Polyurethane Microgel Based Microtissue: Interface-Guided Assembly and Spreading.

Colloidal gels are three-dimensional networks of microgel particles and can be utilized to design microtissues where the differential adhesive interactions between the particles and cells, guided by their surface energetics, are engineered to spatially assemble the cellular and colloidal components into three-dimensional microtissues. In this work we utilized a colloidal interaction approach to design cell-polyurethane (PU) microgel bimodal microtissues using endothelial cells (ECs) as a normal cell model and a nonmalignant breast cancer cell line (MCF-7) as a cancer cell model. PU microgels were developed from a library of segmental polyurethanes with poly(ethylene glycol) soft segment and aliphatic diisocyanate/l-tyrosine based chain extender as hard segment to modulate the interactions between PU colloidal particles and cells. The surface energies of the microgel particles and cells were estimated using Zisman's critical surface tension and van Oss-Good-Chaudhury theory (vOGCT) from liquid contact angle analysis. Binary interaction potentials between colloidal PU particles and cells and the ternary interaction between colloidal PU particle, cell, and collagen I/Matrigel were calculated to explain the formation of microtissues and their spreading in extraneous biomatrix respectively by using classical and extended DLVO theory (XDLVO). Furthermore, rheological analysis and in silico simulations were used to analyze the assembly and spreading of the PU microgel based microtissues. In vitro experiments showed that ECs and MCF-7 displayed more differentiated (EC spreading/MCF-7 lumen formation) character when mixed with microgel particles that were stable in aqueous medium and more undifferentiated character (EC nonspreading/MCF-7 spreading) when mixed with microgel particles unstable in aqueous medium.