Small molecule functional groups for the controlled differentiation of human mesenchymal stem cells encapsulated in poly(ethylene glycol) hydrogels

摘要

Cell-matrix interactions play critical roles in regeneration, development, and disease. The work presented here demonstrates that encapsulated human mesenchymal stem cells (hMSCs) can be induced to differentiate down osteogenic and adipogenic pathways by controlling their 3D environment using tethered small molecule chemical functional groups. Hydrogels were formed using sufficiently low concentrations of tether molecules to maintain constant physical characteristics, encapsulation of hMSCs in 3D prevented changes in cell morphology, and hMSCs were shown to differentiate in normal growth media, indicating that the small-molecule functional groups induced differentiation. To our knowledge, this is the first example where synthetic matrices are shown to control induction of multiple hMSC lineages purely through interactions with small molecule chemical functional groups tethered to the hydrogel material. Strategies utilizing simple chemistry to control complex biological processes would be particularly are powerful as they could make production of therapeutic materials simpler, cheaper, and more easily controlled.