Colloidal Gels for Guiding Endothelial Cell Organization via Microstructural Morphology

One of the fundamental challenges in vascular morphogenesis is to understand how the microstructural morphology of a 3D matrix can provide the spatial cues to organize the endothelial cells (ECs) into specific vascular structures. Colloidal gels can provide well-controlled distinct morphological matrices because these gels are formed by the aggregation of particles. By altering the aggregation mode, the spatial organization of the particles can be controlled to yield different microstructural morphology. To demonstrate this, colloidal aggregates and gels were developed by electrostatic interaction-mediated aggregation of cationic polyurethane (PU) colloidal particles by using low molecular weight electrolyte and polyelectrolyte to develop microstructurally different colloidal gels without altering their bulk elasticity. Compact dense colloidal aggregates with constricted voids were developed via electrolyte-mediated aggregation, whereas stranded branched networks with interconnected voids were formed via polyelectrolyte-mediated bridging interactions. Results show that the microstructure of aggregated colloids and gels can regulate EC organizations. Within endothelial matrices, ECs track the microstructure of particulate phase to interconnect with stranded colloidal network but cluster around compact colloidal aggregate. Similarly, in colloidal gels, ECs formed capillary-like structures by interconnecting along the stranded networks with enhanced cell-matrix interactions and increased cell extension but aggregated within the constricted voids of compact dense gel with enhanced cell-cell interaction. Both morphometric analysis and expression of EC markers corroborated the cell organizations in these gels. Using these colloidal gels, we demonstrated the role of 3D microstructural morphology as an important regulator for spatial guidance of ECs and simultaneously established the significance of colloidal gels as 3D matrix to regulate cellular morphogenesis.