Multifunctional Synthetic Microgels as Scaffolds to Control Protein-Cell Interactions and Extracellular Matrix Heterogeneity on the Nanoscale

• Applicant: Dr. Torsten Rossow
• Subject Area: Polymer Materials ; Biomaterials
• Term: from 2015 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 279360998

The proposed project aims 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, cell-ligand, and cell-cell interactions. As a material platform for this purpose, I propose to prepare and use multi-arm poly(ethylene glycols) (PEGs) that bear cyclooctyne as well as azide groups. These precursor polymers can be crosslinked by the cytocompatible strain-promoted azide-alkyne cycloaddition in the presence of living cells thereby encapsulating them. By combining this crosslinking chemistry with droplet-based microfluidics, single-cell-laden microgels can be prepared with effective control of their monodispersity, particle size, and the polymer network topology. The latter aspect can be addressed by using multi-arm PEGs of a different number (four and eight) and length of arms, thereby controlling the heterogeneity as well as the network mesh size on the nanoscale. Those of the polymer arms that are not crucially needed for the network formation can be modified with cell adhesive ligands, growth factors or further functional groups. For this purpose, tetra- and octa-arm PEGs are chosen, respectively; as a result the ligand presentation can be controlled on the nanoscale, too. This modular material toolkit allows for studying the influence of extracellular matrix environments on stem cell differentiation, spreading, and proliferation with unprecedented consistency. Moreover, the use of microgel particles allows for the investigation of cell-cell interactions by assembling single-cell-laden microgels to larger 3D constructs. By this means, highly functional tissues that contain different cell types can be build up. Based hereon, I envisage to develop an in-vitro model for hematopoiesis to explore the influence of mesenchymal and hematopoietic stem cells as well as vascular cells and osteoblasts on the hematopoietic stem cell niche.

• DFG Programme: Research Fellowships
• International Connection: USA
• Participating Institution: Harvard University ; Harvard School of Engineering and Applied Sciences
• Host: Professor David Mooney, Ph.D.