Multifunctional Synthetic Microgels as Scaffolds to Control Protein-Cell Interactions and Extracellular Matrix Heterogeneity on the Nanoscale
Biomaterials
Final Report Abstract
The project aimed at the encapsulation of stem cells into synthetic multifunctional microgels that can mimic the extracellular matrix (ECM) to precisely control and fundamentally understand cell–matrix and cell–ligand interactions. As a material toolkit for this purpose, a set of multi-arm poly(ethylene glycols) (PEGs) that bear cyclooctyne as well as azide groups have been successfully prepared. These precursor polymers have been crosslinked by the strain-promoted azide–alkyne cycloaddition to prepare hydrogels. The polymer network topology in terms of the heterogeneity on the nanoscale could be controlled by using multi-arm PEGs of four and eight arms, as shown by rheological and static light scattering measurements. By using droplet microfluidic templating, single-cell-laden microgels have been prepared with effective control of their monodispersity, particle size, and the polymer network topology. For cell adhesion, RGD peptide sequences could be attached to the precursor polymers and incorporated into the microgel matrix. The initial viability of encapsulated D1 mesenchymal stem cells was observed to be 85–90%, but after one week of encapsulation it decreased down to 30%. For using this polymer construction kit for detailed investigations of the effects of network topology on stem cell fate, the long-term cell viability needs to be further improved in future work.