutic strategies due to their potential ability to contribute to tissue healing through differentiation and trophic factor secretion. However, due to aberrant mechanics and other microenvironment cues, studies have reported deleterious effects of hMSC implantation, such as ectopic calcification [3], which agrees well with previous reports on hMSC differentiation in response to mechanics [4]. Although not as well documented as stem cell differentiation in response to mechanics, there has been some initial evidence in support of the influence of mechanics on stem cell trophic factor secretion [5].